JANUARY 2021 THE CLINICAL TRIALS NETWORK NEWSLETTER Pathways Table of Contents Molecular Imaging 2020: Year in Review 1 Molecular Imaging John Sunderland, PhD, MBA; University of Iowa and 2020: Year in Jonathan McConathy, MD; University of Alabama Review Co-Chairs, Clinical Trials Network 4 FAP Agents he year 2020 may long linger in our minds for a number of reasons, but some of those John Sunderland, PhD, MBA Jonathan E. McConathy, MD, PhD thoughts should be positive. The field Director, Small Animal Imaging Director, Advanced Imaging Facility T Core and PET Imaging Center, and Director, Division of Molecular 6 Therapy Toolkit of molecular imaging and nuclear medicine Department of Radiology, Imaging and Therapeutics, accomplished a phenomenal milestone: the University of Iowa University of Alabama-Birmingham U.S. Food and Drug Administration (FDA) 7 CTN Education approved three new molecules (FES, tau and Cerianna™ (fluoroestradiol F-18) Committee Welcomes PSMA), one new isotope (copper-64) and one On May 20, 2020, the FDA approved the New Co-Chair new production method (cyclotron-generated positron emission tomography (PET) imaging gallium-68). agent F-18 fluoroestradiol (Cerianna™, Zionexa Updated CTN The development of new drugs and therapeutic USA) as the first F-18-labeled PET agent for Courses – Be on the biological products used to advance medicine detecting estrogen receptor (ER)–positive lesions Lookout in 2021! and improve healthcare requires innovation, as an adjunct to biopsy in patients with recurrent determination, team effort and, of course, or metastatic breast cancer. This new agent 8 My Path to Molecular money. But key to all of this is understanding the will enhance therapeutic decision–making by Imaging Research science about the diseases and conditions that providing total body information of the estrogen new products are designed to treat, performing receptor status of tumors.1 “This approval is based FDA Approves Cyclo- methodical testing to achieve reproducible on multiple single institution studies in the US and tron-Produced Ga-68 and consistent results, establishing irrefutable Europe, which are in the process of confirmation DOTATOC and quality control in manufacturing procedures and in multi-center trials now including EAI 142. Ga-68 PSMA-11 obtaining appropriate regulatory advice before These trials show that FES predicts clinical new radiopharmaceuticals and therapies are benefit with endocrine therapy,” said Hannah approved for use in humans. The availability Linden, MD, Athena Distinguished Professorship 9 Save-the-Dates of these new drugs, biological products of Breast Cancer Research at the University of and manufacturing procedures often means Washington. “Like genomic profiling in earlier CTN Phantom desperately needed new treatment options can stage tumors, FES has the potential to reduce Analysis Tool be made available to our patients—and what the use of cytotoxic agents in metastatic breast can be more positive than that? cancer by identification of which patients could 2020 was indeed a year of “firsts” for PET benefit from ER-directed therapy. The emerging tracers. Herein we provide a short review of field of molecularly targeted synergistic agents these events in order of approval date. makes this even more feasible.” Continued on page 2. See Molecular Imaging 2020: Year in Review Molecular Imaging 2020: Year in Review. Continued from page 1. Cerianna is not indicated for imaging other receptors, such Detectnet™ (copper Cu 64 dotatate) process to manufacture the final drug product. Cyclotron-produced the field of nuclear medicine and molecular imaging with the as human epidermal growth factor receptor 2 (HER2) and the On September 8, 2020, RadioMedix Inc. and its commercial Ga-68 DOTATOC consistently results in production of 40–50 approval of three new molecules, one new isotope and one new progesterone receptor (PR). The ER status of a patient’s tumor partner Curium announced FDA approval of Detectnet™ mCi of Ga-68 DOTATOC rather than the 10–25 mCi typically production method. In fact, the past ten years have been an and recurrence of breast cancer should be confirmed with tissue (copper-64 DOTATATE injection). Detectnet is the first Cu-64- produced by a Ge-68/Ga-68 generator. The new process amazing era of growth for the field. Please review the timeline biopsy. When interpreting images, it is important to remember labeled PET agent indicated for the localization of somatostatin allows for multi-dose vials and provides a viable alternative to on pages 2 and 3 of this issue to follow the approvals of single that the uptake of F-18 fluoroestradiol depends on the ER receptor positive neuroendocrine tumors (NETs) in adult patients. Ge-68/Ga-68 generators for facilities with cyclotrons. The FDA photon tracers, PET oncology tracers, PET brain tracers, and density and function in tumors and physiologic tissue, including The 12.7-hour half-life of Cu-64 allows for the increased also approved cyclotron production of Ga-68 PSMA-11 at the radiopharmaceutical therapies that