NEWSLINE SNMMI Hosts FDA Workshop

n February 21, SNMMI and the U.S. Food and Drug Administration (FDA), Technology OAlliance, and World Molecular Imaging Society hosted ‘‘PET Drugs: A Workshop on Inspections Manage- ment and Regulatory Issues,’’ at the FDA White Oak Con- ference Center in Silver Spring, MD. The purpose of the workshop was to provide a forum for exchange of information and perspectives on the regulatory and compliance frame- work for PET drug manufacturing and thereby improve global understanding of PET drug manufacturing. The work- shop organizers included Sue Bunning, MA (MITA), Dalton Clark (SNMMI), Steve Mattmuller, MS, RPh (Kettering Medical Center), Sally Schwarz, MS (Washington Univer- sity), Henry VanBrocklin, PhD (University of California San Francisco), and Steve Zigler, PhD (PETNET Solutions). The At the Workshop on PET Drug Manufacturing: Sue Bunning, MS, Steve Zigler, PhD, Sally Shwarz, MS, Steve Mattmuller, workshop was attended by approximately 150 members of MS, RPh. the PET community and the FDA. Among the specific goals and objectives of the 1-day meeting were to: discuss regulatory compliance for devel- focused on lifecycle management of PET drug applications, opment and manufacturing of PET drugs and pathways for including management of PET drug applications (NDA drug applications, application maintenance, and inspections or ANDA), and PET community perspectives on PET drug based on Code of Federal Regulations Part 212 (Current application, with a follow-up discussion and question Good Manufacturing Practice [cGMP] for Emission period. After lunch, the third session looked at chemistry Tomography Drugs); share perspectives from industry, acade- and product quality assurance, including the microbiolog- mia, investigators, and regulators on inspection findings and ical regulatory perspective; product quality and sterility trends; and provide information on the management of Part 212 assurance; and chemistry and product quality assurance. inspections and maintenance of PET New Drug Applications The final session covered the changing landscape of PET (NDAs) and Abbreviated New Drug Applications (ANDAs). drugs, labeling requirements for NDAs, and requirements The workshop included 4 sessions, each co-moderated by an for electronic filing of regulatory applications. FDA staff member and a member of the PET community. The Themes stressed throughout the workshop included: speakers included representatives of PET drug manufacturers the need for uniformity in FDA inspections of PET drug from academia, industry, as well as the FDA. establishments, a consensus on a science-based risk profile The first session looked at considerations and trends in for PET drugs, improvements to training for FDA investi- inspections and compliance, including manufacturing pro- gators and the regulated community, and the need for cess assessment and preapproval inspections, and recent continued dialog between the FDA and PET drug stake- experience with PET surveillance cGMP inspections of holders. The organizers plan to make slides from the work- PET manufacturers; and current trends and observations on shop available to the public and are also planning a follow-up inspections and PET surveillance inspections through the session at the upcoming SNMMI annual meeting in New FDA pilot program for tablet-based inspections for PET drugs. Orleans, LA. A panel discussion and questions followed. The second session SNMMI

Newsline 11N SNMMI at NRC Commissioners’ Meeting

n January 28 at a Commissioners’ Meeting of the Nuclear Regulatory Commission (NRC) in Rockville, MD, SNMMI NEWSLINE OPresident Vasken Dilsizian, MD, and patient advocate Josh Mailman provided their perspectives on recent NRC staff initiatives related to medical uses of radioactive materials. The meeting was organized into 2 panels: 1 featuring NRC staff and 1 with stake- holders from the medical community who use or have patient perspectives on radioactive materials. Five presenters in each panel gave 8-minute presentations. For the NRC staff, these included an overview of the NRC program for medical uses of radioactive materials, the status of recent NRC staff activities, innovation op- portunities and initiatives, efforts to prepare for review of emerging medical technologies, and regional perspectives on licensing and oversight of medical licensees. The external stakeholder panel At the January 28 NRC Commissioners’ Meeting, from left: addressed emerging issues in the national program for regulation Commissioner Jeff Baran; Commissioner Annie Caputo; of medical uses of radioactive materials, medical community American Society for Oncology President Thomas suggestions about transformation/innovation opportunities, per- Eichler, MD; patient advocate Josh Mailman; NRC Chair spectives on recent NRC staff initiatives related to medical uses Kristine L. Svinicki; SNMMI President Vasken Dilsizian, of radioactive materials, and patient suggestions for transforma- MD; and Commissioner David A. Wright. tion/innovation and opportunities for the NRC to explore. These presentations were followed by an extended period in which NRC Mailman was the only patient to sit on a panel. In his presentation, commissioners asked questions and followed up on the panelists’ he offered views as an ‘‘end user’’ of medical radioactive materials. His comments. focus was on treatment of neuroendocrine tumors, and he echoed In his remarks, Dilsizian highlighted the importance of appro- Dilsizian’s concerns about training and education requirements. A priate training and experience requirements for authorized users, complete transcript of the meeting and panelists’ slides are available at: addressed concerns about patient safety and patient release https://www.nrc.gov/reading-rm/doc-collections/commission/tr/2020/. materials and guidelines after treatment with radioactive materials, Nuclear Regulatory Commission and described potential barriers to patient access. SNMMI

