Imaging the norepinephrine transporter in neuroblastoma: A comparison of [18F]-MFBG and 123I-MIBG Journal Article
| Authors: | Zhang, H.; Huang, R.; Cheung, N. K. V.; Guo, H.; Zanzonico, P. B.; Thaler, H. T.; Lewis, J. S.; Blasberg, R. G. |
| Article Title: | Imaging the norepinephrine transporter in neuroblastoma: A comparison of [18F]-MFBG and 123I-MIBG |
| Abstract: | 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, 123I/131I-MIBG has several clinical limitations for diagnostic imaging. In the current studies, we evaluated meta-[18F]-fluorobenzylguanidine ([18F]-MFBG) and compared it with 123I-MIBG for imaging NET-expressing neuroblastomas. Experimental Design: NET expression levels in neuroblastoma cell lines were determined by Western blot and 123I-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 [18F]-MFBG in cells was specific and proportional to the expression level of NET. Although [18F]-MFBG had a 3-fold lower affinity for NET and an approximately 2-fold lower cell uptake in vitro compared with that of 123I-MIBG, the in vivo imaging and tissue radioactivity concentration measurements demonstrated higher [18F]-MFBG xenograft uptake and tumor-to-normal organ ratios at 1 and 4 hours after injection. A comparison of 4 hours [18F]-MFBG PET (positron emission tomography) imaging with 24 hours 123I-MIBG SPECT (single-photon emission computed tomography) imaging showed an approximately 3-fold higher tumor uptake of [18F]-MFBG, but slightly lower tumor-to-background ratios in mice. Conclusions: [18F]-MFBG is a promising radiopharmaceutical for specifically imaging NET-expressing neuroblastomas, with fast pharmacokinetics and whole-body clearance. [18F]-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 131I/123I-MIBG. © 2014 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 20 |
| Issue: | 8 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2014-04-15 |
| Start Page: | 2182 |
| End Page: | 2191 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-13-1153 |
| PROVIDER: | scopus |
| PUBMED: | 24573553 |
| PMCID: | PMC4072734 |
| DOI/URL: | |
| Notes: | Clin. Cancer Res. -- Export Date: 2 June 2014 -- CODEN: CCREF -- Source: Scopus |
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