PDF(Pubmed)
Abstract：
Gastrin-releasing peptide receptors (GRPRs) are overexpressed in the majority of primary prostate tumors and in prostatic lymph node and bone metastases. Several GRPR antagonists were developed for SPECT and PET imaging of prostate cancer. We previously reported a preclinical evaluation of the GRPR antagonist [99mTc]Tc-maSSS-PEG2-RM26 (based on [D-Phe6, Sta13, Leu14-NH2]BBN(6-14)) which bound to GRPR with high affinity and had a favorable biodistribution profile in tumor-bearing animal models. In this study, we aimed to prepare and test kits for prospective use in an early-phase clinical study. The kits were prepared to allow for a one-pot single-step radiolabeling with technetium-99m pertechnetate. The kit vials were tested for sterility and labeling efficacy. The radiolabeled by using the kit GRPR antagonist was evaluated in vitro for binding specificity to GRPR on PC-3 cells (GRPR-positive). In vivo, the toxicity of the kit constituents was evaluated in rats. The labeling efficacy of the kits stored at 4 °C was monitored for 18 months. The biological properties of [99mTc]Tc-maSSS-PEG2-RM26, which were obtained after this period, were examined both in vitro and in vivo. The one-pot (gluconic acid, ethylenediaminetetraacetic acid, stannous chloride, and maSSS-PEG2-RM26) single-step radiolabeling with technetium-99m was successful with high radiochemical yields (>97%) and high molar activities (16-24 MBq/nmol). The radiolabeled peptide maintained its binding properties to GRPR. The kit constituents were sterile and non-toxic when tested in living subjects. In conclusion, the prepared kit is considered safe in animal models and can be further evaluated for use in clinics.
摘要：
胃泌素释放肽受体（GRPR）在大多数原发性前列腺肿瘤以及前列腺淋巴结和骨转移中过度表达。开发了几种GRPR拮抗剂用于前列腺癌的SPECT和PET成像。我们先前报道了GRPR拮抗剂[99mTc]Tc-maSSS-PEG2-RM26（基于[D-Phe6，Sta13，Leu14-NH2]BBN（6-14））的临床前评估，该药物以高亲和力与GRPR结合并在荷瘤动物模型中具有良好的生物分布特征。在这项研究中,我们的目标是准备和测试试剂盒,以便在早期临床研究中前瞻性使用.制备试剂盒以允许用99m高tech酸盐进行一锅单步放射性标记。测试试剂盒小瓶的无菌性和标记功效。在体外评估通过使用试剂盒GRPR拮抗剂放射性标记的对PC-3细胞(GRPR阳性)上GRPR的结合特异性。在体内,在大鼠中评估试剂盒成分的毒性。监测在4°C下储存的试剂盒的标记功效18个月。[99mTc]Tc-maSSS-PEG2-RM26的生物学特性,在体外和体内检查。一罐(葡萄糖酸，乙二胺四乙酸,氯化亚锡,和maSSS-PEG2-RM26）用99m进行的一步放射性标记成功，具有高的放射化学产率（>97％）和高的摩尔活性（16-24MBq/nmol）。放射性标记的肽保持其与GRPR的结合特性。当在活体受试者中测试时,试剂盒成分是无菌且无毒的。总之,所制备的试剂盒在动物模型中被认为是安全的，可以进一步评估用于临床。
