In Vivo Stability Improvement of Astatobenzene Derivatives by Introducing Neighboring Substituents.

At is a promising radiohalogen for targeted α therapy. However, some astatinated compounds undergo deastatination in vivo, leading to unintended astatine accumulation in nontarget tissues. Recently, a group reported that the in vivo stability of an astato group on an alkyl group could be improved by placing specific substituents around the astato group.

In vivo-stable bis-iminobiotin for targeted radionuclide delivery with the mutant streptavidin.

Targeted delivery of radionuclides to tumors is significant in theranostics applications for precision medicine. Pre-targeting, in which a tumor-targeting vehicle and a radionuclide-loaded effector small molecule are administered separately, holds promise since it can reduce unnecessary internal radiation exposure of healthy cells and can minimize radiation decay. The success of the pre-targeting delivery requires an in vivo-stable tumor-targeting vehicle selectively binding to tumor antigens and an in vivo-stable small molecule effector selectively binding to the vehicle accumulated on the tumor.

Optimizing the pharmacokinetics of an At-labeled RGD peptide with an albumin-binding moiety via the administration of an albumin-binding inhibitor.

Purpose: A probe for targeted alpha therapy (TAT) using the RGD peptide (Ga-DOTA-K([At]APBA)-c(RGDfK) ([At]1)) with albumin-binding moiety (ABM) was recently developed. [At]1 highly accumulated in tumors and significantly inhibited tumor growth in U-87 MG tumor-bearing mice. However, high [At]1 retention in blood may cause critical adverse events, such as hematotoxicity.

Astatine-211-labeled aza-vesamicol derivatives as sigma receptor ligands for targeted alpha therapy.

Introduction: As sigma receptors are abundantly expressed on different types of cancer cells, several radiolabeled sigma receptor ligands have been developed for cancer imaging and therapy. Previously, we synthesized and evaluated radioiodinated aza-vesamicol derivatives, [I]pICNV, [I]mICN5V, and [I]mICN5V. They accumulated in tumors, and [I]mICN5V and [I]mICN5V showed higher tumor to non-target tissue ratios than [I]pICNV.