Congressional Briefing: Diagnostic Imaging and Alzheimer Disease

SNMMI, the Council on Radionuclides and Radiopharma- Klunk, coinventor of the first amyloid imaging radiotracer, ceuticals, and the Medical Imaging Technology Alliance cohosted on Pittsburgh compound-B, discussed the history of amyloid PET scans January 29 a Capitol Hill congressional briefing on ‘‘A New and their role in diagnosis and development of treatment plans. ‘‘Rel- Hope: Advancements in Diagnostic Imaging and Alzheimer’s.’’ ative to past diagnostic approaches, amyloid PET scans allow us to The briefing was an opportunity for physicians, patients, and industry track disease progression in a way that is clear and striking,’’ he said. representatives to talk with congressional representatives and staff about ‘‘Put in simpler terms, these tools are shining a light on important the growing importance of access to diagnostic radiopharmaceuti- dimensions of the disease that were previously unclear.’’ cals—in particular, those for amyloid PET imaging for diagnosis, re- Dent spoke about the importance of amyloid PET imaging in search, and treatment in Alzheimer disease (AD). Event speakers AD drug development. ‘‘Amyloid imaging is used to select the right also addressed the need for fair payment for radiopharmaceuticals and patients for clinical trials,’’ he said. ‘‘It may be critical for patient passage of the Medicare Diagnostic Radiopharmaceutical Payment identification when therapies enter the market, and patients can ben- Equity Act of 2019 (HR 3772). efit from new therapies only if infrastructure issues are addressed and Speakers included AD patient and caregiver team Geri and appropriate reimbursement is in place.’’ Jim Taylor; William Klunk, MD, PhD, codirector of the University Members of the community who would like of Pittsburgh (PA) Alzheimer’s Disease Research Center; and Gersham to express their support for ensuring patient access to lifesaving Dent, PhD, MBA, senior director of clinical imaging at Biogen diagnostic radiopharmaceutical can go to: https://snmmi.quorum.us/ (Cambridge, MA). Congressman Bobby Rush (D-IL), one of the orig- campaign/23260/ to write to their Congressional representatives. inal cosponsors of HR 3772, attended to voice his support for the bill. SNMMI

12N THE JOURNAL OF NUCLEAR MEDICINE • Vol. 61 • No. 4 • April 2020 NEWSLINE Future Leaders of SNMMI and SNMMI-TS

uring the SNMMI 2020 Mid-Winter Meeting in Tampa, Menendez, DVM, PhD; Domnique Newallo, MD, RT (R) FL, in January, SNMMI and SNMMI-Technologist CT); Thomas Ng, MD, PhD; Daniella Pinho, MD; Ali DSection (SNMMI-TS) held leadership academies. Salavati, MD, MPH; and Vanessa Sanders, PhD. These academies are open to physicians, scientists, and tech- nologists with strong leadership abilities who are inter- SNMMI-TS Leadership Academy ested in taking more active roles in the societies, as well SNMMI-TS graduated its 13th class of its Leadership as within the nuclear medicine and molecular imaging Academy during the National Council of Representatives community. meeting on January 24. Long-time facilitator Shawn Dun- ning from Adventure Associates and SNMMI-TS leadership, SNMMI Future Leaders Academy including President Mark Crosthwaite, CNMT, led a day of On January 25, during the House of Delegates meeting, lessons, team-building activities, and networking ses- SNMMI recognized the graduates of its 5th Future Leaders sions to build personal skills while promoting SNMMI-TS Academy. The academy was facilitated by Jon Burroughs, leadership opportunities. Participants included practicing MD, MBA, with the American Association for Physician nuclear medicine technologists, student attendees, and staff Leadership, and included the opportunity to engage with representatives. SNMMI-TS President Elect Tina Buehner, current and past SNMMI leaders. The academy leadership MS, CNMT, NMTCB(CT)(RS), RT(N)(CT), noted that she development workshop focused on ways to guide success- looks forward to seeing these graduates on future SNMMI- ful efforts in health care transformation, conflict resolution, TS committees to continue their involvement with the and strategic planning and on the future of the field and society. SNMMI’s role in this evolution. Participants were then in- The 14 graduates of the SNMMI-TS Leadership Academy vited to various SNMMI governance events throughout the Class of 2020 were Roberta Alvarez, MS, ARRT(N)(MR); Mid-Winter Meeting to see first-hand the organizational Garrett Anderson; Dalton Clark; Rebecca Gallagher; Jane structure of the society. Kamm; Nicole LaBrecque; Jose Meza, CNMT, PET, NCT, The 12 graduates of the Future Leaders Academy Class RT(N); Samantha Miller, RT(N); Keexia Osborne; Christopher of 2020 were Yoram Baum, MD; Sarah Cheal, PhD; Shadi Owens, CNMT, PET, RT(R)(CT)(MR)(N); Kait Solomon, Esfahani, MD, MPH; Pedram Heidari, MD, MPH; Mary MPS; Taylor Steenburgen; Laura Wotta, CNMT; and Thalia Ellen Koran, MD, PhD; Courtney Lawhn-Heath, MD; Maria Zolis.

2020 SNMMI Future Leaders Academy graduates and so- 2020 SNMMI-TS Leadership Academy graduates and so- ciety leadership at the SNMMI Mid-Winter Meeting. ciety leadership at the SNMMI Mid-Winter Meeting.

