Ranjbar Saeid, Aghamiri Seyed Mahmoud Reza, Rajabifar Saeed, Zolghadri Samaneh, Yousefnia Hassan
Department of Radiation Medicine Engineering, Shahid Beheshti University, Tehran, Iran.
Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.
Phys Eng Sci Med. 2025 Mar;48(1):273-283. doi: 10.1007/s13246-024-01510-0. Epub 2025 Jan 6.
Gastrin-releasing peptide receptors (GRPRs) overexpressed in many cancers are known as promising biomarkers to target tumors such as prostate, breast, and lung cancers. As the early diagnosis of the cancers can serve for better treatment of the patients, [In]In-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ([In]In-RM2) was prepared using an in-house developed Sn/In generator. 0.05 M HCl was chosen as the best solution for the generator elution, and 3rd-6th fractions of the generator with the highest activity concentration were used. The chemical, radiochemical, and radionuclide purities of the eluted [In]InCl were studied using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), radio thin layer chromatography (RTLC), and gamma spectrometry methods, respectively. The radiolabeled peptide was prepared in optimal conditions and the radiochemical purity (RCP) was investigated by RTLC and high-performance liquid chromatography (HPLC) methods. After stability and lipophilicity assessments, the biodistribution of the final complex was checked in normal animals by imaging and scarification. [In]In-RM2 was prepared with RCP > 99% (RTLC and HPLC), and specific activity of 43.2 TBq/mmol at optimal labeling conditions. The complex was stable in human serum and PBS buffer for at least 3 h (RCP > 96%). The partition coefficient showed the hydrophilic nature of the complex which results in the fast blood clearance via urinary tract. The biodistribution studies was demonstrated high accumulation of [In]In-RM2 in GRPR-expressing tissues. The results showed [In]In-RM2 can be considered a high-potential agent for SPECT imaging of GRPR-expressing cancers.
胃泌素释放肽受体（GRPRs）在许多癌症中过表达，是靶向前列腺癌、乳腺癌和肺癌等肿瘤的有前景的生物标志物。由于癌症的早期诊断有助于更好地治疗患者，使用内部开发的Sn/In发生器制备了[铟-111]In-DOTA-哌啶-D-苯丙氨酸-谷氨酰胺-色氨酸-丙氨酸-缬氨酸-甘氨酸-组氨酸-司他丁-亮氨酸-氨基（[铟-111]In-RM2）。选择0.05 M盐酸作为发生器洗脱的最佳溶液，并使用活性浓度最高的发生器第3至6馏分。分别采用电感耦合等离子体质谱（ICP-MS）、放射性薄层色谱（RTLC）和γ能谱法研究洗脱的[铟-111]InCl的化学纯度、放射化学纯度和放射性核素纯度。在最佳条件下制备放射性标记肽，并通过RTLC和高效液相色谱（HPLC）法研究放射化学纯度（RCP）。在进行稳定性和亲脂性评估后，通过成像和解剖检查正常动物体内最终复合物的生物分布。[铟-111]In-RM2在最佳标记条件下制备，RCP>99%（RTLC和HPLC），比活度为43.2 TBq/mmol。该复合物在人血清和PBS缓冲液中至少3小时保持稳定（RCP>96%）。分配系数表明该复合物具有亲水性，导致其通过尿路快速清除血液。生物分布研究表明[铟-111]In-RM2在表达GRPR的组织中高度蓄积。结果表明，[铟-111]In-RM2可被视为用于表达GRPR癌症的SPECT成像的高潜力试剂。
