Preclinical biodistribution and dosimetry and human biodistribution comparing F-rhPSMA-7 and single isomer F-rhPSMA-7.3.

Background: Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands such as F-rhPSMA-7 are a new class of theranostic agents in clinical development for prostate cancer. We compared preclinical dosimetry and human biodistribution of F-rhPSMA-7 with that of single diastereoisomer form, F-rhPSMA-7.3.

Comparative Preclinical Biodistribution, Dosimetry, and Endoradiotherapy in Metastatic Castration-Resistant Prostate Cancer Using F/Lu-rhPSMA-7.3 and Lu-PSMA I&T.

Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are applicable as radiochemical twins for both diagnostic PET imaging and endoradiotherapy. On the basis of preliminary data as a diagnostic ligand, the isomer rhPSMA-7.3 is a promising candidate for potential endoradiotherapy.

Key Features Relevant to Select Antigens and TCR From the MHC-Mismatched Repertoire to Treat Cancer.

Adoptive transfer of T cells transgenic for tumor-reactive T-cell receptors (TCR) is an attractive immunotherapeutic approach. However, clinical translation is so far limited due to challenges in the identification of suitable target antigens as well as TCRs that are concurrent safe and efficient. Definition of key characteristics relevant for effective and specific tumor rejection is essential to improve current TCR-based adoptive T-cell immunotherapies.

T-cell functionality testing is highly relevant to developing novel immuno-tracers monitoring T cells in the context of immunotherapies and revealed CD7 as an attractive target.

Cancer immunotherapy has proven high efficacy in treating diverse cancer entities by immune checkpoint modulation and adoptive T-cell transfer. However, patterns of treatment response differ substantially from conventional therapies, and reliable surrogate markers are missing for early detection of responders versus non-responders. Current imaging techniques using F-fluorodeoxyglucose-positron-emmission-tomograpy (F-FDG-PET) cannot discriminate, at early treatment times, between tumor progression and inflammation.

In-depth Characterization of a TCR-specific Tracer for Sensitive Detection of Tumor-directed Transgenic T Cells by Immuno-PET.

A number of different technologies have been developed to monitor the distribution of gene-modified T cells used in immunotherapy. Nevertheless, in-depth characterization of novel approaches with respect to sensitivity and clinical applicability are so far missing. We have previously described a novel method to track engineered human T cells in tumors using Zr-Df-aTCRmu-F(ab') targeting the murinized part of the TCR beta domain (TCRmu) of a transgenic TCR.

Immuno-PET Imaging of Engineered Human T Cells in Tumors.

Sensitive in vivo imaging technologies applicable to the clinical setting are still lacking for adoptive T-cell-based immunotherapies, an important gap to fill if mechanisms of tumor rejection or escape are to be understood. Here, we propose a highly sensitive imaging technology to track human TCR-transgenic T cells in vivo by directly targeting the murinized constant TCR beta domain (TCRmu) with a zirconium-89 ((89)Zr)-labeled anti-TCRmu-F(ab')2 fragment. Binding of the labeled or unlabeled F(ab')2 fragment did not impair functionality of transgenic T cells in vitro and in vivo Using a murine xenograft model of human myeloid sarcoma, we monitored by Immuno-PET imaging human central memory T cells (TCM), which were transgenic for a myeloid peroxidase (MPO)-specific TCR.