Imaging CXCR4 Expression in Human Cancer Xenografts: Evaluation of Monocyclam 64Cu-AMD3465

Journal of Nuclear Medicine

Mrudula Pullambhatla¹  Martin G. Pomper¹  Sridhar Nimmagadda¹  Kevin Peyre¹  Ravindra A. De Silva¹  James J. Fox¹ 

[1] Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland

关键词: PET;    tumor microenvironment;    chemokine;    stem cells;    molecular imaging;    colon cancer;    brain cancer;    metastasis;   

DOI  :  10.2967/jnumed.110.085613

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The chemokine receptor 4 (CXCR4) is overexpressed in several cancers and metastases and as such presents an enticing target for molecular imaging of metastases and metastatic potential of the primary tumor. CXCR4-based imaging agents could also be useful for diagnosis, staging, and therapeutic monitoring. Here we evaluated a positron-emitting monocyclam analog, 64Cu-{N-[1,4,8,11-tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(aminomethyl)pyridine} (64Cu-AMD3465), in subcutaneous U87 brain tumors and U87 tumors stably expressing CXCR4 (U87-stb-CXCR4) and in colon tumors (HT-29) using dynamic and whole-body PET supported by ex vivo biodistribution studies. Both dynamic and whole-body PET/CT studies show specific accumulation of radioactivity in U87-stb-CXCR4 tumors, with the percentage injected dose per gram reaching a maximum of 102.70 ± 20.80 at 60 min and tumor-to-muscle ratios reaching a maximum of 362.56 ± 153.51 at 90 min after injection of the radiotracer. Similar specificity was also observed in the HT-29 colon tumor model. Treatment with AMD3465 inhibited uptake of radioactivity by the tumors in both models. Our results show that 64Cu-AMD3465 is capable of detecting lesions in a CXCR4-dependent fashion, with high target selectivity, and may offer a scaffold for the synthesis of clinically translatable agents.

【 授权许可】

Unknown