Radiolabeling and initial biological evaluation of [18F]KBM-1 for imaging RAR-α receptors in neuroblastoma. Issue 6 (15th March 2017)

• Record Type: Journal Article
• Authors: Solingapuram Sai, Kiran Kumar; Das, Bhaskar C.; Sattiraju, Anirudh; Almaguel, Frankis G.; Craft, Suzanne; Mintz, Akiva
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 6(2017)
• Page Start: 1425
• Page End: 1427
• Publication Date: 2017-03-15
• Subjects: Retinoic acid receptor alpha (RAR-α) -- All-trans retinoic acid (ATRA) -- Biodistribution -- Neuroblastoma; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.01.093
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Ratio of target (tumor): nontarget (muscle) at 5 min, 30 min and 60 min post injection of [ 18 F]KBM-1 in mice bearing neuroblastoma tumor (n = 4). Abstract: Retinoic acid receptor alpha (RAR-α) plays a significant role in a number of diseases, including neuroblastoma. Children diagnosed with high-risk neuroblastoma are treated 13-cis-retinoic acid, which reduces risk of cancer recurrence. Neuroblastoma cell death is mediated via RAR-α, and expression of RAR-α is upregulated after treatment. A molecular imaging probe that binds RAR-α will help clinicians to diagnose and stratify risk for patients with neuroblastoma, who could benefit from retinoid-based therapy. In this study, we report the radiolabeling, and initial in vivo evaluation of [ 18 F]KBM-1, a novel RAR-α agonist. The radiochemical synthesis of [ 18 F]KBM-1 was carried out through KHF2 assisted substitution of [ 18 F] − from aryl-substituted pinacolatoesters-based retinoid precursor. In vitro cell uptake assay in human neuroblastoma cell line showed that the uptake of [ 18 F]KBM-1 was significantly inhibited by all three blocking agents (KBM-1, ATRA, BD4 ) at all the selected incubation times. Standard biodistribution in mice bearing neuroblastoma tumors demonstrated increased tumor uptake from 5 min to 60 min post radiotracer injection and the uptake ratios for target to non-target (tumor: muscle) increased 2.2-fold to 3.7-fold from 30 min to 60 min post injection. Tumor uptake in subset of 30 min blocking group was 1.7-fold lower than unblocked. These results demonstrate the potential utility of [ 18 F]KBM-1 as a RAR-α imaging agent.