%0 Journal Article
%T Evaluation of Norepinephrine Transporter Expression and Metaiodobenzylguanidine Avidity in Neuroblastoma: A Report from the Children's Oncology Group
%A Steven G. DuBois
%A Ethan Geier
%A Vandana Batra
%A Sook Wah Yee
%A John Neuhaus
%A Mark Segal
%A Daniel Martinez
%A Bruce Pawel
%A Greg Yanik
%A Arlene Naranjo
%A Wendy B. London
%A Susan Kreissman
%A David Baker
%A Edward Attiyeh
%A Michael D. Hogarty
%A John M. Maris
%A Kathleen Giacomini
%A Katherine K. Matthay
%J International Journal of Molecular Imaging
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/250834
%X Purpose. 123I-metaiodobenzylguanidine (MIBG) is used for the diagnostic evaluation of neuroblastoma. We evaluated the relationship between norepinephrine transporter (NET) expression and clinical MIBG uptake. Methods. Quantitative reverse transcription PCR ( ) and immunohistochemistry (IHC; ) were performed for neuroblastoma NET mRNA and protein expression and correlated with MIBG avidity on diagnostic scans. The correlation of NET expression with clinical features was also performed. Results. Median NET mRNA expression level for the 19 MIBG avid patients was 12.9% (range 1.6每73.7%) versus 5.9% (range 0.6每110.0%) for the 8 nonavid patients ( ). Median percent NET protein expression was 50% (range 0每100%) in MIBG avid patients compared to 10% (range 0每80%) in nonavid patients ( ). MYCN amplified tumors had lower NET protein expression compared to nonamplified tumors (10% versus 50%; ). Conclusions. NET protein expression in neuroblastoma correlates with MIBG avidity. MYCN amplified tumors have lower NET protein expression. 1. Introduction Metaiodobenzylguanidine (MIBG) is an agent that is specifically taken up by sympathetic nervous system tissues, including neuroblastoma tumors. 123I-MIBG plays an essential role in the diagnostic evaluation of patients with neuroblastoma [1]. In addition, high-dose 131I-MIBG therapy is an important part of the treatment of patients with relapsed or refractory neuroblastoma [2]. The norepinephrine transporter (NET; encoded by SLC6A2 gene) is thought to be the primary transporter responsible for specific active cellular uptake of MIBG [3]. Several studies have demonstrated that neuroblastoma cell lines that lack NET mRNA expression fail to accumulate MIBG [4每6]. NET mRNA levels appear to correlate in vitro with extent of MIBG uptake [6每8]. Moreover, a range of cells that do not typically accumulate MIBG can be engineered to do so by transfection of the NET gene [9每17]. Additional studies in neuroblastoma and other neuroendocrine tumors have suggested that vesicular monoamine transporters (VMATs) and organic cation transporters (OCTs) may also play a role in mediating uptake of MIBG [18每20]. Approximately 10% of patients with neuroblastoma have tumors that do not accumulate MIBG on the basis of negative diagnostic 123I-MIBG scans [21]. The determinants of MIBG-avidity in clinical neuroblastoma tumors are unknown. One small study utilized RT-PCR to evaluate NET gene expression in 6 neuroblastoma tumors from patients with negative baseline MIBG diagnostic scans [4]. None of these tumors had detectable NET mRNA, while 90% of
%U http://www.hindawi.com/journals/ijmi/2012/250834/