A Prospective Randomized, Double-blind Study to Evaluate the Safety, Biodistribution, and Dosimetry of ⁶⁸Ga-NODAGA-LM3 and ⁶⁸Ga-DOTA-LM3 in Patients with Well-differentiated Neuroendocrine Tumors

Abstract

Purpose: ⁶⁸Ga-NODAGA-LM3 and ⁶⁸Ga-DOTA-LM3 are somatostatin receptor subtype 2 (SSTR2) specific antagonists used for PET/CT imaging. The purpose of this study was to evaluate the safety, biodistribution, and dosimetry of ⁶⁸Ga-NODAGA-LM3 and ⁶⁸Ga-DOTA-LM3 in patients with well-differentiated neuroendocrine tumors (NETs). Methods: Patients were equally randomized into two arms: Arm A, ⁶⁸Ga-NODAGA-LM3; Arm B, ⁶⁸Ga-DOTA-LM3. Serial PET scans were acquired at 5, 15, 30, 45, 60, and 120 minutes after ⁶⁸Ga-NODAGA-LM3 (200 MBq ± 11 MBq/40 μg total peptide mass) or ⁶⁸Ga-DOTA-LM3 (172 MBq ± 21 MBq/40 μg total peptide mass) injection. The biodistribution in normal organs, tumor uptake, and safety were assessed. Radiation dosimetry was calculated using OLINDA/EXM (version 1.0). Results: Sixteen patients, 8 in each arm, were recruited in the study. Both tracers were well tolerated in most patients. Two patients in Arm B had nausea (G2) and one of them had vomiting (G1). The PET images of other fourteen patients were further analyzed. Significantly lower organ uptake was observed in the pituitary, parotids, liver, spleen, pancreas, adrenal, stomach, small intestine, and kidneys with ⁶⁸Ga-DOTA-LM3 compared to ⁶⁸Ga-NODAGA-LM3. A total of 38 lesions were analyzed, including 18 lesions on ⁶⁸Ga-NODAGA-LM3 and 20 lesions on ⁶⁸Ga-DOTA-LM3. Both tracers showed good tumor uptake and retention. With ⁶⁸Ga-NODAGA-LM3, the tracer accumulation in tumor lesions increased by 138%, from an average SUV_max of 31.3 ± 19.7 at 5 minutes to 74.6 ± 56.3 at 2h. With ⁶⁸Ga-DOTA-LM3, the tumor uptake rapidly reached a high level at 5 minutes after injection, with an average SUV_max of 36.6 ± 23.6, and continued to increase to 45.3 ± 29.3 until 30 minutes post-injection. Urinary bladder wall is the organ receiving the highest absorbed dose in both arms. The mean effective dose was 0.026 ± 0.003 mSv/MBq for ⁶⁸Ga-NODAGA-LM3 and 0.025 ± 0.002 mSv/MBq for ⁶⁸Ga-DOTA-LM3. Conclusion: Both ⁶⁸Ga-NODAGA-LM3 and ⁶⁸Ga-DOTA-LM3 show favorable biodistribution, high tumor uptake, and good tumor retention, resulting in high image contrast. The dosimetric data is comparable to other ⁶⁸Ga-labeled SSTR2 antagonists. Further studies are required to look into the potential antagonistic effects of ⁶⁸Ga-NODAGA-LM3 and ⁶⁸Ga-DOTA-LM3.