64Cu-sartaTE PET imaging of patients with neuroendocrine tumors demonstrates high tumor uptake and retention, potentially allowing prospective dosimetry for peptide receptor radionuclide therapy

Rodney J. Hicks, Price Jackson, Grace Kong, Robert E. Ware, Michael S. Hofman, David A. Pattison, Timothy A. Akhurst, Elizabeth Drummond, Peter Roselt, Jason Callahan, Roger Price, Charmaine M. Jeffery, Emily Hong, Wayne Noonan, Alan Herschtal, Lauren J. Hicks, Amos Hedt, Matthew Harris, Brett M. Paterson, Paul S. Donnelly

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16 Citations (Scopus)

Abstract

Imaging of somatostatin receptor expression is an established technique for staging of neuroendocrine neoplasia and determining the suitability of patients for peptide receptor radionuclide therapy. PET/CT using 68Ga-labeled somatostatin analogs 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 preclinical studies, we have performed a first-time-in-humans trial of 64Cu-MeCOSar-Tyr3-octreotate (64Cu-SARTATE) to assess its safety and ability to localize disease at early and late imaging time-points. Methods: In a prospective trial, 10 patients with known neuroendocrine neoplasia and positive for uptake on 68Ga-DOTA-octreotate (68Ga-DOTATATE) PET/CT underwent serial PET/CT imaging at 30 min, 1 h, 4 h, and 24 h after injection of 64Cu-SARTATE. Adverse reactions were recorded, and laboratory testing was performed during infusion and at 1 and 7 d after imaging. Images were analyzed 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 3 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 the highest lesion-to-liver contrast at 24 h. Image quality remained high at this time. Comparison of 64Cu-SARTATE PET/CT obtained at 4 h to 68Ga-DOTATATE PET/CT obtained at 1 h indicated comparable or superior lesion detection in all patients, especially in the liver. As expected, the highest early physiologic organ uptake was in the kidneys, liver, and spleen. Conclusion: 64Cu-SARTATE is safe and has excellent imaging characteristics. High late-retention in tumor and clearance from the liver suggest suitability for diagnostic studies and for prospective dosimetry for 67Cu-SARTATE peptide receptor radionuclide therapy, and the half-life of 64Cu would also facilitate good-manufacturing-practice production and distribution to sites without access to 68Ga.

Original languageEnglish
Pages (from-to)777-785
Number of pages9
JournalJournal of Nuclear Medicine
Volume60
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019

Keywords

  • Copper-64
  • Neuroendocrine tumor
  • Peptide receptor radionuclide therapy
  • Positron emission tomography
  • Radiopharmaceuticals
  • Theranostics

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