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Radiolabeling and initial biological evaluation of [ 18 F]KBM-1 for imaging RAR-α receptors in neuroblastoma.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Mar 15; Vol. 27 (6), pp. 1425-1427. Date of Electronic Publication: 2017 Feb 01. - Publication Year :
- 2017
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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 [ <superscript>18</superscript> F]KBM-1, a novel RAR-α agonist. The radiochemical synthesis of [ <superscript>18</superscript> F]KBM-1 was carried out through KHF <subscript>2</subscript> assisted substitution of [ <superscript>18</superscript> F] <superscript>-</superscript> from aryl-substituted pinacolatoesters-based retinoid precursor. In vitro cell uptake assay in human neuroblastoma cell line showed that the uptake of [ <superscript>18</superscript> 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 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 [ <superscript>18</superscript> F]KBM-1 as a RAR-α imaging agent.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Benzopyrans chemistry
Benzopyrans pharmacokinetics
Boron Compounds chemistry
Boron Compounds pharmacokinetics
Cell Line, Tumor
Drug Screening Assays, Antitumor
Heterografts
Humans
Kidney metabolism
Liver metabolism
Mice
Mice, Inbred BALB C
Retinoic Acid Receptor alpha agonists
Tissue Distribution
Benzopyrans pharmacology
Boron Compounds pharmacology
Fluorine Radioisotopes metabolism
Neuroblastoma metabolism
Retinoic Acid Receptor alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 27
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 28216044
- Full Text :
- https://doi.org/10.1016/j.bmcl.2017.01.093