(18)F, (64)Cu, and (68)Ga labeled RGD-bombesin heterodimeric peptides for PET imaging of breast cancer.
(18)F, (64)Cu, and (68)Ga labeled RGD-bombesin heterodimeric peptides for PET imaging of breast cancer.
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DOI：
10.1021/bc9000245
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发表时间：
2009-05-20
影响因子：
4.7
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Liu Z;Yan Y;Liu S;Wang F;Chen X
放射性标记的RGD和蛙皮素（BBN）放射性示踪剂特异性靶向整合素αvβ3和胃泌素释放肽受体（GRPR），这两种放射性示踪剂都是用于肿瘤成像的有前景的放射性药物。我们最近设计并合成了一个RGD-BBN异二聚体肽，在一个单一的分子中具有RGD和BBN基序。18F标记的RGD-BBN异二聚体在PC-3前列腺癌模型中表现出整合素αvβ3和GRPR双重靶向。在这项研究中，我们研究了放射性标记的RGD-BBN示踪剂是否可以用于使用microPET检测乳腺癌。细胞结合试验表明，高表达GRPR的乳腺癌细胞通常表达低至中等水平的整合素αvβ3，而高表达整合素αvβ3的乳腺癌细胞具有可忽略的GRPR水平。我们用三种正电子放射性核素18F、64 Cu和68 Ga标记RGD-BBN异二聚体，并在原位T47 D（GRPR+/低整合素αvβ3）和MDA-MB-435（GRPR−/整合素αvβ3+）乳腺癌模型中研究相应的PET放射性示踪剂。三种放射性示踪剂均具有体外整合素αvβ3和GRPR结合的双重亲和力。相对于相应的BBN类似物，RGD-BBN放射性示踪剂在MDA-MB-435（GRPR−/整合素αvβ3+）肿瘤成像方面的优势是显而易见的。18F-FB-PEG 3-RGD-BBN显示出比64 Cu-NOTA-RGD-BBN和68 Ga-NOTA-RGD-BBN更低的肿瘤摄取，但能够以高对比度可视化乳腺癌肿瘤。64 Cu-NOTA-RGD-BBN和68 Ga-NOTA-RGD-BBN的合成比18F-FB-PEG 3-RGD-BBN快得多且容易得多。64 Cu-NOTA-RGD-BBN显示出延长的肿瘤摄取，但也比68 Ga-NOTA-RGD-BBN和18F-FB-PEG 3-RGD-BBN显示出更高的肝脏保留和肾脏摄取。68 Ga-NOTA-RGD-BBN具有高肿瘤信号，但与其他两种放射性示踪剂相比也具有相对较高的背景摄取。总之，辅标记基团、螯合剂和同位素都对RGD-BBN示踪剂用于双重整合素和GRPR识别的肿瘤靶向功效和体内动力学具有深远影响。进一步开发适当标记的RGD-BBN示踪剂用于癌症的PET成像是必要的。
Radiolabeled RGD and bombesin (BBN) radiotracers that specifically target integrin αvβ3 and gastrin releasing peptide receptor (GRPR) are both promising radiopharmaceuticals for tumor imaging. We recently designed and synthesized a RGD-BBN heterodimeric peptide with both RGD and BBN motifs in one single molecule. The 18F-labeled RGD-BBN heterodimer exhibited dual integrin αvβ3 and GRPR targeting in a PC-3 prostate cancer model. In this study we investigated whether radiolabeled RGD-BBN tracers can be used to detect breast cancer by using microPET. Cell binding assay demonstrated that the high GRPR expressing breast cancer cells typically express low to moderate level of integrin αvβ3, while high integrin αvβ3 expressing breast cancer cells have negligible level of GRPR. We labeled RGD-BBN heterodimer with three positron emitting radionuclides 18F, 64Cu and 68Ga, and investigated the corresponding PET radiotracers in both orthotopic T47D (GRPR+/low integrin αvβ3) and MDA-MB-435 (GRPR−/integrin αvβ3+) breast cancer models. The three radiotracers all possessed in vitro dual integrin αvβ3 and GRPR binding affinity. The advantages of the RGD-BBN radiotracers over the corresponding BBN analogues are obvious for imaging MDA-MB-435 (GRPR−/integrin αvβ3+) tumor. 18F-FB-PEG3-RGD-BBN showed lower tumor uptake than 64Cu-NOTA-RGD-BBN and 68Ga-NOTA-RGD-BBN but was able to visualize breast cancer tumors with high contrast. Synthesis of 64Cu-NOTA-RGD-BBN and 68Ga-NOTA-RGD-BBN is much faster and easier than 18F-FB-PEG3-RGD-BBN. 64Cu-NOTA-RGD-BBN showed prolonged tumor uptake, but also higher liver retention and kidney uptake than 68Ga-NOTA-RGD-BBN and 18F-FB-PEG3-RGD-BBN. 68Ga-NOTA-RGD-BBN possessed high tumor signals, but also relatively high background uptake as compared with the other two radiotracers. In summary, the prosthetic labeling groups, chelators and isotopes all have profound effect on the tumor targeting efficacy and in vivo kinetics of the RGD-BBN tracers for dual integrin and GRPR recognition. Further development of suitably labeled RGD-BBN tracers for PET imaging of cancer is warranted.
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影响因子：
3.1
作者：
Chen, XY;Liu, S;Conti, PS
通讯作者：
Conti, PS
影响因子：
9.3
作者：
Kenny, Laura M.;Coombes, R. Charles;Aboagye, Eric O.
通讯作者：
Aboagye, Eric O.
影响因子：
9.3
作者：
Dimitrakopoulou-Strauss, Antonia;Hohenberger, Peter;Strauss, Ludwig G.
通讯作者：
Strauss, Ludwig G.
影响因子：
2.8
作者：
CLARKE, ET;MARTELL, AE
通讯作者：
MARTELL, AE
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA