Institute of Nuclear Energy Research, Taoyuan, Taiwan, ROC.
Anticancer Res. 2010 Oct;30(10):4039-48.
AMBA (DO3A-CH(2)CO-G-(4-aminobenzoyl)-QWAVGHLM-NH(2)) is a bombesin (BN)-like peptide having high affinity with gastrin-releasing peptide receptors (GRPr).(177)Lu-AMBA is currently undergoing clinical trial as a systemic radiotherapy for hormone refractory prostate cancer (HRPC) patients. This study evaluated the biodistribution, pharmacokinetics, bioluminescent imaging (BLI) and microSPECT/CT imaging of (177)Lu-AMBA in PC-3M-luc-C6 luciferase-expressing human prostate tumour-bearing mice. Plasma stability of (177)Lu-AMBA could be maintained up to 55.67±6.07% at 24 h in a protection buffer. High positive correlations of PC-3M luc-C6 tumour growth in SCID mice between caliper measurement and BLI were observed (R(2)=0.999). Both the biodistribution and microSPECT/CT imaging in PC-3M-luc-C6 bearing-tumour mice showed that (177)Lu-AMBA in tumour uptake could be retained for 24 h. The distribution half-life (t(1/2α)) and the elimination half-life (t(1/2β)) of (177) Lu-AMBA in mice were 0.52 h and 26.6 h, respectively. These results indicated that BLI could be used to monitor the growth of tumour. High uptake of (177)Lu-AMBA in PC-3M-luc-C6 tumour-bearing mice by microSPECT/CT imaging can further evaluate the potential of (177)Lu-AMBA therapy for PC-3M-luc-C6 tumours.
AMBA（DO3A-CH(2)CO-G-(4-aminobenzoyl)-QWAVGHLM-NH(2)）是一种具有高亲和力与胃泌素释放肽受体（GRPr）的蛙皮素（BN）样肽。(177)Lu-AMBA 目前正在作为一种针对激素难治性前列腺癌（HRPC）患者的全身放射治疗进行临床试验。本研究评估了（177）Lu-AMBA 在表达荧光素酶的人前列腺肿瘤 PC-3M-luc-C6 荷瘤小鼠中的生物分布、药代动力学、生物发光成像（BLI）和 microSPECT/CT 成像。在保护缓冲液中，（177）Lu-AMBA 的血浆稳定性在 24 小时内可保持在 55.67±6.07%。在 SCID 小鼠中，PC-3M luc-C6 肿瘤生长的卡尺测量与 BLI 之间存在高度正相关（R(2)=0.999）。PC-3M-luc-C6 荷瘤小鼠的生物分布和 microSPECT/CT 成像均显示，肿瘤摄取的（177）Lu-AMBA 可在 24 小时内保留。（177）Lu-AMBA 在小鼠体内的分布半衰期（t(1/2α)）和消除半衰期（t(1/2β)）分别为 0.52 h 和 26.6 h。这些结果表明，BLI 可用于监测肿瘤的生长。microSPECT/CT 成像显示，（177）Lu-AMBA 在 PC-3M-luc-C6 荷瘤小鼠中的高摄取可进一步评估（177）Lu-AMBA 治疗 PC-3M-luc-C6 肿瘤的潜力。