Newsline 13N SNMMI LEADERSHIP UPDATE

To the SNMMI-TS: Congratulations on 50 Years of NEWSLINE Dedicated Service to SNMMI and Your Patients

Vasken Dilsizian, MD, SNMMI President

n behalf of the senior leadership of the Society, I would like to express our heartfelt congratulations Oto the nuclear medicine technologists for their his- toric 50th anniversary celebrations as dedicated members of the Society of Nuclear Medicine and Molecular Imaging– Technologist Section (SNMMI-TS). We are grateful for your passionate commitment to and enthusiasm for the field of nuclear medicine. To improve the human condition through imaging and image-guided therapy is the heart of SNMMI’s mission. The honorable profession that you have chosen, partnering with nuclear medicine physicians to de- liver the highest quality of images and care to our patients, is perhaps the highest calling of all. Your compassionate care changes the lives of patients every day, and we are grateful for all of your efforts. On this festive occasion, I would like to recognize the seminal contributions of nuclear medicine technologists to Vasken Dilsizian, MD the advancement of science and direct care of patients. When reviewing historical discoveries, it becomes clear The strength and merit of our scientific publications are that many of the remarkable achievements in the field were laudable, but we must recognize and give credit to the other the result of close collaboration between nuclear medicine pivotal components of our professions that may signifi- physicians and technologists. For example, the imaging cantly influence health care delivery. We must pay attention parameters for the rectilinear scanner, the technical details to our patients’ perspectives, education, and fears in the of tracer injection, and the imaging of stress myocardial context of understanding their concerns about longevity and perfusion with 43K were developed through close collabo- health. With this in mind, our nuclear medicine technologists ration between chief nuclear medicine technologists and have played a pivotal role as the ‘‘face’’ of our profession, nuclear medicine physicians. having direct access to our patients during the busy clinic day. Through 50 years of collaboration we have charted new paths, reached across disciplines, built consensus, and overcome roadblocks to deliver the best of care to our patients. We have appreciated the importance of exploiting the radiotracer principles for understanding human physiology and biochemistry and, thereby, improving the diagnosis and treatment of disease. Recent advances in molecular-targeted radiopharmaceutical therapy will undoubtedly further trans- form our field by extending healthy lives, an achievement of which we can all be proud. Congratulations to the SNMMI-TS for achieving this major milestone! Together, we have come far. But, as in The SNMMI-Technologist most of our endeavors, we have a long way to go. I am confident Section is celebrating its 50th that our journey will become more noble and altruistic in the year in 2020. years to come.

14N THE JOURNAL OF NUCLEAR MEDICINE • Vol. 61 • No. 4 • April 2020 NEWSLINE

NEWSBRIEFS

Ngai named Director of NIH IAEA and Dose Projection for or project the dose received by the public, BRAIN Initiative Radiologic Emergencies among many other projections. National Institutes of Health (NIH) In a press release issued on February The CRP will use findings from Director Francis S. Collins, MD, PhD, 13, the International Atomic Energy these discussions to help IAEA Member announced on January 29 the selection Agency (IAEA) reviewed presentations States better understand the advantages of John J. Ngai, PhD, as director of the and discussions for its first research and limitations of using dose pro- NIH Brain Research through Advancing coordination meeting on using dose jection tools, including uncertainties Innovative Neurotechnologies (BRAIN) projection tools in nuclear or radiologic associated with modeling and varia- tions in implementation of different Initiative. Until joining NIH in March, emergencies. Participants in the meeting, models by different sites. At the meeting, Ngai was the Coates Family Professor held at the IAEA in Vienna, Austria, from experts considered reported experience of Neuroscience at the University of January 20 to 24, came from 21 countries from the use of dose projection tools California, Berkeley. and 25 institutes to share their experience The NIH BRAIN Initiative is a and approaches in improving them. and knowledge about using dose pro- Their analysis will inform CRP recom- large-scale effort to accelerate neuro- jection tools when preparing for and science. Since its launch in 2013, the mendations to improve the tools’ ef- responding to such emergencies. ‘‘The fectiveness in supporting emergency initiative has funded hundreds of re- goal of this coordinated research project preparedness and response. search projects that have led to break- [CRP] is to outline the plans and details, International Atomic Energy throughs, including creation of a self- which will be implemented over the Agency tuning brain implant that could help next 3 years, to help improve the perfor- treat Parkinson disease, development mance of dose projection tools in the WHO Reports on Global Cancer of a computer program that can mimic preparedness and response to nuclear Burden natural speech from brain signals, and or radiological emergencies,’’ said Phillip The World Health Organization construction of a brain cell inventory. Vilar Welter, IAEA Emergency Pre- (WHO)onFebruary4releasedits BRAIN-funded researchers have also paredness Officer. International Agency for Research on shown the ability to make high-speed, Researchers, technical experts, and Cancer World Cancer Report: Cancer high-resolution, 3D films of functional observers attended the course organized Research for Cancer Prevention. In nervous system activity. by the IAEA Incident and Emergency addition to a separate report issued on ‘‘Recent technological and scien- Centre and IAEA Division of Radiation, the same day on current statistics and tific advances are transforming our un- Transport, and Waste Safety. Attendees findings on cancer, this report em- derstanding of the brain,’’ said Ngai. ‘‘I represented a broad range of organi- phasized the need to enhance cancer am deeply inspired by these advances zations, including national laboratories, services in low- and middle-income and look forward to my new role in public health organizations, and nuclear countries. WHO warned that, if current enabling BRAIN Initiative investiga- trends continue, the world will see a tors to unlock the secrets of the brain safety institutions. IAEA noted the importance of dose 60% increase in cancer cases over the and lay new foundations for treating next 2 decades, with the global cancer human brain disorders.’’ He will oversee projection tools in ensuring effective emergency preparedness and response. burden expected to reach 29 million the long-term strategy and day-to-day new cancer cases per year by 2040. The In the preparedness phase, tools such operations of the initiative as it takes greatest increase (an estimated 81%) in as the Real-time On-line Decision Sup- on the challenges of the next 5-year new cases will occur in low- and middle- port system (RODOS) or the MELCOR plan, announced in fall 2019. Congress income countries, where survival rates Accident Consequence Code System has consistently supported BRAIN are currently lowest, with severely limited through the appropriations process and (MACCS) are used to assess the poten- resources focused on urgent needs in the 21st Century Cures Act. tial radiologic consequences of an event. combating infectious diseases and im- ‘‘Dr. Ngai’s appointment marks a These projections can help authorities proving maternal and child health. In new chapter in the BRAIN Initiative,’’ develop emergency plans that specifically 2019, more than 90% of high-income said Walter J. Koroshetz, MD, director address the expected consequences. countries reported that comprehensive of NIH’s National Institute of Neuro- For example, these tools can be used treatment services for cancer were avail- logical Disorders and . ‘‘He will to determine the size of emergency plan- able in the public health system compared provide the initiative and the clear vision ning zones needed for protective ac- to less than 15% of low-income countries. the project needs to navigate through tions, prioritize locations for radiation ‘‘This is a wake-up call to all of us this critical period.’’ monitoring, estimate the location and to tackle the unacceptable inequalities National Institutes of Health type of contamination on the ground, between cancer services in rich and

