Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients
Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients
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DOI：
10.2967/jnumed.107.049452
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发表时间：
2008-06-01
影响因子：
9.3
通讯作者：
Aboagye, Eric O.
中科院分区：
文献类型：
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作者：
Kenny, Laura M.;Coombes, R. Charles;Aboagye, Eric O.
整合素α(V)β(3)受体在肿瘤细胞和血管内皮细胞上表达上调，在血管生成和转移中发挥重要作用。精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp，RGD)多肽配体对这些整合素具有很高的亲和力，可用于PET：血管生成或肿瘤发展的成像。我们评估了一种新的放射性标记的基于RGD的整合素多肽-聚合物结合物AH111585的安全性、稳定性和肿瘤分布动力学，以及它用于PET检测转移性乳腺癌患者肿瘤的可行性。方法：应用正电子发射计算机断层扫描(PET)技术检测7例转移性乳腺癌患者的18个肿瘤病灶中(18)FAH111585的生物分布，并与CT结果进行比较。血浆样品层析法测定F-18-AH 111585的代谢稳定性。肿瘤和正常组织的PET图像上的感兴趣区(ROI)被用来确定组织中放射性配基结合的动力学。结果：所有患者对放射药物和正电子发射计算机断层扫描的耐受性良好。CT检测到的所有18个肿瘤在F-18-AH111585 PET图像上均可见，要么与周围正常组织相比摄取明显增加，要么在肝转移的情况下，由于正常肝组织的高本底活度，作为摄取不足的区域。F-18-AH111585要么均匀分布在肿瘤内，要么出现在肿瘤边缘，与肿瘤周围存活的肿瘤和伴随血管生成的中央坏死的模式一致。肺转移瘤、胸膜转移瘤、骨转移瘤、淋巴结转移瘤和原发肿瘤的摄取增加(P=0.002)。结论：(BF)-B-18-AH111585与α(V)-β(3)整合素结合是安全的，代谢稳定，可保留在肿瘤组织中，PET可在大多数解剖部位检测乳腺癌病变。
The integrin alpha(v)beta(3) receptor is upregulated on tumor cells and endothelium and plays important roles in angiogenesis and metastasis. Arg-Gly-Asp (RGD) peptide ligands have high affinity for these integrins and can be radiolabeled for PET :imaging of angiogenesis or tumor development. We have assessed the safety, stability, and tumor distribution kinetics of a novel radiolabeled RGD-based integrin peptide-polymer conjugate, AH111585, and its feasibility to detect tumors in metastatic breast cancer patients using PET. Methods: The biodistribution of (18)FAH111585 was assessed in 18 tumor lesions from 7 patients with metastatic breast cancer by PET, and the PET data were compared with CT results. The metabolic stability of F-18-AH 111585 was assessed by chromatography of plasma samples. Regions of interest (ROIs) defined over tumor and normal tissues of the PET images were used to determine the kinetics of radioligand binding in tissues. Results: The radiopharmaceutical and PET procedures were well tolerated in all patients. All 18 tumors detected by CT were visible on the F-18-AH111585 PET images, either as distinct increases in uptake compared with the surrounding normal tissue or, in the case of liver metastases, as regions of deficit uptake because of the high background activity in normal liver tissue. F-18-AH111585 was either homogeneously distributed in the tumors or appeared within the tumor rim, consistent with the pattern of viable peripheral tumor and central necrosis often seen in association with angiogenesis. Increased uptake compared with background (P = 0.002) was demonstrated in metastases in lung, pleura, bone, lymph node, and primary tumor. Conclusion: (BF)-B-18-AH111585 designed to bind the alpha(v)beta(3) integrin is safe, metabolically stable, and retained in tumor tissues and detects breast cancer lesions by PET in most anatomic sites.