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

⁶⁸Ga-NODAGA-LM3 (where LM3 is p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH₂) 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. Methods: Patients were equally randomized into 2 arms, with arm A receiving ⁶⁸Ga-NODAGA-LM3 and arm B receiving ⁶⁸Ga-DOTA-LM3. Serial PET scans were acquired at 5, 15, 30, 45, 60, and 120 min after ⁶⁸Ga-NODAGA-LM3 (200 MBq ± 11 MBq/40 μg of total peptide mass) or ⁶⁸Ga-DOTA-LM3 (172 MBq ± 21 MBq/40 μg of 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 (grade 2), and one of them had vomiting (grade 1). The PET images of the Other 14 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 than with ⁶⁸Ga-NODAGA-LM3. In total, 38 lesions were analyzed, including 18 with ⁶⁸Ga-NODAGA-LM3 and 20 with 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 min to 74.6 ± 56.3 at 2 h. With ⁶⁸Ga-DOTA-LM3, the tumor uptake rapidly reached a high level at 5 min after injection, with an average SUV_max of 36.6 ± 23.6, and continued to increase to 45.3 ± 29.3 until 30 min after injection. The urinary bladder wall was 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 are comparable to those for Other ⁶⁸Ga-labeled SSTR2 antagonists. Further studies are required to look into the potential antagonistic effects of ⁶⁸Ga-NODAGA-LM3 and ⁶⁸Ga-DOTA-LM3.

68Ga-DOTA-LM3; 68Ga-NODAGA-LM3; PET/CT; neuroendocrine tumor; somatostatin receptor antagonist.