Journal
CLINICAL CANCER RESEARCH
Volume 20, Issue 8, Pages 2182-2191Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-13-1153
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Funding
- NIH [P50-CA84638]
- U.S. Department of Energy Award [DE-SC0002456]
- NIH Center grant [P30-CA08748]
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Purpose: The norepinephrine transporter (NET) is a critical regulator of catecholamine uptake in normal physiology and is expressed in neuroendocrine tumors like neuroblastoma. Although the norepinephrine analog, meta-iodobenzylguanidine (MIBG), is an established substrate for NET, I-123/I-131-MIBG has several clinical limitations for diagnostic imaging. In the current studies, we evaluated meta-[F-18]-fluorobenzylguanidine ([F-18]-MFBG) and compared it with I-123-MIBG for imaging NET-expressing neuroblastomas. Experimental Design: NET expression levels in neuroblastoma cell lines were determined by Western blot and I-123-MIBG uptake assays. Five neuroblastoma cell lines and two xenografts (SK-N-BE(2) C and LAN1) expressing different levels of NET were used for comparative in vitro and in vivo uptake studies. Results: The uptake of [F-18]-MFBG in cells was specific and proportional to the expression level of NET. Although [F-18]-MFBG had a 3-fold lower affinity for NET and an approximately 2-fold lower cell uptake in vitro compared with that of I-123-MIBG, the in vivo imaging and tissue radioactivity concentration measurements demonstrated higher [F-18]-MFBG xenograft uptake and tumor-to-normal organ ratios at 1 and 4 hours after injection. A comparison of 4 hours [F-18]-MFBG PET (positron emission tomography) imaging with 24 hours I-123-MIBG SPECT (single-photon emission computed tomography) imaging showed an approximately 3-fold higher tumor uptake of [F-18]-MFBG, but slightly lower tumor-to-background ratios in mice. Conclusions: [F-18]-MFBG is a promising radiopharmaceutical for specifically imaging NET-expressing neuroblastomas, with fast pharmacokinetics and whole-body clearance. [F-18]-MFBG PET imaging shows higher sensitivity, better detection of small lesions with low NET expression, allows same day scintigraphy with a shorter image acquisition time, and has the potential for lower patient radiation exposure compared with I-131/I-123-MIBG. (C) 2014 AACR.
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