Mathias C J, Wang S, Waters D J, Turek J J, Low P S, Green M A
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-1333, USA.
J Nucl Med. 1998 Sep;39(9):1579-85.
Indium-111-labeled diethylenetriamine pentaacetic acid (DTPA)-folate was evaluated as a radiopharmaceutical for targeting tumor-associated folate receptors.
Athymic mice were subcutaneously inoculated with approximately 1.8 x 10(6) folate receptor-positive KB (human nasopharyngeal carcinoma) cells, yielding 0.2- to 0.6-g tumors in 15 days, at which time (111)In-DTPA-folate, (111)In-DTPA or (111)In-citrate was administered by intravenous injection.
The (111)In-DTPA-folate conjugate afforded marked tumor-specific (111)In deposition in vivo using this mouse model. The involvement of the folate receptor in mediating tumor uptake of (111)In-DTPA-folate was demonstrated by the blocking of tumor uptake by coadministration of free folic acid (intravenous). The (111)In-DTPA-folate also shows folate receptor-mediated uptake and retention in the kidneys, presumably reflecting radiotracer binding to folate receptors of the proximal tubules. In control experiments, the (111)In-citrate radiopharmaceutical precursor was also shown to afford significant tumor uptake of (111)In, but with much poorer tumor-to-background tissue contrast than that obtained with (111)In-DTPA-folate. Unconjugated (111)In-DTPA showed no tumor affinity.
Indium-111-DTPA-folate appears suitable as a radiopharmaceutical for targeting tumor-associated folate receptors.
评估了铟 - 111标记的二乙烯三胺五乙酸（DTPA） - 叶酸作为一种靶向肿瘤相关叶酸受体的放射性药物。
将约1.8×10⁶个叶酸受体阳性的KB（人鼻咽癌）细胞皮下接种到无胸腺小鼠体内，15天后形成0.2至0.6克的肿瘤，此时通过静脉注射给予铟 - 111 - DTPA - 叶酸、铟 - 111 - DTPA或铟 - 111 - 柠檬酸盐。
使用该小鼠模型，铟 - 111 - DTPA - 叶酸偶联物在体内实现了显著的肿瘤特异性铟沉积。通过静脉共同给予游离叶酸来阻断肿瘤摄取，证明了叶酸受体在介导铟 - 111 - DTPA - 叶酸的肿瘤摄取中的作用。铟 - 111 - DTPA - 叶酸在肾脏中也显示出叶酸受体介导的摄取和滞留，推测这反映了放射性示踪剂与近端小管的叶酸受体结合。在对照实验中，铟 - 111 - 柠檬酸盐放射性药物前体也显示出显著的铟肿瘤摄取，但与铟 - 111 - DTPA - 叶酸相比，肿瘤与背景组织的对比度要差得多。未偶联的铟 - 111 - DTPA没有肿瘤亲和力。
铟 - 111 - DTPA - 叶酸似乎适合作为一种靶向肿瘤相关叶酸受体的放射性药物。
