Qualification of PET scanners for use in multicenter cancer clinical trials: the American College of Radiology Imaging Network experience.

UNLABELLED: The PET Core Laboratory of the American College of Radiology Imaging Network (ACRIN) qualifies sites to participate in multicenter research trials by quantitatively reviewing submitted PET scans of uniform cylinders to verify the accuracy of scanner standardized uptake value (SUV) calibration and qualitatively reviewing clinical PET images from each site. To date, cylinder and patient data from 169 PET scanners have been reviewed, and 146 have been qualified. METHODS: Each site is required to submit data from 1 uniform cylinder and 2 patient test cases. Submitted phantom data are analyzed by drawing a circular region of interest that encompasses approximately 90% of the diameter of the interior of the phantom and then recording the mean SUV and SD of each transverse slice. In addition, average SUVs are measured in the liver of submitted patient scans. These data illustrate variations of SUVs across PET scanners and across institutions, and comparison of results with values submitted by the site indicate the level of experience of PET camera operators in calculating SUVs. RESULTS: Of 101 scanner applications for which detailed records of the qualification process were available, 12 (12%) failed because of incorrect SUV or normalization calibrations. For sites to pass, the average cylinder SUV is required to be 1.0 +/- 0.1. The average SUVs for uniform cylinder images for the most common scanners evaluated-Siemens Biograph PET/CT (n = 43), GE Discovery LS PET/CT (n = 15), GE Discovery ST PET/CT (n = 34), Philips Allegro PET (n = 5), and Philips Gemini PET/CT (n = 11)-were 0.99, 1.01, 1.00, 0.98, and 0.95, respectively, and the average liver SUVs for submitted test cases were 2.34, 2.13, 2.27, 1.73, and 1.92, respectively. CONCLUSION: Minimizing errors in SUV measurement is critical to achieving accurate quantification in clinical trials. The experience of the ACRIN PET Core Laboratory shows that many sites are unable to maintain accurate SUV calibrations without additional training or supervision. This raises concerns about using SUVs to quantify patient data without verification.

Comparison of diffuse optical tomography of human breast with whole-body and breast-only positron emission tomography.

We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations were found between total hemoglobin concentration and tissue scattering measured by DOT, and fluorodeoxyglucose (18F-FDG) uptake. In light of these observations, we suggest potential benefits of combining both PET and DOT for characterization of breast lesions.

Accuracy of [18F]fluorodopa positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism.

OBJECTIVES: Focal lesions in infants with congenital hyperinsulinism (HI) represent areas of adenomatosis that express a paternally derived ATP-sensitive potassium channel mutation due to embryonic loss of heterozygosity for the maternal 11p region. This study evaluated the accuracy of 18F-fluoro-l-dihydroxyphenylalanine ([18F]DOPA) positron emission tomography (PET) scans in diagnosing focal vs. diffuse disease and identifying the location of focal lesions. DESIGN: A total of 50 infants with HI unresponsive to medical therapy were studied. Patients were injected iv with [18F]DOPA, and PET scans were obtained for 50-60 min. Images were coregistered with abdominal computed tomography scans. PET scan interpretations were compared with histological diagnoses. RESULTS: The diagnosis of focal or diffuse HI was correct in 44 of the 50 cases (88%). [18F]DOPA PET identified focal areas of high uptake of radiopharmaceutical in 18 of 24 patients with focal disease. The locations of these lesions matched the areas of increased [18F]DOPA uptake on the PET scans in all of the cases. PET scan correctly located five lesions that could not be visualized at surgery. The positive predictive value of [18F]DOPA in diagnosing focal adenomatosis was 100%, and the negative predictive value was 81%. CONCLUSIONS: [18F]DOPA PET scans correctly diagnosed 75% of focal cases and were 100% accurate in identifying the location of the lesion. These results suggest that [18F]DOPA PET imaging provides a useful guide to surgical resection of focal adenomatosis and should be considered as a guide to surgery in all infants with congenital HI who have medically uncontrollable disease.

Diagnosis and localization of focal congenital hyperinsulinism by 18F-fluorodopa PET scan.

OBJECTIVES: To assess the accuracy of 18F-fluoro-L-dihydroxyphenylalanine ([18F]-DOPA) PET scans to diagnose focal versus diffuse disease and to localize focal lesions in infants with congenital hyperinsulinism. STUDY DESIGN: Twenty-four infants with hyperinsulinism unresponsive to medical therapy were studied. Patients were injected intravenously with [18F]-DOPA, and PET scans were obtained for 1 hour. Images were coregistered with abdominal CT scans. RESULTS: The diagnosis of focal or diffuse hyperinsulinism was correct in 23 of the 24 cases (96%) and equivocal in 1 case. [18F]-DOPA PET identified focal areas of high uptake of radiopharmaceutical in 11 patients. Pathology results confirmed that all 11 had focal adenomatosis, and the locations of these lesions matched the areas of increased [18F]-DOPA uptake on the PET scans in all of the cases. CONCLUSIONS: [18F]-DOPA PET scans were 96% accurate in diagnosing focal or diffuse disease and 100% accurate in localizing the focal lesion. These results suggest that [18F]-DOPA PET imaging should be considered in all infants with congenital hyperinsulinism who need to have pancreatectomy.

N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

UNLABELLED: There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. METHODS: This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. RESULTS: In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in rat brain (>96% of radioactivity was recovered as parent compound at 1 h after injection). However, it metabolized rapidly in the blood. Less than 7% of the radioactivity recovered from plasma was the parent compound, with the majority of radioactivity in the plasma not extractable by ethyl acetate. Blocking studies showed significant decreases in the uptake of 4-(18)F-ADAM in the brain regions (hypothalamus, hippocampus, and striatum) where SERT concentrations are high when rats were pretreated with (+)McN5652 (2 mg/kg 5 min before intravenous injection of 4-(18)F-ADAM). However, changes in the uptake of 4-(18)F-ADAM in these brain regions were less significant when rats were pretreated with either methylphenidate or nisoxetine. The baboon study showed that uptake of 4-(18)F-ADAM in the midbrain peaked at approximately 1 h after injection and then declined slowly. The ratios of the radioactivity in the midbrain to that in the cerebellum (where the concentration of SERT is low) at 2 and 3 h after injection were 3.2 and 4.2, respectively. CONCLUSION: 4-(18)F-ADAM is suitable as a PET radioligand for studying SERT in the living brain. Further characterization of this new radioligand in humans is warranted.