Radiosynthesis of microtubule-targeted theranostic methyl N-[5-(3'-radiohalobenzoyl)-1H-benzimidazol-2-yl]carbamates
Kortylewicz, ZP; Baranowska-Kortylewicz, J
| HERO ID | 5410578 |
|---|---|
| In Press | No |
| Year | 2018 |
| Title | Radiosynthesis of microtubule-targeted theranostic methyl N-[5-(3'-radiohalobenzoyl)-1H-benzimidazol-2-yl]carbamates |
| Authors | Kortylewicz, ZP; Baranowska-Kortylewicz, J |
| Journal | Journal of Labelled Compounds and Radiopharmaceuticals |
| Volume | 61 |
| Issue | 10 |
| Page Numbers | 749-756 |
| 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. 125 I- and 131 I-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 125 I-4 and 131 I-4. Radioiododestannylation of 3'-trimethylstannane 3 proceeded with ease at room temperature in the presence of H2 O2 as the oxidant and produced no-carrier-added 125 I-4 and 131 I-4 in high isolated yields, on average 85%. The radiohalodestannylation protocol is universal and can be applied to other radiohalides including 124 I to produce 124 I-4, a positron emission tomography agent, and 211 At to produce 211 At-4, an α-particle emitting radiotherapeutic. |
| Doi | 10.1002/jlcr.3631 |
| Pmid | 29707803 |
| Wosid | WOS:000441694900002 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85051431141&doi=10.1002%2fjlcr.3631&partnerID=40&md5=34ffd2cc527f20e2854dda80c71b47ca |
| Is Public | Yes |
| Language Text | English |
| Keyword | benzimidazole; imaging; microtubules; molecular radiotherapy; radiohalides; theranostic; carbamic acid derivative; hydrogen peroxide; methyl n [5 (3' iodobenzoyl) 1h benzimidazol 2 yl]carbamate; methyl n [5 (3' iodobenzoyl) 1h benzimidazol 2 yl]carbamate i 125; methyl n [5 (3' iodobenzoyl) 1h benzimidazol 2 yl]carbamate i 131; methyl n [5 (3' trimethylstannylbenzoyl) 1h benzimidazol 2 yl]carbamate; radiopharmaceutical agent; unclassified drug; Article; drug synthesis; high performance liquid chromatography; human; radioiodination; room temperature |