Abstract
In order to develop a possible C-X-C chemokine receptor type 4 (CXCR4) imaging agent for oncological scintigraphy, [67Ga]-labeled 1,1′-[1,4-Phenylene-bis(methylene)]bis(1,4,8,11-tetraazacyclotetradecane) ([67Ga]-AMD3100) was prepared by using [67Ga]GaCl3 and AMD-3100 for 2 h at 50 °C (radiochemical purity: >95% ITLC, >99% HPLC, specific activity: 1800–2000 TBq/mmol) in acetate buffer. The stability of the complex was checked in the presence of human serum (37 °C) and in the final formulation for four days. The biodistribution of the labeled compound in the vital organs of wild type Sprague-Dawley rats was determined and compared with that of the free Ga3+ cation up to 48 h. Considering the spleen as the target organ, the best target:non target ratios were obtained 48 h post-injection (spleen:blood ratio; 14.5 and spleen:muscle ratio; 88.4). Initial SPECT images and biodistribution results in the wild type rats matched each other and demonstrated rapid washout of the tracer from the urinary tract. SPECT images in human breast carcinoma-bearing mice demonstrated a detectable tumor uptake in 48 h post-injection.
Highlights
The chemokine receptor subtype CXCR4 is an attractive target for cancer diagnosis and treatment as it is overexpressed in more than 70% of human solid tumors, including mammary cancer, prostate cancer, B-cell lymphoma, neuroblastoma, melanoma, cervical adenocarcinoma, and glioma [1]
Recent studies confirmed the necessity of CXCR4 in breast cancer metastasis [3] and imaging studies demonstrated that CXCR4 is required to initiate the proliferation and/or promote survival of breast cancer cells in vivo and suggest that CXCR4 inhibitors, such as; 1,1′-[1,4-Phenylenebis(methylene)]bis(1,4,8,11-tetraazacyclotetradecane)
Previous studies have demonstrated that metals bound to the cyclam core increase the affinity of AMD3100 to the CXCR4 receptor, for instance, a copper complex affinity is increased by 6-fold [5]
Summary
JALILIAN * 3, Yousef FAZAELI 3, Behrouz ALIREZAPOOR 3, Mehraban POULADI 3, Davoud BEIKI 1,2, Stephan MAUS 4, Ali KHALAJ 2. Published: Accepted: September 12th 2013 September 12th 2013 doi:10.3797/scipharm.1305-18. © Aghanejad et al.; licensee Österreichische Apotheker-Verlagsgesellschaft m.
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