Mazaheri Tehrani Maryam, Erfani Mostafa, Amirmozafari Nour, Nejadsattari Taher
Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran.
Asia Ocean J Nucl Med Biol. 2019 Spring;7(2):172-180. doi: 10.22038/AOJNMB.2019.37712.1251.
Despite recent advances in treatment modalities, cancer remains a major source of morbidity and mortality throughout the world. Currently, the development of sensitive and specific molecular imaging probes for early diagnosis of cancer is still a problematic challenge. Previous studies have been shown that some of the antimicrobial peptides (AMPs) exhibit a broad spectrum of cytotoxic activity against cancerous cells in addition to their antimicrobial activities. MicrocinJ25 (MccJ25) is an antimicrobial peptide that is produced by () strain. The aim of this study was to investigate the potential of a new peptide radiopharmaceutical derived from MccJ25 for diagnosis of melanoma tumor bearing C57BL/6 mice.
A 14 amino acid analog of MccJ25 was labeled with technetium-99m (Tc) through hydrazinonicotinamide (HYNIC) chelator and tricine as coligand. In vivo tumor uptake and tissue distribution were evaluated. The in vivo biodistribution studies were determined in C57BL/6 mice bearing B16F10 tumor.
The amount of non-peptide related Tc-impurities that measured by thin layer chromatography (TLC) did not exceed 5% of the total radioactivity. The in vitro binding to B16F10 cells was 30.73 ± 0.9% after 1 h incubation at 37°C, and saturation binding experiments showed good affinity for radio-complex (K=47.98±6.25 nM). The melanoma tumor was clearly visible up 1 h post-injection by gamma camera imaging.
The results showed that Tc-labeld peptide could be a promising candidate as a targeting radiopharmaceutical for melanoma tumor imaging in mice.
尽管近年来治疗方式取得了进展，但癌症仍是全球发病和死亡的主要原因。目前，开发用于癌症早期诊断的灵敏且特异的分子成像探针仍是一个颇具挑战性的难题。先前的研究表明，一些抗菌肽（AMPs）除了具有抗菌活性外，还对癌细胞表现出广泛的细胞毒性活性。微小菌素J25（MccJ25）是一种由（）菌株产生的抗菌肽。本研究的目的是探讨一种源自MccJ25的新型肽放射性药物用于诊断荷黑素瘤肿瘤的C57BL/6小鼠的潜力。
通过肼基烟酰胺（HYNIC）螯合剂和作为共配体的三羟甲基氨基甲烷将14个氨基酸的MccJ25类似物用99m锝（Tc）标记。评估体内肿瘤摄取和组织分布。在荷B16F10肿瘤的C57BL/6小鼠中进行体内生物分布研究。
通过薄层色谱（TLC）测定的非肽相关Tc杂质的量不超过总放射性的5%。在37°C孵育1小时后，与B16F10细胞的体外结合率为30.73±0.9%，饱和结合实验显示对放射性复合物具有良好的亲和力（K = 47.98±6.25 nM）。注射后1小时通过γ相机成像可清晰看到黑素瘤肿瘤。
结果表明，Tc标记的肽可能是一种有前景的候选药物，作为小鼠黑素瘤肿瘤成像的靶向放射性药物。
