Light-Driven Radiochemistry with Fluorine-18, Carbon-11 and Zirconium-89.

This review discusses recent advances in light-driven radiochemistry for three key isotopes: fluorine-18, carbon-11, and zirconium-89, and their applications in positron emission tomography (PET). In the case of fluorine-18, the predominant approach involves the use of cyclotron-produced [F]fluoride or reagents derived thereof. Light serves to activate either the substrate or the fluorine-18 labeled reagent.

GTP1 metabolic stability assessment: A study of the tau PET tracer [F]GTP1.

Tau PET imaging using the tau specific PET tracer [F]GTP1 has been and is part of therapeutic trials in Alzheimer's disease to monitor the accumulation of tau aggregates in the brain. Herein, we examined the metabolic processes of GTP1 and assessed the influence of smoking on its metabolism through in vitro assays. The tracer metabolic profile was assessed by incubating GTP1 with human liver microsomes (HLM) and human hepatocytes.

Development of an F-labeled anti-human CD8 VHH for same-day immunoPET imaging.

Purpose: Cancer immunotherapies (CITs) have revolutionized the treatment of certain cancers, but many patients fail to respond or relapse from current therapies, prompting the need for new CIT agents. CD8 T cells play a central role in the activity of many CITs, and thus, the rapid imaging of CD8 cells could provide a critical biomarker for new CIT agents. However, existing Zr-labeled CD8 PET imaging reagents exhibit a long circulatory half-life and high radiation burden that limit potential applications such as same-day and longitudinal imaging.

Preclinical development of ZED8, an Zr immuno-PET reagent for monitoring tumor CD8 status in patients undergoing cancer immunotherapy.

Background: ZED8 is a novel monovalent antibody labeled with zirconium-89 for the molecular imaging of CD8. This work describes nonclinical studies performed in part to provide rationale for and to inform expectations in the early clinical development of ZED8, such as in the studies outlined in clinical trial registry NCT04029181 [1].

Methods: Surface plasmon resonance, X-ray crystallography, and flow cytometry were used to characterize the ZED8-CD8 binding interaction, its specificity, and its impact on T cell function.