NUCLEAR MEDICINE: LOOKING AHEAD TO 2020
Eric M. Rohren, M.D. Ph.D. Professor and Chair, Department of Radiology Baylor College of Medicine Houston, Texas Objectives
. What is molecular imaging? . How do we think about molecular imaging? . What are the features of success? … and failure? Molecular Imaging Agents
2-[18F ]-2-Deoxy-D-Glucose • Analog of glucose • Uptake mirrors glucose utilization
HO O OH
HO OH 18F FDG-PET/CT: What are We Imaging Exactly?
. Imaging regional localization of FDG FDG uptake and concentration at a cellular level Glucose transporter receptor expression Hexokinase expression Low phosphatase activity Cellular density
Tracer delivery (perfusion/concentration) “METABOLISM”
Scanner limitations (size, motion, etc.)
A Tale of Two … Gastric Cancers
. Patient 1 66 year old woman with upper abdominal pain and weight loss . Patient 2 58 year old man with weight loss and early satiety Patient 1 Patient 2 Molecular Imaging
Gene expression
Receptor Imaging Cellular Proliferation and Hypoxia
Protein and Membrane Catabolism
Glucose “Metabolism”
Instrumentation PET SPECT MR NIR/Optical U.S. Approved Radiopharmaceuticals Clinical Use . 18F-FDG . 18F-fluoride . 82Rb-chloride . 13N-Ammonia U.S. Approved Radiopharmaceuticals Recent . 123I-ioflupane . 99mTc-tilmanocept . 11C-choline . 18F-amyloid (florbetapir, florbetaben, flutametamol) 223 . RaCl2 U.S. Approved Radiopharmaceuticals In Development . 123I-ioflupane . 99mTc-tilmanocept . 11C-choline . 18F-amyloid (florbetapir, florbetaben, flutametamol) 223 . RaCl2 . 68Ga-DOTA-TOC/NOC/TATE . 177Lu-DOTATATE . 18F-PSMA . 18F-flurpiridaz . 131I-ultratrace iobenguane (MIBG) Theranostic Approach
Cancer Cell Radionuclides for Therapy
Radionuclide Emission Energy (MeV) Range (mm) Half-Life
Indium-111 Auger / g 0.61 0.5 2.8 days Yttrium-90 Beta 2.27 11 2.7 days
Lutetium-177 B / g 0.49 2 6.7 days Bismuth-213 a 8.32 0.04 - 0.1 46 min Considerations . Performance . Time/Speed . Radiation dose . Availability/Access . Cost Case Studies Imaging Lymphoma 67Gallium Citrate
. Introduced to clinical practice 1969 . Physical characteristics T½ 78 hours Photopeaks 93 keV, 185 keV, 300 keV, 394 keV . Bound to transferrin and lactoferrin in plasma . Receptor-mediated uptake in tumor cells . Used for imaging a variety of malignancies 67Ga-SPECT and Lymphoma
. Uptake of gallium is dependent on tumor grade . Hodgkin lymphoma: 80-90% sensitivity . Non-Hodgkin lymphoma: 60-90% sensitivity
. Imaging Protocol Injection of 370 MBq (10 mCi) Planar imaging at 48 hrs, sometimes longer SPECT 18F-Fluorodeoxyglucose
HO O OH
HO OH 18F . 2-deoxy-2-[18F]fluoro-D-glucose . Physical characteristics T½ 110 minutes Photopeak 511 keV . Cellular uptake via glucose receptors Retrospective Review: Duke Univsersity 1999
. 47 patients evaluated with both 67Ga-SPECT and FDG-PET . 7 day mean interval between studies (0-59d) . No interval treatment . Studies read with available clinical and radiological correlation Conclusions
. FDG-PET is more accurate than 67Ga- SPECT in staging patients with Hodgkin and Non-Hodgkin lymphoma 42 of 47 patients correctly staged by PET 34 of 47 patients correctly staged by gallium 8 of 10 discrepant cases resolved in favor of PET 67Ga (10 mci) 18F-FDG (20 mCi) Radiation dose ~25 mSv ~15 mSv Total Time 2-4 days 3 hours Scan Time 60-90 minutes 60-90 minutes Cost $$ $$$ Accuracy ++ ++++ Quantification No Yes Radiopharmaceuticals for Treatment of Bone Metastases – Radium-223
223 RaCl2 - Half life 11.43 days - Multistep decay a (95%, 4 per decay event) - Low abundance b, g Decay Cascade of 223Ra
223Ra 11.4 d 211Po 0.5 s a 219Rn a 4.0 s b 207Pb stable a 211Bi 2.2 m 215Po b 1.8 ms b a 207Tl a 4.8 m 211 a-emitter (94% of emitted energy) Pb 36.1 m Total Energy / decay: Approx. 28 MeV
(From Oyvind Bruland MD, PhD)
Bone Imaging 18F-Fluoride
18F 18F 18F 18F
18F
. Sodium [18F]fluoride . Physical characteristics T½ 110 minutes Photopeak 511 keV 18F- exchange for OH- in hydroxyapatite 18F- migration into crystalline matrix of bone 90% serum clearance at 1 hr
Imaging Comparison
. Study: 72 patients with advanced breast cancer at high risk for skeletal disease 99mTc SS NaF PET/CT Sensitivity 81% 100% Specificity 63% 75% PPV 81% 89% NPV 63% 100% Accuracy 75% 92%
. Change in patient management in 12 patients (17%) based on NaF-PET/CT
Damle N, et. al. 2007. J Nucl Med 48:142P. TFI10 VF10 TFI10 VF10 Baseline 2729 193 cc Baseline 5576 329 cc Post-Therapy 8389 522 cc Post-Therapy 898 76 cc % Change +207.4% +170.4% % Change -83.9% -76.9% J Nucl Med 2015; 56:1177-1184 99mTc-MDP 18F-FDG PET/CT (20 mci) (5 mCi) Radiation dose ~3-5 mSv ~20 mSv Total Time 3-4 hours 2 hours Scan Time 45 minutes 20 minutes Cost $ $$$ Accuracy ++ ++++ Quantification No Yes CMS Decision Memo
. Based on the result of data analysis . NOPR – Scanning under CED 2839 scans / 2217 patients Change in management in 40.3% of patients
Concluded that NaF-PET/CT is NOT reasonable and necessary NO COVERAGE CMS Questions
. Does the addition of NaF-PET/CT imaging lead to: A change in patient management to more appropriate palliative care; or A change in patient management to more appropriate curative care; or Improved quality of life; or Improved survival? A Lingering issue: REIMBURSEMENT FLORBETAPIR PET SCAN FDA Decision
. Approved for clinical use 4/10/2012 Safe Effective CMS Decision Memo
“… the evidence is insufficient to conclude that the use of positron emission tomography (PET) amyloid-beta (Aβ) imaging is reasonable and necessary for the diagnosis or treatment of [patients] … with dementia or neurodegenerative disease, and thus PET Aβ imaging is not covered …” CMS Decision Memo
. Do the results of PET Aβ imaging lead to improved health outcomes?
Effective Treatment The Near Future
. Imaging with PET will replace some general nuclear medicine applications NETTER-1 Trial