Radiosynthesis of microtubule-targeted theranostic methyl N-[5-(3’-radiohalobenzoyl)-1H-benzimidazol-2-yl]carbamates

Zbigniew P. Kortylewicz, Janina Baranowska-Kortylewicz

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Microtubules are a target for a broad spectrum of drugs used as chemotherapeutics to treat hematological malignancies and solid tumors. Most of these drugs have significant dose-limiting toxicities including peripheral neuropathies that can be debilitating and permanent. In an ongoing effort to develop safer and more effective drugs, benzimidazole-based compounds are being developed as replacement for vincristine and similar agents. In this report, we describe radiosyntheses of novel microtubule-targeting methyl N-[5-(3’-radiohalobenzoyl)-1H-benzimidazol-2-yl]carbamates 4 that are intended as potential imaging agents and molecular radiotherapeutics. 125I- and 131I-radiolabeled derivatives were prepared either by direct radioiodination of methyl N-(6-benzoyl-1H-benzimidazol-2-yl)carbamate 1 or radioiododestannylation of the corresponding stannane precursor 3. The direct radioiodination was conducted in a solution of 1 in triflic acid and produced after ~1 hour at elevated temperatures and HPLC purification on average 62% of the no-carrier added products 125I-4 and 131I-4. Radioiododestannylation of 3’-trimethylstannane 3 proceeded with ease at room temperature in the presence of H2O2 as the oxidant and produced no-carrier-added 125I-4 and 131I-4 in high isolated yields, on average 85%. The radiohalodestannylation protocol is universal and can be applied to other radiohalides including 124I to produce 124I-4, a positron emission tomography agent, and 211At to produce 211At-4, an α-particle emitting radiotherapeutic.

Original languageEnglish (US)
Pages (from-to)749-756
Number of pages8
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume61
Issue number10
DOIs
StatePublished - Aug 2018

Fingerprint

Carbamates
Microtubules
Pharmaceutical Preparations
Positron emission tomography
Temperature
Molecular Imaging
Vincristine
Peripheral Nervous System Diseases
Hematologic Neoplasms
Oxidants
Positron-Emission Tomography
Purification
Toxicity
Tumors
High Pressure Liquid Chromatography
Derivatives
Imaging techniques
Theranostic Nanomedicine
Neoplasms

Keywords

  • benzimidazole
  • imaging
  • microtubules
  • molecular radiotherapy
  • radiohalides
  • theranostic

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Cite this

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abstract = "Microtubules are a target for a broad spectrum of drugs used as chemotherapeutics to treat hematological malignancies and solid tumors. Most of these drugs have significant dose-limiting toxicities including peripheral neuropathies that can be debilitating and permanent. In an ongoing effort to develop safer and more effective drugs, benzimidazole-based compounds are being developed as replacement for vincristine and similar agents. In this report, we describe radiosyntheses of novel microtubule-targeting methyl N-[5-(3’-radiohalobenzoyl)-1H-benzimidazol-2-yl]carbamates 4 that are intended as potential imaging agents and molecular radiotherapeutics. 125I- and 131I-radiolabeled derivatives were prepared either by direct radioiodination of methyl N-(6-benzoyl-1H-benzimidazol-2-yl)carbamate 1 or radioiododestannylation of the corresponding stannane precursor 3. The direct radioiodination was conducted in a solution of 1 in triflic acid and produced after ~1 hour at elevated temperatures and HPLC purification on average 62{\%} of the no-carrier added products 125I-4 and 131I-4. Radioiododestannylation of 3’-trimethylstannane 3 proceeded with ease at room temperature in the presence of H2O2 as the oxidant and produced no-carrier-added 125I-4 and 131I-4 in high isolated yields, on average 85{\%}. The radiohalodestannylation protocol is universal and can be applied to other radiohalides including 124I to produce 124I-4, a positron emission tomography agent, and 211At to produce 211At-4, an α-particle emitting radiotherapeutic.",
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