DOTA-D-Tyr1-octreotate:: A somatostatin analogue for labeling with metal and halogen radionuclides for cancer imaging and therapy
DOTA-D-Tyr1-octreotate:: A somatostatin analogue for labeling with metal and halogen radionuclides for cancer imaging and therapy
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DOI：
10.1021/bc015590k
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发表时间：
2002-07-01
影响因子：
4.7
通讯作者：
Anderson, CJ
中科院分区：
文献类型：
--
作者：
Li, WP;Lewis, JS;Anderson, CJ
本研究的目的是评价一种生长抑素受体配体DOTA-D-Tyr(1)-octreotate (DOTA- dy1 - tate)，该配体具有螯合剂1,4,7,10-四氮杂环十四烷-N，N,N ‘，N’ -四乙酸（DOTA）附着在D-Tyr(1)残基上，可以用放射性卤素和放射性金属进行放射性标记。将螯合剂附着在Tyr(1)残基上的一个潜在优点是，卤素放射性标记可能残留或滞留在肿瘤细胞中，而不是从肿瘤中清除。采用固相法合成了DOTA-DY1-TATE，并用(CU)-C-61、CU -64和I-125进行了放射性标记，具有较高的放射化学纯度和比活性。竞争结合实验表明，Cu-nat-DOTA-DY1-TATE和DOTA-I-nat-DY1-TATE在AR42J大鼠胰腺肿瘤细胞膜上与in -nat- dtpa - oc具有相当的亲和力。Cu-61-DOTA-DY1-TATE的解离常数K-d为176.4 pM，受体浓度B-max为244.4 fmol/mg。注射后1 h， AR42J荷瘤Lewis大鼠体内Cu-64-DOTA-DY1-TATE的肿瘤摄取率为1.515% ID/g， DOTA-I-125-DY1-TATE的肿瘤摄取率为0.814% ID/g。注射后4小时，DOTA-I-125-DY1-TATE仍在肿瘤中以较高的浓度存在，提示碘可能残留在肿瘤细胞中。注射后2 h， AR42J荷瘤大鼠和SCID小鼠的Cu-64-DOTA-DY1-TATE的MicroPET成像显示，Cu-64-DOTA-DY1-TATE在大鼠模型的大腿肿瘤和小鼠的颈部和大腿肿瘤中有明显的摄取和良好的对比。本研究表明，DOTA-DY1-TATE是一种生长抑素类似物，可以用金属和卤素放射性核素标记，其cu -64和i -125放射性标记的化合物在正常和肿瘤组织中显示出生长抑素受体介导的摄取。
The goal of this study was to evaluate a somatostatin receptor ligand, DOTA-D-Tyr(1)-octreotate (DOTA-DY1-TATE), that has the chelator 1,4,7,10-tetraazacyclotetradecane-N,N,N",N'"-tetraacetic acid (DOTA) attached to the D-Tyr(1) residue, allowing radiolabeling with both radiohalogens and radiometals. A potential advantage of having a chelator attached to the Tyr(1) residue is that halogen radiolabels may residualize or remain trapped in tumor cells rather than clear from the tumor. DOTA-DY1-TATE was synthesized by solid-phase methods and radiolabeled with (CU)-C-61, Cu-64, and I-125 in high radiochemical purity and specific activity. A competitive binding assay demonstrated that Cu-nat-DOTA-DY1-TATE and DOTA-I-nat-DY1-TATE had comparable affinity to In-nat-DTPA-OC in AR42J rat pancreatic tumor cells membranes. Cu-61-DOTA-DY1-TATE had a dissociation constant (K-d) of 176.4 pM and a receptor concentration (B-max) of 244.4 fmol/mg. A tumor uptake of 1.515 %ID/g was determined for Cu-64-DOTA-DY1-TATE and 0.814 %ID/g for DOTA-I-125-DY1-TATE in AR42J tumor bearing Lewis rats at 1 h postinjection. DOTA-I-125-DY1-TATE remained in the tumor at a higher concentration out to 4 h postinjection, suggesting that the iodine may have residualized in the tumor cells. MicroPET imaging of Cu-64-DOTA-DY1-TATE in AR42J tumor bearing rats and SCID mice at 2 h postinjection showed significant uptake and good contrast in the thigh tumors in the rat model and in the neck and thigh tumors of the mouse. This study demonstrates that DOTA-DY1-TATE is a somatostatin analogue that can be labeled with both metal and halogen radionuclides, and its Cu-64-and I-125-radiolabeled compounds showed somatostatin receptor-mediated uptake in normal and tumor tissues.