Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, CAMS and PUMC, Beijing, China.
Department of Oncology, Peking Union Medical College Hospital, Beijing, China.
J Nucl Med. 2021 Oct;62(10):1398-1405. doi: 10.2967/jnumed.120.253096. Epub 2021 Feb 12.
Ga-NODAGA-LM3 (where LM3 is -Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH) and Ga-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 Ga-NODAGA-LM3 and Ga-DOTA-LM3 in patients with well-differentiated neuroendocrine tumors. Patients were equally randomized into 2 arms, with arm A receiving Ga-NODAGA-LM3 and arm B receiving Ga-DOTA-LM3. Serial PET scans were acquired at 5, 15, 30, 45, 60, and 120 min after Ga-NODAGA-LM3 (200 MBq ± 11 MBq/40 μg of total peptide mass) or Ga-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). 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 Ga-DOTA-LM3 than with Ga-NODAGA-LM3. In total, 38 lesions were analyzed, including 18 with Ga-NODAGA-LM3 and 20 with Ga-DOTA-LM3. Both tracers showed good tumor uptake and retention. With Ga-NODAGA-LM3, the tracer accumulation in tumor lesions increased by 138%, from an average SUV of 31.3 ± 19.7 at 5 min to 74.6 ± 56.3 at 2 h. With Ga-DOTA-LM3, the tumor uptake rapidly reached a high level at 5 min after injection, with an average SUV 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 Ga-NODAGA-LM3 and 0.025 ± 0.002 mSv/MBq for Ga-DOTA-LM3. Both Ga-NODAGA-LM3 and Ga-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 Ga-labeled SSTR2 antagonists. Further studies are required to look into the potential antagonistic effects of Ga-NODAGA-LM3 and Ga-DOTA-LM3.
Ga-NODAGA-LM3（其中 LM3 是 -Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH）和 Ga-DOTA-LM3 是用于正电子发射断层扫描/计算机断层扫描成像的生长抑素受体亚型 2（SSTR2）特异性拮抗剂。本研究旨在评估 Ga-NODAGA-LM3 和 Ga-DOTA-LM3 在分化良好的神经内分泌肿瘤患者中的安全性、生物分布和剂量学。患者被平均随机分为 2 组，组 A 接受 Ga-NODAGA-LM3，组 B 接受 Ga-DOTA-LM3。在 Ga-NODAGA-LM3（200MBq±11MBq/40μg 总肽质量）或 Ga-DOTA-LM3（172MBq±21MBq/40μg 总肽质量）注射后 5、15、30、45、60 和 120min 进行连续 PET 扫描。评估正常器官的生物分布、肿瘤摄取和安全性。使用 OLINDA/EXM（版本 1.0）计算辐射剂量学。研究共招募了 16 名患者，每组 8 名。两种示踪剂在大多数患者中均耐受良好。组 B 的 2 名患者出现恶心（2 级），其中 1 名患者出现呕吐（1 级）。对其他 14 名患者的 PET 图像进行了进一步分析。与 Ga-DOTA-LM3 相比，Ga-NODAGA-LM3 在垂体、腮腺、肝脏、脾脏、胰腺、肾上腺、胃、小肠和肾脏中的器官摄取明显较低。共分析了 38 个病灶，包括 Ga-NODAGA-LM3 18 个和 Ga-DOTA-LM3 20 个。两种示踪剂均显示出良好的肿瘤摄取和保留。使用 Ga-NODAGA-LM3，肿瘤病变中的示踪剂积累增加了 138%，从 5min 时的平均 SUV 值 31.3±19.7 增加到 2h 时的 74.6±56.3。使用 Ga-DOTA-LM3，注射后 5min 肿瘤摄取迅速达到较高水平，平均 SUV 值为 36.6±23.6，并持续增加至 30min 时的 45.3±29.3。在这两个手臂中，膀胱壁是吸收剂量最高的器官。平均有效剂量分别为 Ga-NODAGA-LM3 为 0.026±0.003mSv/MBq，Ga-DOTA-LM3 为 0.025±0.002mSv/MBq。Ga-NODAGA-LM3 和 Ga-DOTA-LM3 均表现出良好的生物分布、高肿瘤摄取和良好的肿瘤保留，从而产生高图像对比度。剂量学数据与其他镓标记的 SSTR2 拮抗剂相当。需要进一步研究 Ga-NODAGA-LM3 和 Ga-DOTA-LM3 的潜在拮抗作用。
