Department of Chemistry, Faculty of Art and Science, Celal Bayar University, Manisa, Turkey.
Cancer Biother Radiopharm. 2012 Aug;27(6):371-83. doi: 10.1089/cbr.2011.1157. Epub 2012 Jun 12.
Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with (131)I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that (131)I-labeled BLMG ((131)I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of (131)I-BLM and (131)I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that (131)I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, (131)I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications.
博来霉素葡萄糖醛酸苷（BLMG）是博来霉素的葡萄糖醛酸缀合物。在本研究中，主要通过使用大鼠肝脏分离的微粒体制剂，用碘代法用（131）I 标记来酶促合成 BLMG，目的是生成放射性标记的前药，并研究其与荷瘤 Balb/C 小鼠的生物亲和力。使用薄层层析放射色谱法和高效液相色谱法进行质量控制程序。通过 following Caco-2 细胞接种到小鼠中进行肿瘤生长。放射性标记产率约为 65%。结果表明，（131）I 标记的 BLMG（（131）I-BLMG）在人血清中 24 小时内高度稳定。用雄性白化 Wistar 大鼠和结直肠腺癌荷瘤雌性 Balb/C 小鼠进行生物分布研究。在大鼠中的生物分布结果表明，前列腺、大肠和脊髓的摄取率很高。此外，闪烁照相研究结果与生物分布研究结果一致。荷瘤小鼠的异种移植研究表明，（131）I-BLM 和（131）I-BLMG 在注射后 30 分钟内对肿瘤的摄取率很高。荷瘤动物研究表明，（131）I-BLMG 特别保留在结直肠腺癌中，具有高肿瘤摄取率。因此，（131）I-BLMG 可以被证明是一种有前途的成像和治疗剂，特别是在核医学应用中用于结肠癌。
