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Meeting ReportOncology-Basic: Basic Science

Evaluation of CXCR4 expression in experimental brain tumor xenografts with [64Cu]AMD3100

Sridhar Nimmagadda, Mrudula Pullambhatla, Gilbert Green, Zaver Bhujwalla and Martin Pomper
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 280;
Sridhar Nimmagadda
1Radiology, Johns Hopkins University, Baltimore, MD
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Mrudula Pullambhatla
1Radiology, Johns Hopkins University, Baltimore, MD
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Gilbert Green
1Radiology, Johns Hopkins University, Baltimore, MD
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Zaver Bhujwalla
1Radiology, Johns Hopkins University, Baltimore, MD
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Martin Pomper
1Radiology, Johns Hopkins University, Baltimore, MD
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Abstract

280

Objectives Chemokine receptor 4 (CXCR4) is expressed in a variety of cancers including breast, brain, ovarian and prostate. CXCR4/CXCL12 interactions are critical for tumor development, growth and metastasis. Here we have developed and evaluated a positron-emitting analog of the CXCR4 inhibitor Plerixafor, [64 Cu]AMD3100, in brain tumor xenografts stably expressing CXCR4.

Methods AMD3100 was radiolabeled by incubating with [64Cu]Cu(OAc)2 and purified by high-performance liquid chromatography. The human Glioma cell line U87 stably expressing CXCR4 (U87-stb-CXCR4) and parental U87 cell lines were used to generate subcutaneous xenografts. After IV injection of 10 MBq of [64Cu]AMD3100, dynamic PET imaging was acquired for 60 min followed by whole body images at 90 min. For biodistribution studies mice receiving 740 kBq of [64Cu]AMD3100 were sacrificed and tissues were harvested at selected time intervals. The specificity of [64Cu]AMD3100 was confirmed by blocking studies and receptor expression was quantified by flow cytometry. A minimum of three animals was used for all studies.

Results [64Cu]AMD3100 was obtained in 40-60 % yield, with 134±61 GBq/μmol specific activity and > 95% purity. Imaging and biodistribution studies showed specific accumulation of [64Cu]AMD3100 in U87-stb-CXCR4 tumors with %ID/g reaching 30 ± 2.18. The U87-stb-CXCR4 to U87 tumor ratios reached a maximum of 6.16 ± 1.37 at 90 min. The tumor-to-muscle ratios at 90 min were 47.36 ± 6.93 and 13.39 ± 4.20 for U87-stb-CXCR4 and U87, respectively. Blocking studies demonstrated greater than 80% reduction of radioactivity signal in both tumors.

Conclusions These data demonstrate the feasibility of imaging variable CXCR4 expression with [64Cu]AMD3100.

Research Support U24 CA92871, P50CA103175, American Brain Tumor Associatio

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Journal of Nuclear Medicine
Vol. 51, Issue supplement 2
May 2010
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Evaluation of CXCR4 expression in experimental brain tumor xenografts with [64Cu]AMD3100
Sridhar Nimmagadda, Mrudula Pullambhatla, Gilbert Green, Zaver Bhujwalla, Martin Pomper
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 280;

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Evaluation of CXCR4 expression in experimental brain tumor xenografts with [64Cu]AMD3100
Sridhar Nimmagadda, Mrudula Pullambhatla, Gilbert Green, Zaver Bhujwalla, Martin Pomper
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 280;
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