RT Journal Article SR Electronic T1 Imaging CXCR4 Expression in Human Cancer Xenografts: Evaluation of Monocyclam 64Cu-AMD3465 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 986 OP 993 DO 10.2967/jnumed.110.085613 VO 52 IS 6 A1 Ravindra A. De Silva A1 Kevin Peyre A1 Mrudula Pullambhatla A1 James J. Fox A1 Martin G. Pomper A1 Sridhar Nimmagadda YR 2011 UL http://jnm.snmjournals.org/content/52/6/986.abstract AB 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.