Imaging CXCR4 expression in human cancer xenografts: evaluation of monocyclam 64Cu-AMD3465
Ravindra A De Silva1, Kevin Peyre, Mrudula Pullambhatla
1Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland 21231, USA.
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.
Insights
This study introduces (64)Cu-AMD3465, a novel imaging agent targeting chemokine receptor 4 (CXCR4). It effectively detects CXCR4-positive tumors, showing high selectivity for potential use in cancer diagnosis and monitoring.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Chemokine receptor 4 (CXCR4) is overexpressed in various cancers and metastases.
- CXCR4 is a promising target for molecular imaging, diagnosis, staging, and therapeutic monitoring of cancer.
Purpose of the Study:
- To evaluate the positron-emitting monocyclam analog, (64)Cu-AMD3465, as a CXCR4-based imaging agent.
- To assess the efficacy of (64)Cu-AMD3465 in detecting subcutaneous U87 brain tumors and HT-29 colon tumors.
Main Methods:
- Dynamic and whole-body PET/CT imaging were employed in U87 brain tumor and HT-29 colon tumor models.
- Ex vivo biodistribution studies supported the PET/CT findings.
- Tumor uptake and tumor-to-muscle ratios were quantified after radiotracer injection.
Main Results:
- Specific accumulation of radioactivity was observed in U87-stb-CXCR4 tumors and HT-29 colon tumors.
- Maximum injected dose per gram in U87-stb-CXCR4 tumors reached 102.70 ± 20.80 at 60 min.
- Maximum tumor-to-muscle ratios reached 362.56 ± 153.51 at 90 min, indicating high target selectivity.
- AMD3465 treatment inhibited radioactivity uptake in tumors, confirming CXCR4-dependent detection.
Conclusions:
- (64)Cu-AMD3465 effectively detects lesions in a CXCR4-dependent manner.
- The agent exhibits high target selectivity, making it suitable for molecular imaging.
- (64)Cu-AMD3465 serves as a potential scaffold for developing clinically translatable imaging agents.
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