Newsline 15N poor countries,’’ said Ren Minghui, other criminal activities. The data, sub- and 2 included . MD, PhD, Assistant Director General, mitted to the IAEA Incident and Traf- Radioactive sources continue to be Universal Health Coverage/Communi- ficking Database (ITDB) by countries reported as stolen or missing, under- cable and Noncommunicable Diseases, on a voluntary basis, was highlighted in scoring the need to improve security WHO. ‘‘If people have access to primary an annual fact sheet published during measures for such sources, especially

NEWSLINE care and referral systems then cancer can the February IAEA ministerial confer- during transport. be detected early, treated effectively, and ence on strengthening nuclear security Attendees at the IAEA conference cured. Cancer should not be a death and countering the threat of nuclear adopted a declaration to enhance global sentence for anyone, anywhere.’’ terrorism. With 140 participating States, nuclear security, including a specific ‘‘At least 7 million lives could be the database fosters international cooper- commitment ‘‘to combatting illicit traf- saved over the next decade by identi- ation and information sharing among ficking of nuclear and other radioactive fying the most appropriate science for countries. The data are shared with the material and to ensure that the material each country situation, by basing strong IAEA, other Member States, and relevant cannot be used by non-State actors for cancer responses on universal health international organizations supporting the malicious purposes.’’ The related fact coverage, and by mobilizing different retrieval of lost or stolen material and sheet is available at: https://www.iaea. stakeholders to work together,’’ said the prosecution of suspected criminals. org/sites/default/files/20/02/itdb-factsheet- Tedros Adhanom Ghebreyesus, PhD, ‘‘As a unique asset in the IAEA’s 2020.pdf MSc, Director General, WHO. work to strengthen nuclear security, the International Atomic Energy The WHO report highlighted a wide ITDB allows us to identify threats and Agency range of proven interventions to prevent trends so that we can support our Member new cancer cases. These include con- States in improving the implementation FDA Electronic Formats for trolling tobacco use (responsible for 25% of their nuclear security commitments,’’ Pharmaceutical Submissions of cancer deaths), vaccinating against said Raja Raja Adnan, Director of the hepatitis B to prevent liver cancer, IAEA Division of Nuclear Security. On February 24 the U.S. Food and eliminating cervical cancer by vac- In 2019, 189 incidents were re- Drug Administration (FDA) issued spec- cinating against human papilloma ported by 36 States, indicating that ifications for electronic formats for sub- virus, enhancing screening and treatment, unauthorized activities and events in- missions to the agency. The document, Providing Regulatory Submissions implementing high-impact cancer man- volving nuclear and other radioactive titled in Electronic Format: Certain Human agement interventions that bring value for material, including incidents of traffick- Pharmaceutical Product Applications and money, and ensuring access to palliative ing and malicious use, continue to occur. care, including pain relief. Related Submissions Using the eCTD Six of the incidents were related to The complete report is available Specifications. Guidance for Industry trafficking or malicious use, continuing ,de- for download at https://shop.iarc.fr/ a slight downward trend since a peak of scribes how sponsors and applicants must products/world-cancer-report-cancer- 20 such incidents around 2005. For the organize electronic content submitted to research-for-cancer-prevention-pdf. FDA for all submission types under section World Health Organization other 183 incidents, either insufficient information was available to determine 745A(a) of the Food, Drug, and Cosmetic Database Documents Loss of any connection with trafficking or mali- Act. The guidance also references several Radioactive Material cious use or sufficient information was technical specification documents and the Electronic Common Technical Document The International Atomic Energy available to rule out criminal activity. Agency (IAEA; Vienna, Austria) in 2019 Since 1993, 3,686 incidents have Conformance (eCTD) Guide,which received notifications of nearly 190 in- been reported to the ITDB, of which provide additional details about organi- cidents of nuclear and other radioactive 290 involved a confirmed or likely act zation of content. The final document material being out of regulatory control, of trafficking or malicious use. Twelve is available at https://www.fda.gov/media/ including some cases of trafficking and of those incidents included high-enriched 135373/download.

FROM THE LITERATURE

Each month the editor of Newsline and journals. These briefs are sometimes blurred, as radiola- selects articles on diagnostic, therapeu- are offered as a monthly window on bels are increasingly used as adjuncts tic, research, and practice issues from the broad arena of medical and scien- to therapy and/or as active agents in a range of international publications. tific endeavor in which nuclear medi- therapeutic regimens, and these shifting Most selections come from outside the cine now plays an essential role. The lines are reflected in the briefs presented standard canon of nuclear medicine lines between diagnosis and therapy here.

