Sanjay Thamake

Validation of Several SUV-Based Parameters Derived from 18F-FDG PET for Prediction of Survival After SIRT of Hepatic Metastases from Colorectal Cancer

90Y radioembolization (selective internal radiation therapy [SIRT]) is a valuable therapeutic option for unresectable hepatic metastases arising from primary colorectal cancer. The present study evaluated the prognostic value of 18F-FDG PET/CT metabolic parameters for predicting survival after SIRT. Methods: Eighty patients with hepatic metastases of colorectal cancer were treated with SIRT. 18F-FDG PET/CT was performed at baseline and 3 mo after the treatment. Metabolic volume, total lesion glycolysis, and maximum and peak standardized uptake value (SUVmax and SUVpeak, respectively) according to PET Response Criteria in Solid Tumors (PERCIST 1.0) were obtained from 3 liver lesions in each patient, and the corresponding percentage changes from baseline to follow-up were calculated. Tumor response was defined as more than a 30% decrease in these parameters. Furthermore, response was evaluated in accordance with Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Toxicity events and survival were recorded. Results: Overall median survival after SIRT was 60 wk. Responders who had a change in metabolic volume or total lesion glycolysis had significantly longer survival (92 vs. 49 wk [P = 0.006] and 91 vs. 48 wk [P = 0.025], respectively). However, neither RECIST 1.1 criteria nor changes in SUVpeak or SUVmax after treatment predicted outcome (P = 0.086 for RECIST; P = 0.310 for change in SUVpeak; P = 0.155 for change in SUVmax). Conclusion: Changes in metabolic volume and total lesion glycolytic rate as measured by 18F-FDG PET predicted survival in patients with hepatic metastases from colorectal cancer, whereas changes in SUVpeak or SUVmax and RECIST 1.1 criteria did not predict survival.

Radiosynthesis of clinical doses of 68Ga-DOTATATE (GalioMedix™) and validation of organic-matrix-based 68Ge/68Ga generators

INTRODUCTION 68Ga-DOTATATE is a radiolabeled peptide-based agonist that targets somatostatin receptors overexpressed in neuroendocrine tumors. Here, we present our results on validation of organic matrix 68Ge/68Ga generators (ITG GmbH) applied for radiosynthesis of the clinical doses of 68Ga-DOTATATE (GalioMedixTM). METHODS The clinical grade of DOTATATE (25 μg±5 μg) compounded in 1 M NaOAc at pH=5.5 was labeled manually with 514±218 MBq (13.89±5.9 mCi) of 68Ga eluate in 0.05 N HCl at 95°C for 10 min. The radiochemical purity of the final dose was validated using radio-TLC. The quality control of clinical doses included tests of their osmolarity, endotoxin level, radionuclide identity, filter integrity, pH, sterility and 68Ge breakthrough. RESULTS The final dose of 272±126 MBq (7.35±3.4 mCi) of 68Ga-DOTATATE was produced with a radiochemical yield (RCY) of 99%±1%. The total time required for completion of radiolabeling and quality control averaged approximately 35 min. This resulted in delivery of 50%±7% of 68Ga-DOTATATE at the time of calibration (not decay corrected). CONCLUSIONS 68Ga eluted from the generator was directly applied for labeling of DOTA-peptide with no additional pre-concentration or pre-purification of isotope. The low acidity of 68Ga eluate allows for facile synthesis of clinical doses with radiochemical and radionuclide purity higher than 98% and average activity of 272±126 MBq (7.3±3 mCi). There is no need for post-labeling C18 Sep-Pak purification of final doses of radiotracer. Advances in knowledge and implications for patient care. The clinical interest in validation of 68Galabeled agents has increased in the past years due to availability of generators from different vendors (Eckert-Ziegler, ITG, iThemba), favorable approach of U.S. FDA agency to initiate clinical trials, and collaboration of U.S. centers with leading EU clinical sites. The list of 68Ga-labeled tracers evaluated in clinical studies should growth because of the sensitivity of PET technique, the simplicity of the shakebake approach for the dose preparation and reliability of 68Ge/68Ga generators. Our studies have confirmed the reproducible elution profile, and high reliability of ITG GmbH generators required for routine doses preparation according to FDA recommendations.