Iranian Journal of Nuclear Medicine

Iranian Journal of Nuclear Medicine

Development and evaluation of [64Cu]Cu-DOTATATE for clinical applications

Document Type : Original Article

Authors
Samaneh Zolghadri 1
Fateme Badipa 1
Naeimeh Amraee 1
Behrouz Alirezapour 1
Davood Beiki 2
Hassan Yousefnia 1
1 Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran
2 Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
10.22034/irjnm.2023.129117.1543
Abstract
Introduction: Peptide-based radiopharmaceuticals have great advantages that make them one of the most interesting radiotracers for theranostic applications. This study aims to develop [64Cu]Cu-DOTATATE as a beneficial agent for PET imaging of neuroendocrine tumors (NETs).
Methods: 64Cu was produced via 68Zn(p,αn)64Cu reaction using 30 MeV Cyclotron. [64Cu]Cu-DOTATATE was prepared at optimized labeling conditions by varying parameters. The radiochemical purity of [64Cu]Cu-DOTATATE was checked by various methods. The stability of the final radiolabeled compound was assessed in PBS buffer and human serum. Binding affinity and internalization rate of [64Cu]Cu-DOTATATE were studied on the Rat C6 glioma cell line.  The biodistribution of [64Cu]Cu-DOTATATE was studied in normal and tumor-bearing rats at different intervals. Finally, the images were taken after the administration of the radiopharmaceutical by a dual-head SPECT system.
Results: [64Cu]Cu-DOTATATE was produced with radiochemical purity >99% (RTLC & HPLC) and specific activity of 22.4 GBq/mg in optimized conditions. [64Cu]Cu-DOTATATE demonstrated high stability in vitro and in vivo. The binding studies showed a high binding affinity of the radiopharmaceutical to somatostatin-receptor-expressing cells. The internalization studies showed >58% of the radiopharmaceutical is internalized into the C6 cells within 6 h after incubation. The biodistribution of [64Cu]Cu-DOTATATE in normal and tumor-bearing rats showed high uptake of somatostatin-receptor-expressing organs and tumors, respectively. The images of tumor-bearing rats were consistent with the results of the biodistribution study.
Conclusion: Preclinical studies of [64Cu]Cu-DOTATATE showed that the radiopharmaceutical has a high potential for domestic use in  PET imaging of patients with NETs.
Keywords
Copper-64
Radiolabeled peptide
DOTATATE
PET-CT
Subjects
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