16N THE JOURNAL OF NUCLEAR MEDICINE • Vol. 61 • No. 4 • April 2020 NEWSLINE

Guidelines for Publishing PET agement in patients with biochemical trol methodology. For the Measure and Brain Data recurrent prostate cancer. The study in- Improve phases, 5 technologists moni- In an article published online on cluded 104 men at multiple institutions tored quality in 263 injections with a February 16 ahead of print in the with a first episode of biochemical re- 13.3% infiltration rate. In the Improve Journal of Cerebral Flow and currence after curative-intent primary phase, after implementation of a qual- Metabolism, experts from more than therapy. Patients underwent 18F-fluciclo- ity improvement plan, the same tech- 25 PET centers around the world de- vine PET/CT, with management plans nologists monitored 278 injections tailed the results of a consensus effort documented before and after imag- with a 2.9% infiltration rate. In the Con- to standardize the organization and ing. Changes to the planned treatment trol phase, 7 new technologists were added sharing of PET neuroimaging data. modality were classified as major and and the resulting group of 12 monitored The authors recommended publish- those within treatment modality as mi- 1,240 injections with a 3.1% infiltra- ing standards for tracer characteristics, nor. Additional data included identi- tion rate. The 7 added technologists had image acquisition, image preprocess- fication of optimal prostate-specific significantly higher infiltration rates. ing, and outcomes estimation for PET antigen (PSA) thresholds for disease The authors concluded that a quality studies. Reporting information was detection, salvage treatment outcomes improvement plan ‘‘can significantly im- classified as mandatory, recommended, as assessed by PET, and overall safety. prove and sustain injection quality; or optional. They also presented a When lesions were identified on PET however, ongoing monitoring is needed framework for data archiving and sharing (56 lesions; 56% of patients), about 33% as new technologists join the team.’’ within and across centers and insti- were positive at PSA levels #1ng/mL JCO Oncology Practice tutions. Special note was made that and 93% were positive at PSA levels ‘‘because of the high cost of PET .2.0ngmL.Afterimaging,66patients Postadjuvant Therapy neuroimaging studies, sample sizes tend (64%) were assigned changes in man- PET/CT in Oral SCC to be small and relatively few sites agement, with 43 of these defined as Qian et al. from the Winship Can- worldwide have the required multidis- major: 16 (24%) from salvage or sys- cer Institute of Emory University and ciplinary expertise to properly conduct temic therapy to watchful waiting (16/ Emory University School of Medicine and analyze PET studies.’’ Encourage- 66; 24%); 16 from salvage therapy to (Atlanta, GA) reported on February ment of data sharing and agreed-upon systemic therapy (24%); and 11 (17%) 14 in Laryngoscope on a study of methods to standardize such data will to changes in treatment modality. The the outcomes and predictive value of enable the aggregation of multiple remaining 23 patients with manage- 3-mo postadjuvant therapy PET/CT datasets to create large sample sizes ment changes saw their preimaging in patients with locally advanced oral with stronger statistical power than plans modified, 22 by adjustments to squamous cell carcinoma. The study in- is currently possible across dispa- planned /radiotherapy to cluded 220 patients with stage III, rate sites. include a 18F-fluciclovine–guided boost. IVA, or IVB disease who had under- Journal of Cerebral Blood Flow Where 18F-fluciclovine guided salvage gone resection and adjuvant radiation and Metabolism therapy, the PSA response rate was or chemoradiation therapy. PET/CT higher. The authors concluded that images were classified as suspicious 18F-Fluciclovine PET in ‘‘incorporating 18F-fluciclovine PET/ (primary or neck category $3ordis- Recurrent Prostate Cancer CT into treatment planning may opti- tant lesion present) or nonsuspicious. Scarsbrook et al. from the Leeds mize targeting of recurrence sites and Factors compared between the 2 groups Teaching Hospitals NHS Trust/Univer- avoid futile salvage therapy.’’ were locoregional and distant pro- sity of Leeds, Oxford University Hospi- International Journal of Radiation gression, overall survival, positive and tals NHS Foundation Trust, University Oncology, Biology, Physics negative predictive values of imaging, College London Hospitals, NHS Foun- sensitivity and specificity of imaging, dation Trust, the Royal Marsden NHS Quality Improvement for PET/ and success rates of salvage. Of the Foundation Trust (London), Mount CT Radiotracer Infiltrations 220 patients, 67 (30%) were found to Vernon Cancer Centre (London), In an article e-published on Feb- have lesions suspicious on imaging, and King’s College London and Guy’s & ruary 11 in JCO Oncology Practice, this was significantly associated with lo- St. Thomas’ Hospital (London), Gart- Kiser et al. from the Carilion Clinic cal and distant failure as well as poorer navel General Hospital (Glasgow), the (Roanoke, VA), the University of North overall survival. Positive predictive value, University of Glasgow, and Blue Earth Carolina (Chapel Hill), and Lucerno locoregional predictive value, negative Diagnostics (Oxford; all in the UK), Dynamics (Cary, NC) reported on a predictive value, sensitivity, and speci- representing the FALCON study group, study describing a quality improvement ficity of imaging were 85%, 79%, 73%, reported on February 14 ahead of print initiative aimed at assessing and reduc- 58%, and 92%, respectively. Thirty- in the International Journal of Radia- ing PET/CT radiotracer infiltration. The seven patients (65% of those with tion Oncology, Biology, Physics on the multicenter initiative used the Define, biopsy-confirmed progression) under- effect of 18F-fluciclovine PET on man- Measure, Analyze, Improve, and Con- went salvage therapy, and 4 (11%)

