Department of Biomedical Engineering , Univesity of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.
TRACON Pharmaceuticals, Inc. , San Diego , California 92122 , United States.
Mol Pharm. 2018 Jul 2;15(7):2606-2613. doi: 10.1021/acs.molpharmaceut.8b00133. Epub 2018 May 30.
Angiogenesis is widely recognized as one of the hallmarks of cancer. Therefore, imaging and therapeutic agents targeted to angiogenic vessels may be widely applicable in many types of cancer. To this end, the theranostic isotope pair, Y and Y, were used to create a pair of agents for targeted imaging and therapy of neovasculature in murine breast cancer models using a chimeric anti-CD105 antibody, TRC105. Serial positron emission tomography imaging with Y-DTPA-TRC105 demonstrated high uptake in 4T1 tumors, peaking at 9.6 ± 0.3%ID/g, verified through ex vivo studies. Additionally, promising results were obtained in therapeutic studies with Y-DTPA-TRC105, wherein significantly ( p < 0.05) decreased tumor volumes were observed for the targeted treatment group over all control groups near the end of the study. Dosimetric extrapolation and tissue histological analysis corroborated trends found in vivo. Overall, this study demonstrated the potential of the pair Y for theranostics, enabling personalized treatments for cancer.
血管生成被广泛认为是癌症的特征之一。因此，针对血管生成的成像和治疗剂可能在许多类型的癌症中广泛应用。为此，使用放射性核素对 Y 和 Y 进行了治疗诊断配对，并用嵌合抗 CD105 抗体 TRC105 为鼠乳腺癌模型中的新生血管创建了一对用于靶向成像和治疗的试剂。用 Y-DTPA-TRC105 进行的连续正电子发射断层扫描成像显示，在 4T1 肿瘤中摄取率很高，达到 9.6±0.3%ID/g，通过离体研究得到了验证。此外，用 Y-DTPA-TRC105 进行的治疗研究也取得了有希望的结果，在研究接近尾声时，靶向治疗组的肿瘤体积明显（p<0.05）小于所有对照组。剂量外推和组织学分析也证实了体内发现的趋势。总的来说，这项研究证明了 Y 对治疗诊断配对的潜力，为癌症的个性化治疗提供了可能。
