Imaging CXCR4 expression in human cancer xenografts: evaluation of monocyclam 64Cu-AMD3465.

Abstract

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, (64)Cu-{N-[1,4,8,11-tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(aminomethyl)pyridine} ((64)Cu-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 (64)Cu-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.

• Authors: Ravindra A De Silva, Kevin Peyre, Mrudula Pullambhatla, James J Fox, Martin G Pomper, Sridhar Nimmagadda
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 52 Issue 6 Pg. 986-93 (Jun 2011) ISSN: 1535-5667 [Electronic] United States
• PMID: 21622896 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CXCR4 protein, mouse
• Copper Radioisotopes
• N-(1,4,8,11- tetraazacyclotetradecanyl-1,4-phenylenebis(methylene))-2-(aminomethyl)- pyridine
• Pyridines
• Radiopharmaceuticals
• Receptors, CXCR4

Topics

• Animals
• Brain Neoplasms (diagnostic imaging)
• Cell Line, Tumor
• Colonic Neoplasms (diagnostic imaging)
• Copper Radioisotopes
• Female
• Flow Cytometry
• HT29 Cells
• Humans
• Immunohistochemistry
• Mice
• Mice, Inbred NOD
• Neoplasm Transplantation (diagnostic imaging)
• Positron-Emission Tomography
• Pyridines (chemical synthesis, chemistry)
• Radioligand Assay
• Radiopharmaceuticals (chemical synthesis, chemistry)
• Receptors, CXCR4 (biosynthesis)
• Solubility
• Tissue Distribution
• Whole-Body Counting