Newsline 17N showed no evidence of disease at last SPECT/CT in Critical Limb the value of SPECT/CT in identifying follow-up. The authors concluded that Ischemia pain generators. The retrospective study ‘‘for locally advanced oral squamous Chou et al. from Nationwide Child- included 190 (age, 58 6 13 y; 51% cell carcinoma, a PET/CT scan 3 months ren’s Hospital and The Ohio State Uni- men, 49% women) patients who had after adjuvant therapy is strongly predic- versity College of Medicine (both in undergone high-resolution 99Tc-methyl

NEWSLINE tive of disease recurrence and survival, Columbus, OH) reported on March 1 diphosphonate SPECT/CT for axial demonstrating improved performance in Advances in Wound Care (2020;9 neck or back pain assessment. Facet over postoperative imaging in previous [3]:103–111) on a single-patient study joints with increased tracer uptake were studies.’’ intended to evaluate the feasibility classified as hypermetabolic, and other Laryngoscope of serial radiotracer-based imaging for study imaging data included number, quantifying volumetric changes in mi- level, and laterality of hypermetabolic Perfusion PET Cardiac crovascular perfusion within angiosomes facets. Eighty-five patients (48%) showed Outcomes Predictors of the foot after lower extremity revascu- zygopophyseal joint hypermetabolism In an article e-published on February larization in the setting of critical limb (ZJH) on SPECT, with 202 hypermet- 13 in PloS One (2020;15(2):e0228931), ischemia (CLI). The researchers reported abolic facets identified (average num- Guerraty et al. from the University of on their experience with a 63-y-old ber of facets with ZJH, 2.38 6 1.91). Pennsylvania (Philadelphia) and Prairie man with CLI, type 2 diabetes melli- In patients with a positive scan, lumbar Cardiovascular (Belleville, IL) compared tus, and nonhealing foot ulcers of the facets were most commonly affected data from 82Rb PET cardiac imaging– first and second digits of the right (69% with ZJH), followed by the cer- assessed quantitative myocardial blood foot. The patient underwent 99mTc-tetro- vical (24%) and thoracic regions (6%). flow and flow reserve with traditional fosmin SPECT/CT perfusion imaging C1-2 and C2-3 (22% each with cervi- cardiac risk factors as prognostic bio- before and after clinically indicated re- cal ZJH) and L4-5 (32% with lumbar markers of adverse outcomes. The vascularization (balloon angioplasty of ZJH) were most often affected in the study included 1,283 participants (a the superficial femoral and popliteal cervical and lumbar regions, respec- diverse population, with 60% African arteries) of the lower extremity. The tively. The authors concluded that the American and 35.3% Caucasian) who authors found that quantitative im- finding that almost half of all patients underwent rest–dypyridamole stress provements in stenosis of the superfi- with axial neck or back pain showed 82Rb PET. Over a mean follow-up of cial femoral artery after surgery were ZJH on SPECT/CT supported ZJH sites 2.3 y, major adverse cardiovascular associated with angiosome-dependent as potential pain generators and targets events (unstable angina, non-ST and SPECT-assessed improvements in mi- for treatment. They added that ‘‘our ST-elevation myocardial infarction, crovascular foot perfusion. Serial changes results support the role for SPECT/ stroke, and death) were documented. in angiosome perfusion as assessed CT in the work-up of patients with axial Resting myocardial blood flow (1.1 6 by SPECT/CT were compared with quan- neck or back pain, which may reduce 0.4 mL/min/g) was found to be asso- titative changes in peripheral vascular invasive diagnostic procedures and aid ciated with adverse cardiovascular anatomy and hemodynamics, as assessed in treatment planning.’’ outcomes. Myocardial blood flow re- by standard clinical tools. The authors World Neurosurgery serve (2.1 6 0.8) was found to be concluded that ‘‘SPECT/CT imaging al- more independently and inversely as- lows for quantification of serial perfusion PET/CT Volumetric sociated with major adverse coronary changes within angiosomes containing events than were either traditional car- nonhealing ulcers and provides physio- Parameter Predictions in diovascular risk factors or perfusion logical assessment that is complementary Pancreatic Cancer defectsinregressionanalysis.Flowre- to conventional anatomical and hemody- Mohamed et al. from the Royal serve was also more strongly associated namic measures in the evaluation of lower Liverpool University Hospital, the with major adverse events than tradi- extremity revascularization.’’ Liverpool Cancer Research Centre, tional cardiovascular risk factors and Advances in Wound Care and the Mount Vernon Hospital (Mid- perfusion defects in regression analy- dlesex; all in the UK) reported on sis. A decision tree analysis confirmed SPECT/CT, Hypermetabolic February 7 ahead of print in the Euro- myocardial blood flow reserve as su- Facet ID, and Pain pean Journal of Surgical Oncology on a perior to established cardiovascular In an article e-published on Febru- study intended to determine the prog- risk factors in predicting outcomes. ary 11 in World Neurosurgery, Perez- nostic value of 18F-FDG PET/CT volu- The authors concluded that ‘‘incorporating Roman et al. from the University of metric parameters in survival prediction resting myocardial blood flow and Miami Miller School of Medicine in pancreatic cancer. The retrospective myocardial blood flow reserve in cor- (FL) reported on a study investigating study included 89 patients with pancre- onary artery disease assessment may the incidence of hypermetabolic fac- atic cancer who had undergone 18F- improve clinical decision making.’’ ets on SPECT/CT imaging in patients FDG PET/CT imaging. Imaging data PloS One with axial neck or back pain to explore collected included tumor SUVmax and

