Norepinephrine transporter and vesicular monoamine transporter 2 tumor expression as a predictor of response to 131 I-MIBG in patients with relapsed/refractory neuroblastoma

• Published in: Pediatric blood & cancer 2024-01, Vol.71 (1), p.e30743-e30743
• Main Authors: Batra, Vandana, Gikandi, Ajami, Pawel, Bruce, Martinez, Daniel, Granger, M Meaghan, Marachelian, Araz, Park, Julie R, Maris, John M, Vo, Kieuhoa T, Matthay, Katherine K, DuBois, Steven G
• Format: Article
• Language: English
• Subjects: 3-Iodobenzylguanidine - therapeutic use; Chronic Disease; Humans; N-Myc Proto-Oncogene Protein; Neoplasm Recurrence, Local - drug therapy; Neuroblastoma - drug therapy; Norepinephrine Plasma Membrane Transport Proteins - metabolism; Radiopharmaceuticals; Vesicular Monoamine Transport Proteins - metabolism
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.30743

Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to I-MIBG therapy in patients with neuroblastoma. Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with I-MIBG. A composite protein expression H-score was determined by multiplying a semi-quantitative intensity value (0-3+) by the percentage of tumor cells expressing the protein. Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for