Journal of labelled compounds & radiopharmaceuticals最新文献

N-((1R,4R)-4-(3-Chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (ARV-110) is a proteolysis-targeting chimera (PROTAC) designed against the androgen receptor (AR), which shows great potential for treating AR-dependent diseases, such as prostate cancer. To support preclinical safety evaluations as well as studies of drug metabolism and pharmacokinetics, two versions of carbon-14-labeled ARV-110 were synthesized: N-((1R,4R)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-[1,3-¹⁴C2]dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (¹⁴C-ARV-110-a) and N-((1R,4R)-4-(3-chloro-4-[cyano-¹⁴C]cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (¹⁴C-ARV-110-b). The synthesis of ¹⁴C-ARV-110-a was initiated from 1,2-dibromo-4,5-difluorobenzene and zinc cyanide-¹⁴C (Zn(¹⁴CN)₂), while ¹⁴C-ARV-110-b was prepared from 2-chloro-4-fluoro[cyano-¹⁴C]benzonitrile.

Deucravacitinib (BMS-986165) is a small molecule allosteric inhibitor of tyrosine kinase 2 (TYK2) currently approved for the treatment of moderate to severe plaque psoriasis. Tyrosine kinase 2 (TYK2) is a member of the Janus (JAK) family of non-receptor kinases that modulate the production of inflammatory cytokines. The synthesis of ¹⁴C-radiolabeled and stable-isotope labeled variants of deucravacitinib is described in this publication.

Fluorine-18 labeling of peptides and proteins is typically performed by an indirect labeling method. In this labeling approach, a labeled prosthetic group is prepared first and then conjugated to the proteins and peptides of interest. 6-[¹⁸F]fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester is a useful prosthetic group for indirect labeling. We have recently developed an efficient radiolabeling method, “fluorination on Sep-Pak,” that enables the preparation of this prosthetic group with high radiochemical yield and purity in under 10 min. A variety of biomolecules have been radiolabeled using this prosthetic group. The radiolabeling procedure was either manual or semiautomated. However, a fully automated synthesis method is essential for successful clinical translation. Therefore, we developed a fully automated reproducible radiolabeling method to prepare fluorine-18–labeled albumin using the Trasis AllinOne module. The procedure was completed in 50 min. The overall radiochemical yield was 25%–36% (decay-corrected, n = 6) using 1 mg of albumin with a radiochemical purity > 98%.

Angiogenesis, particularly driven by the overexpression of vascular endothelial growth factor (VEGF), plays a crucial role in the growth and metastasis of tumors, making VEGF a significant target in the diagnosis and therapy of non-small cell lung cancer (NSCLC). In this work, the potential of ^99mTc-labeled ranibizumab was investigated for the non-invasive diagnosis of NSCLC. To that end, ranibizumab (RNB), a VEGF-neutralizing antibody, was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza1,4,7,10-tetra(2-carbamoylmethyl) cyclododecane (TCMC) followed by labeling with technetium-99m (^99mTc) using different reaction parameters. The ^99mTc-TCMC-RNB was characterized in terms of the percent radiochemical purity (% RCP) up to 6 h, in vitro stability in serum up to 16 h, internalization kinetics in A549 cells, and biodistribution using the NSCLC Sprague Dawley rat model. The ^99mTc-labeled TCMC-RNB exhibited 98.3 ± 0.2% RCP in normal saline, stability in rat serum with an overall decay of 32.10% within 18 h, and specific binding to A549 NSCLC cells. Biodistribution studies showed significant tumor uptake. These findings suggest that ^99mTc-labeled TCMC-RNB holds promise as a specific imaging agent for the diagnosis and monitoring of VEGF-related malignancies, particularly in NSCLC.