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SUVmean, metabolic tumor volume, and structured diagnostic approach facilitated land) reported on a study investigating total lesion glycolysis. The prognostic by the algorithm was determined to be correlations between 18F-sodium fluo- value of 18F-FDG PET/CT for overall useful by clinicians in the study in patient ride PET and histomorphometry survival was compared with that of clin- management in failing arthroplasties. The in the diagnosis of renal osteodystrophy. ical and pathology parameters. Median authors concluded that the algorithm The study included 26 patients on di- survival times for patients with high served as an effective tool, allowing up to alysis with biochemical abnormalities and low total lesion glycolysis ($55 20% of patients to avoid revision surgery. indicating mineral and bone disorder. and ,55) were 18 and 5 mo, respectively. Diagnostics (Basel) All patients underwent 18F-NaF PET TherespectivehighandlowSUVmean, imaging and a bone biopsy. Activity on metabolic tumor volume, and SUVmax 99mTc-HDP SPECT/CT in PET was measured in the lumbar spine survival times were 18 and 6 mo, 16 Cervicogenic Headache and at the anterior iliac crest. Dynamic and 6 mo, and 18 and 6 months. On Cho et al. from Ajou University and static parameters from the bone biopsy subsequent multivariate and subgroup College of Medicine (Suwon-si), Yonsei were assessed, using bone formation analysis, total lesion glycolysis was University College of Medicine (Seoul), rate per bone surface and activation identified as the only significant PET frequency per year as histomorphometric Cham Teun Research Institute (Seoul), metric, after adjusting for the presence markers. They identified a statistically and Hwalgichan Hospital (Ilsan-si, all of distant metastases. The authors con- significant correlation between fluoride in Korea) reported on February 2 ahead cluded that 18F-FDG PET/CT ‘‘is a useful activity on PET and multiple histo- of print in the Journal of Clinical Med- tool in the preoperative evaluation of pa- morphometric parameters. 18F-NaF icine on a study assessing the utility of tients with pancreatic cancer,’’ with tumor 99mTc-HDP SPECT/CT in diagnosing PETsensitivityandspecificityindif- total lesion glycolysis offering an inde- and guiding treatment in cervicogenic ferentiating low turnover from non– pendent prognostic value in both poten- headache. The retrospective study in- low turnover were 76% and 78%, tially operable and metastatic disease. respectively. The authors concluded cluded 23 patients diagnosed with cer- European Journal of Surgical that, on the basis of this strong corre- vicogenic headache who were divided Oncology lation, ‘‘18F-NaF PET may possibly be into 2 groups: those who had undergone a noninvasive diagnostic tool in dialy- SPECT/CT (n 5 11) and controls (n 5 Imaging-Guided Diagnostic sis patients with low-turnover bone dis- Algorithm for Joint 12). The SPECT/CT group was sub- divided into SPECT/CT-positive and ease, but further research is needed.’’ Replacement Complications Bone –negative finding groups. Individuals In an article e-published on Febru- in the SPECT/CT group received an ary 11 in Diagnostics (Basel),Khalid PET and/or PET/CT intraarticular injection at SPECT/CT– et al. from Aalborg University/Aalborg in Posttransplant verified lesion sites, and those in the con- University Hospital (Denmark) report- Lymphoproliferative Disorder trol group received third occipital nerve ed on a multidisciplinary diagnostic Ballova et al. from the Cantonal blocks. Patients were evaluated with a algorithm for evaluation of patients Hospital Baden (Switzerland), the Ente range of assessments at 1, 3, and 6 mo presenting with prosthetic hip or knee after this intervention. At 6 mo, individ- Ospedaliero Cantonale (Bellinzona, complications. The algorithm included uals in the SPECT/CT group scored Switzerland), the University of Bres- multimodal radionuclide imaging and lower on the visual analog scale, the neck cia and Spedali Civili Brescia (Italy), microbiologic analyses. A total of 156 Niguarda Hospital (Milan, Italy), the disability index, and the global perceived patients with 163 arthroplasties were Universit`a della Svizzera Italiana (Lugano, effect scale. More successful responders included in the study. When surgeons Switzerland), and the University of were in the SPECT/CT-positive group suspected prosthetic joint infection or Lausanne/Lausanne University Hos- at 6 mo than in the control group (75% aseptic failure, patients proceeded to pital (Switzerland) reported on Feb- and 0%, respectively). The authors con- Diagnostics (Basel) surgery. When the cause of pain was cluded that ‘‘SPECT/CT can identify ar- ruary12in on a not evident, imaging was scheduled with thritic changes and accurately define systematic review and metaanalysis 99Tc-HDP SPECT/CT, 111In-labeled of the published literature on the di- 99 therapeutic targets’’ in this disease setting. 18 white blood cells combined with Tc- Journal of Clinical Medicine agnostic performance of F-FDG nanocolloid SPECT/CT, PET and/or 18F-FDG PET/CT in detec- and 18F-FDG PET/CT. A total of 118 tion of posttransplant lymphoproliferative revision surgeries were performed in 18F-NaF PET and Bone disorder. Five published articles met 112 patients (71 for aseptic failure Histomorphometry in Dialysis the review criteria, with a total of 336 and 41 for revision of prosthetic joint In an article e-published on Feb- transplant recipients. Analysis showed infection). Fifty-five patients underwent ruary 10 in Bone, Aaltonen et al. from that the pooled sensitivity and specific- radionuclide imaging. Thirty-four patients the Turku University Hospital/Univer- ity for 18F-FDG PET and/or 18F-FDG were determined to have chronic pain, sity of Turku and the University of PET/CT detection of posttransplant with no revision surgery scheduled. The Eastern Finland (Kuopio; all in Fin- lymphoproliferative disorder were 89.7%

