First-in-human trial of 64Cu-SARTATE PET imaging of patients with neuroendocrine tumours demonstrates high tumor uptake and retention, potentially allowing prospective dosimetry for peptide receptor radionuclide therapy

Hicks RJ1Jackson P2Kong G2Ware RE2Hofman MS2Pattison DA3Akhurst T2Drummond E2Roselt P2Callahan J2Price R4Jeffery C5Hong E2Noonan W6Herschtal A2Hicks LJ7Harris M8Hedt A5Paterson BM9Donnelly P10.

J Nucl Med. 2018 Nov 15 (epub ahead of print)

Abstract

Imaging of somatostatin receptor (SSTR) expression is an established technique for staging of neuroendocrine neoplasia (NEN) and determining the suitability of patients for peptide receptor radionuclide therapy (PRRT). PET/ CT utilizing 68Ga-labeled somatostatin analogues (SSAs) is superior to earlier agents, but the rapid physical decay of the radionuclide poses logistic and regulatory challenges. 64Cu has attractive physical characteristics for imaging and provides a diagnostic partner for the therapeutic radionuclide 67Cu. Based on promising pre-clinical studies, we have performed a first-time-in-human trial of 64Cu-MeCOSar-octreotate (64Cu-SARTATE) to assess its safety and ability to localise disease at early and late imaging time-points. Methods: In a prospective trial, 10 patients with known NEN and positive 68Ga-DOTA-octreotate (GaTate) PET/CT underwent serial PET/CT imaging at 30 min, 1, 4 and 24 hours following injection of 64Cu-SARTATE. Adverse reactions were recorded and laboratory testing was performed during infusion and at 1 and 7 days post-imaging. Images were analysed for lesion and normal organ uptake and clearance to assess lesion contrast and perform dosimetry estimates. Results: 64Cu-SARTATE was well tolerated during infusion and throughout the study, with three patients experiencing mild infusion-related events. High lesion uptake and retention were observed at all imaging time-points. There was progressive hepatic clearance over time, providing highest lesion to liver contrast at 24 hours. Image quality remained high at this time. Comparison of 64Cu-SARTATE PET/CT obtained at 4 hours to GaTate PET/CT obtained at 1 hour indicated comparable or superior lesion detection in all patients, especially in the liver. As expected, highest early physiologic organ uptake was observed in the kidneys, liver and spleen. Conclusion: 64Cu-SARTATE is safe and has excellent imaging characteristics. High late-retention in tumour and clearance from the liver suggests suitability for diagnostic studies as well as for prospective dosimetry for 67Cu-SARTATE PRRT, while the half-life of 64Cu would also facilitate GMP production and distribution to sites without access to 68Ga.

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