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⁶⁴Cu-AMD3100: A potential radiotracer for in vivo visualization of the chemokine receptor CXCR4

¹ Radioimmunotherapy, City of Hope, Duarte, California

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Objectives: The CXCR4 receptor is highly expressed on certain types of white blood cells (WBC) and hematopoietic stem cells (HSC), providing a homing mechanism for such cells to tissues and organs that excrete the chemokine CXCL12. CXCR4/CXCL12 also has a central role in tumor metastasis. We labeled the CXCR4 antagonist AMD3100 (mol wt 794) with ⁶⁴Cu and used it for in vivo imaging and biodistribution measurements in mice.

Methods: AMD3100 in ammonium acetate was added to ⁶⁴Cu copper chloride and incubated at 37^oC for 30 min, after which non-radioactive copper (2:1 molar ratio) was added. Reverse-phase chromatography (C18 column) demonstrated a single radioactive peak eluting at the same time as [Cu₂]AMD3100. Immune-competent C57Bl mice were injected i.v. with either 0.06 ("low-dose"; n=2) or 0.46 ("high-dose"; n=2) µg/g of ⁶⁴Cu-AMD3100 (130-180 kBq/g). Scans were acquired at 0.5, 1, 2 and 4 h using an R4 microPET^TM (Siemens/CTMI), after which the mice were euthanized and biodistribution of ⁶⁴Cu was measured by direct assay.

Results: Radiolabel was rapidly cleared into urine (>50% by 4 h) and liver (35-41% injected dose/g between 1 and 4 h in the low-dose group). Uptake was highest in tissues and organs known to constitutively express CXCL12 and/or harbor large concentrations of WBC or HSC, namely liver, bone, spleen, and lung. Uptake in each of these was reduced in the high-dose relative to the low-dose group, indicating a saturable uptake mechanism. Percentage of whole blood ⁶⁴Cu in the cellular fraction at 4 h was also lower in the high-dose compared with the low-dose group (33±13% compared with 52±1%).

Conclusions: The bicyclam AMD3100, a natural chelating agent, is readily labeled with ⁶⁴Cu. The biodistribution in immune competent mice was consistent with specific binding of the radiotracer to CXCR4.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bading, J. Articles by Shively, J. PubMed Articles by Bading, J. Articles by Shively, J.