Newsline 19N and 90.9%, respectively. Pooled positive findings took into consideration the 68Ga-PSMA vs 11C-Choline and negative likelihood ratios and the lesion detection rate of the 68Ga-PSMA PET/CT in Salvage Lymph diagnostic odds ratio were 8.9, 0.13, strategy and the cost of follow-up in con- Node Dissection and 70.4, respectively. The authors con- ventional care. The authors concluded that In an article e-published on Feb- 18 cluded that ‘‘ F-FDG PET or PET/CT ‘‘In this exploratory economic evalua- ruary 18 ahead of print in the Journal 68 NEWSLINE demonstrated good diagnostic perfor- tion, using Ga-PSMA PET/MRI to de- of Urology, Fossati et al. from re- mance for the detection of posttrans- tect prostate cancer recurrence appears to search sites in Italy, the United States, plant lymphoproliferative disorder, but be cost-effective relative to usual care.’’ Germany, Belgium, and Austria reported Clinical and Experimental large prospective studies are needed to on a large study comparing 11C-choline Metastasis strengthen these findings.’’ and 68Ga-prostate-specific membrane Diagnostics (Basel) Advanced Imaging antigen (68Ga-PSMA) PET/CT in Cost-Effectiveness of Advantages in Nonlocalizing men undergoing salvage lymph node 68Ga-PSMA PET/MR in Primary Hyperparathyroidism dissection for nodal recurrent prostate cancer. The study included 641 men in Biochemical Recurrence of Frank et al. from Loma Linda Uni- whom prostate-specific antigen (PSA) Prostate Cancer versity Medical Center/Loma Linda levels were rising with nodal recur- In an article e-published on Feb- University School of Medicine (CA) rence after radical prostatectomy. All ruary 17 ahead of print in Clinical and reported on February 17 ahead of print underwent salvage lymph node dis- Experimental Metastasis, Gordon et in Laryngoscope on a study intended al. from the QIMR Berghofer Medical to determine whether different types section. A total of 407 patients un- derwent 11C-choline PET/CT imaging Research Institute, the University of of advanced imaging are more cost- 68 Queensland, Queensland University of effective than primary bilateral neck and 234 underwent Ga-PSMA imag- Technology (all in Brisbane, Australia), exploration in the management of non- ing. The focus was on underestimation and Princess Alexandra Hospital (Wool- localizing primary hyperparathyroidism. of tumor burden, defined as the differ- loongabba, Australia) reported on a The study used a decision tree model ence between the number of positive study exploring the cost-effectiveness and financial data from Medicare pa- nodes on final pathology and number of 68Ga-prostate-specific membrane tients. A total of 347 patients were of positive sites on PET/CT with each antigen (68Ga-PSMA) PET/MR imaging included and were scheduled to have of the tracers. The authors found that for staging in men with biochemical a parathyroidectomy for primary hy- the extent of underestimation of tumor recurrence of prostate cancer. The perparathyroidism with either positive, burden was significantly higher with 11 methodology used a decision-analytic concordant ultrasound and sestamibi C-choline. Including PSA in the anal- model with Markov chains, in which imaging or negative sestamibi and neg- ysis, the underestimation of tumor 68 68Ga-PSMA PET/MR imaging was com- ative ultrasound. Modeling indicated burden was lower with Ga-PSMA # pared with conventional clinical ap- the following costs and success rates when the PSA was 1.5 ng/mL and proaches in staging patients with for each of the following: bilateral the underestimation of the 2 tracers . suspected prostate cancer recurrence. neck exploration, $9,578 and 97.3%; was similar when PSA was 1.5 ng/ Men with biochemical recurrence SPECT 1 minimally invasive para- mL. In addition, the higher the number from a study in Brisbane (n 5 30) pro- thyroidectomy, $8,197, 98.6%; SPECT/ of positive spots, the higher the under- vided key estimates for the model. The CT 1 minimally invasive parathyroid- estimation of tumor burden with either authors found that, on average, integra- ectomy, $8,271 and 98.9%; and 4D-CT 1 tracer. The authors concluded that tion of 68Ga-PSMA into the care strat- minimally invasive parathyroidectomy, PET/CT scanning ‘‘significantly under- egy was expected to cost US$39,426 $8,146, 99%. The authors summarized estimates the burden of prostate cancer and produce 7.48 life years, whereas their findings by saying that ‘‘in patients recurrence, regardless of the tracer used. the usual clinical approach was ex- with nonlocalizing primary hyperpara- Although 68Ga-PSMA was associated pected to cost US$44,667 and yield thyroidism, advanced imaging is associ- with a lower rate of underestimation 7.41 life years. 68Ga-PSMA was poten- ated with cost-savings compared to routine in patients with a PSA ,1.5 ng/mL and tially cost saving (US$5,258) and bilateral neck exploration.’’ The greater limited nodal tumor load, for ‘‘all other somewhat more effective (by 0.07 life the accuracy of the imaging approach, men, there was no benefit from 68Ga- years). The likelihood that the 68Ga- the higher the predicted cost savings PSMA over 11C-choline in assessing PSMA strategy was cost-effective at ac- and the lower the imaging costs. the extent of nodal recurrence.’’ ceptable thresholds was 87%. These Laryngoscope Journal of Urology

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