PT  - JOURNAL ARTICLE
AU  - De Silva, Ravindra A.
AU  - Peyre, Kevin
AU  - Pullambhatla, Mrudula
AU  - Fox, James J.
AU  - Pomper, Martin G.
AU  - Nimmagadda, Sridhar
TI  - Imaging CXCR4 Expression in Human Cancer Xenografts: Evaluation of Monocyclam <sup>64</sup>Cu-AMD3465
AID  - 10.2967/jnumed.110.085613
DP  - 2011 Jun 01
TA  - Journal of Nuclear Medicine
PG  - 986--993
VI  - 52
IP  - 6
4099  - http://jnm.snmjournals.org/content/52/6/986.short
4100  - http://jnm.snmjournals.org/content/52/6/986.full
SO  - J Nucl Med2011 Jun 01; 52
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.