title: Radiolabeling and initial biological evaluation of [18F]KBM-1 for imaging RAR-α receptors in neuroblastoma.
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 treated13-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 [18F]KBM-1, a novel RAR-α agonist. The radiochemical synthesis of [18F]KBM-1 was carried out through KHF2assisted substitution of [18F]-from aryl-substituted pinacolatoesters-based retinoid precursor. In vitro cell uptake assay in human neuroblastoma cell line showed that the uptake of [18F]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 5min to 60min post radiotracer injection and the uptake ratios for target to non-target (tumor: muscle) increased 2.2-fold to 3.7-fold from 30min to 60min post injection. Tumor uptake in subset of 30min blocking group was 1.7-fold lower than unblocked. These results demonstrate the potential utility of [18F]KBM-1 as a RAR-α imaging agent.
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston Salem, NC, USA. Electronic address: ksolinga@wakehealth.edu.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Solingapuram Sai
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston Salem, NC, USA. Electronic address: Bhaskar.das@va.gov.
authors.forename: Bhaskar C
authors.initials: BC
authors.lastname: Das
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Anirudh
authors.initials: A
authors.lastname: Sattiraju
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Frankis G
authors.initials: FG
authors.lastname: Almaguel
authors.affiliation: Internal Medicine, Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston Salem, NC, USA. Electronic address: amintz@wakehealth.edu.
authors.forename: Akiva
authors.initials: A
authors.lastname: Mintz
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001896:Boron Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009447:Neuroblastoma / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha / Q000819:agonists / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D001578:Benzopyrans; D001896:Boron Compounds; D005462:Fluorine Radioisotopes; D000072482:Retinoic Acid Receptor alpha
keywords: All-trans retinoic acid (ATRA); Biodistribution; Neuroblastoma; Retinoic acid receptor alpha (RAR-α)