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A generator-produced gallium-68 radiopharmaceutical for PET imaging of myocardial perfusion.

ABSTRACT: Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing 99Mo/99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality 68Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged. Herein, we report a novel 68Ga-complex identified through mechanism-based cell screening that holds promise as a generator-produced radiopharmaceutical for PET MPI.

SUBMITTER: Sharma V

PROVIDER: S-EPMC4212944 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A generator-produced gallium-68 radiopharmaceutical for PET imaging of myocardial perfusion.

Sharma Vijay V Sivapackiam Jothilingam J Harpstrite Scott E SE Prior Julie L JL Gu Hannah H Rath Nigam P NP Piwnica-Worms David D

PloS one 20141029 10

Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing 99Mo/99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality 68Ga, an isotope with excellent emission characteristics for clinical PET imaging, ...[more]

PMID: 25353349

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Project description:BackgroundProstate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [68Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.MethodsEligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[18F]FDG PET and/or 131I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [68Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[18F]FDG PET CT/MRI for lesion location and relative intensity.ResultsTwelve patients underwent [68Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[18F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[18F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.Conclusions[68Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[18F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.

Project description:IntroductionStrontium-82/Rubidium-82 (82Sr/82Rb) generators are used widely for positron emission tomography (PET) imaging of myocardial perfusion. In this study, the 82Rb isotope yield and production efficiency of two FDA-approved 82Sr/82Rb generators were compared.MethodsN = 515 sequential daily quality assurance (QA) reports from 9 CardioGen-82® and 9 RUBY-FILL® generators were reviewed over a period of 2 years. A series of test elutions was performed at different flow-rates on the RUBY-FILL® system to determine an empirical correction-factor used to convert CardioGen-82® daily QA values of 82Rb activity (dose-calibrator 'maximum' of 50 mL elution at 50 mL·min-1) to RUBY-FILL® equivalent values (integrated 'total' of 35 mL elution at 20 mL·min-1). The generator yield (82Rb) and production efficiency (82Rb yield/82Sr parent activity) were measured and compared after this conversion to a common scale.ResultsAt the start of clinical use, the system reported 82Rb activity from daily QA was lower for CardioGen-82® vs RUBY-FILL® (2.3 ± 0.2 vs 3.0 ± 0.2 GBq, P < 0.001) despite having similar 82Sr activity. Dose-calibrator 'maximum' (CardioGen-82®) values were found to under-estimate the integrated 'total' (RUBY-FILL®) activity by ~ 24% at 50 mL·min-1. When these data were used to convert the CardioGen-82 values to a common measurement scale (integrated total activity) the CardioGen-82® efficiency remained slightly lower than the RUBY-FILL® system on average (88 ± 4% vs 95 ± 4%, P < 0.001). The efficiency of 82Rb production improved for both systems over the respective periods of clinical use.Conclusions82Rb generator yield was significantly under-estimated using the CardioGen-82® vs RUBY-FILL® daily QA procedure. When generator yield was expressed as the integrated total activity for both systems, the estimated 82Rb production efficiency of the CardioGen-82® system was ~ 7% lower than RUBY-FILL® over the full period of clinical use.

Dataset Information

A generator-produced gallium-68 radiopharmaceutical for PET imaging of myocardial perfusion.

Publications

A generator-produced gallium-68 radiopharmaceutical for PET imaging of myocardial perfusion.

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