Radiopharmaceutical Sciences Institute, 143 Major Hall, University of Missouri, Columbia, MO 65211, USA.
Anticancer Res. 2010 Jan;30(1):19-30.
Gastrin-releasing peptide (GRP) receptors are overexpressed on a variety of human carcinomas, including those of the breast. These receptors may be targeted with bombesin (BBN), which binds to GRP receptors with high affinity and specificity. The aim of this study was to develop a (99m)Tc(I)-BBN analog with favorable pharmacokinetic properties in order to improve the visualization of breast cancer tissue.
Solid-phase peptide synthesis was used to produce a series of X-Y-BBN-NH2 conjugates, where X is pyrazolyl (PZ1) or 2,3-diaminopropionic acid (DPR) and Y is a spacer sequence. Their metallated counterparts were prepared by reacting (99m)Tc-(H(2)O)(3)(CO)(3) with the corresponding ligand.
While the PZ1 conjugates exhibited higher GRP receptor binding affinities in vitro, the DPR analogs demonstrated superior target tissue accumulation and pharmacokinetic properties in vivo.
These results demonstrate the ability of the DPR derivatives (Y=glycylserylglycine, triserine) to clearly identify the T47-D tumor tissue in xenografted SCID mice.
胃泌素释放肽（GRP）受体在多种人类癌瘤中过度表达，包括乳腺癌。这些受体可以与蛙皮素（BBN）结合，BBN 与 GRP 受体具有高亲和力和特异性。本研究旨在开发具有良好药代动力学特性的（99m）Tc（I）-BBN 类似物，以提高乳腺癌组织的可视化程度。
采用固相肽合成法制备了一系列 X-Y-BBN-NH2 缀合物，其中 X 为吡唑基（PZ1）或 2,3-二氨基丙酸（DPR），Y 为间隔序列。通过将相应的配体与 [(99m)Tc-（H2O）（3）（CO）（3)]+反应，制备了它们的金属化对应物。
虽然 PZ1 缀合物在体外表现出更高的 GRP 受体结合亲和力，但 DPR 类似物在体内显示出更好的靶组织积累和药代动力学特性。
这些结果表明 DPR 衍生物（Y=甘氨酰丝氨酰甘氨酸、三丝氨酸）有能力在异种移植的 SCID 小鼠中清晰地识别 T47-D 肿瘤组织。
