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Imaging the Norepinephrine Transporter in Neuroblastoma: A Comparison of [18F]-MFBG and 123I-MIBG
- Source :
- Clinical Cancer Research. 20:2182-2191
- Publication Year :
- 2014
- Publisher :
- American Association for Cancer Research (AACR), 2014.
-
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. Clin Cancer Res; 20(8); 2182–91. ©2014 AACR.
- Subjects :
- Diagnostic Imaging
Cancer Research
Immunoblotting
Transplantation, Heterologous
Scintigraphy
Guanidines
Article
Mice
Neuroblastoma
In vivo
Cell Line, Tumor
medicine
Animals
Humans
Tissue Distribution
Catecholamine uptake
Tomography, Emission-Computed, Single-Photon
Norepinephrine Plasma Membrane Transport Proteins
medicine.diagnostic_test
biology
business.industry
Reproducibility of Results
medicine.disease
Immunohistochemistry
Fluorobenzenes
Transplantation
3-Iodobenzylguanidine
Oncology
Norepinephrine transporter
Positron emission tomography
Positron-Emission Tomography
biology.protein
Cancer research
Radiopharmaceuticals
Nuclear medicine
business
Preclinical imaging
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....e6b355d056c016732043c4639366bfa9