使用 64Cu-AMD3100 对表达人趋化因子受体 CXCR4 的肿瘤进行正电子发射断层成像。
Positron emission tomography imaging of tumors expressing the human chemokine receptor CXCR4 in mice with the use of 64Cu-AMD3100.
机构信息
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, 10 Center Drive, Room 11N111, Bethesda, MD 20892, USA.
出版信息
Mol Imaging Biol. 2012 Feb;14(1):106-14. doi: 10.1007/s11307-010-0466-y.
PURPOSE
Expression of CXCR4 in cancers has been correlated with poor prognosis and increased metastasis. Quantifying CXCR4 expression non-invasively might aid in prognostication and monitoring therapy. We evaluated a radiolabeled antagonist of CXCR4, ⁶⁴Cu-AMD3100, as a positron-emitting imaging agent.
PROCEDURES
CXCR4-transfected or non-transfected cell lines were injected into mice to form xenografts. Accumulation of ⁶⁴Cu-AMD3100 in tumors was analyzed by small-animal PET and biodistribution assays.
RESULTS
⁶⁴Cu-AMD3100 accumulated in CXCR4-expressing, but not CXCR4-negative, tumors. For CXCR4-expressing tumors, tumor-to-blood and tumor-to-muscle ratios were 23-41 and 50-59, respectively, depending on tumor type. Excess of unlabeled Cu-AMD3100 or AMD3100 significantly reduced ⁶⁴Cu-AMD3100 accumulation in CXCR4-expressing tumors. Human-absorbed dose calculations predicted a dose limit of 444 MBq.
CONCLUSIONS
CXCR4 can be imaged in tumors using ⁶⁴Cu-AMD3100. Dosimetry studies suggest that imaging in humans is feasible. We conclude that ⁶⁴Cu-AMD3100 should be investigated as a potential agent for imaging and quantifying CXCR4 in tumors.
目的
CXCR4 在癌症中的表达与预后不良和转移增加有关。非侵入性地定量 CXCR4 的表达可能有助于预后判断和监测治疗。我们评估了一种 CXCR4 的放射性配体拮抗剂 ⁶⁴Cu-AMD3100，作为正电子发射成像剂。
方法
将 CXCR4 转染或未转染的细胞系注射到小鼠中形成异种移植物。通过小动物 PET 和生物分布测定分析 ⁶⁴Cu-AMD3100 在肿瘤中的积累。
结果
⁶⁴Cu-AMD3100 在表达 CXCR4 的肿瘤中积累，但在不表达 CXCR4 的肿瘤中不积累。对于表达 CXCR4 的肿瘤，肿瘤与血液和肿瘤与肌肉的比值分别为 23-41 和 50-59，具体取决于肿瘤类型。过量的未标记的 Cu-AMD3100 或 AMD3100 显著降低了表达 CXCR4 的肿瘤中 ⁶⁴Cu-AMD3100 的积累。人体吸收剂量计算预测剂量限制为 444 MBq。
结论
可以使用 ⁶⁴Cu-AMD3100 在肿瘤中成像 CXCR4。剂量学研究表明，在人类中进行成像可行。我们得出结论， ⁶⁴Cu-AMD3100 应作为成像和定量肿瘤中 CXCR4 的潜在药物进行研究。
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