occurred over the past in the liver, ovary, and uterus. Tumors identified as ER-positive availability across the U.S. through shipments from centralized University of California, San Francisco (UCSF).7 decade. It’s an amazing chronicle of innovation and progress. on PET/CT should be based on comparison with normal tissue production sites.5 References background of organs without high physiologic uptake.2 As noted in the package insert, there may be a risk for image Gallium 68 PSMA-11 (Ga 68 PSMA-11) 1. Estrogen Receptor Agent Approved. JNM Newsline. J Nucl Med. July misinterpretation with Detectnet. Caution should be used, as On December 1, 2020, the FDA approved gallium-68 PSMA- 2020, 61(7):20N. Tauvid™ (F-18 flortaucipir) a variety of other tumors also express somatostatin receptors. 11, the first PET imaging agent for prostate-specific membrane 2. CERIANNA™ (fluoroestradiol F 18) Injection, for intravenous use. The FDA granted approval of Tauvid™ for intravenous Increased uptake might also be seen in other non-cancerous antigen (PSMA)–positive lesions in men with prostate cancer. Prescribing Information. FDA Reference ID: 4610145. injection to Avid Radiopharmaceuticals Inc. on May 28, pathologic conditions, in subacute inflammation, or as a normal The approval was granted to the University of California, Los 3. FDA Approves First Drug to Image Tau Pathology in Patients Being Evaluated for Alzheimer’s Disease. FDA NEWS RELEASE May 28, 2020. 2020. It is the first tau diagnostic PET imaging agent used physiologic variant (e.g., uncinate process of the pancreas). Angeles (UCLA) and UCSF following two prospective clinical www.fda.gov/news. to assess adult patients with cognitive impairment who are Additionally, a negative Detectnet scan in patients who do not trials involving a total of 960 prostate cancer patients. This 4. Mattay, VS, et al. Brain Tau Imaging: Food and Drug Administration being evaluated for Alzheimer’s disease (AD). Tau is one of have a history of NET disease does not rule out disease.6 approval process involved a great collaboration between the Approval of 18F-Flortaucipir Injection. J Nucl Med 2020. 61(10):1411-12. Published online Aug. 4, 2020. doi: 10.2967/jnumed.120.252254. two proteins, along with amyloid, recognized as a hallmark SNMMI Clinical Trials Network, two academic institutions, 5. RadioMedix and Curium Announce FDA Approval of Detectnet (copper Cu of Alzheimer’s disease. When diseased tau proteins develop Cyclotron-Produced Gallium-68 and the FDA that will hopefully serve as a model for future 64 dotatate injection) in the U.S. Press Release September 8, 2020. inside neurons in the brain, neurofibrillary tangles (NFTs) are On October 14, 2020, the University of Iowa received collaborations and radiopharmaceutical approvals.8 www.curiumpharma.com/. formed. Tauvid is indicated for brain imaging to estimate the approval for cyclotron-produced gallium-68 (Ga-68) via a Ga-68 PSMA-11 is indicated for patients with suspected 6. Detectnet (copper Cu 64 dotatate injection) for intravenous use. Prescribing density and distribution of these aggregated tau NFTs. It helps supplement to their DOTATOC NDA, which was approved prostate cancer metastasis who are potentially curable by information. FDA Reference ID: 4666138. 7. SNMMI Press Release. FDA Approves Cyclotron-Produced Ga-68 identify the presence of tau pathology by binding to sites in the in 2019 for the localization of NETs in adults and children. surgery or radiation therapy and for patients with suspected DOTATOC for Neuroendocrine Tumors. October 20, 2020. brain associated with tau protein misfolding.3 Cyclotron-produced Ga-68 will allow for higher-volume recurrence based on elevated PSA levels. Once administered www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=34801. It is important to remember that Tauvid is not indicated for production. The newly approved process uses a liquid target by intravenous injection, Ga-68 PSMA-11 binds to PSMA, 8. SNMMI Press Release December 2, 2020. FDA Announces First-Ever evaluating patients with chronic traumatic encephalopathy. filled with a zinc-68 solution to produce Ga-68 in the cyclotron. allowing for the presence of PSMA-positive prostate cancer Approval of PSMA PET for Prostate Cancer Imaging. www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=35254. 9 Furthermore, a tau-positive scan alone does not establish a The target solution is transferred to a cassette-based synthesis lesions to be imaged by PET. 9. FDA NEWS RELEASE. FDA Approves First PSMA-Targeted PET Imaging diagnosis of AD or other cognitive disorders.4 module that purifies the gallium-68 and performs the chemistry The year 2020 certainly left some positive memories in Drug for Men with Prostate Cancer. December 1, 2020. 2 3 Figure 1. Maximum intensity projections (MIP) of PET/CT scans in patients suffering from metastasized pancreatic cancer (A) and breast cancer (C). (B) Maximum tissue uptake of 68Ga-FAPI-02 10 min, 1 h and 3 h after intravenous administration to a patient with Special Feature metastasized breast cancer.