Unveiling the Tumor Microenvironment Through Fibroblast Activation Protein Targeting in Diagnostic Nuclear Medicine: A Didactic Review on Biological Rationales and Key Imaging Agents.

The tumor microenvironment (TME) is a dynamic and complex medium that plays a central role in cancer progression, metastasis, and treatment resistance. Among the key elements of the TME, cancer-associated fibroblasts (CAFs) are particularly important for their ability to remodel the extracellular matrix, promote angiogenesis, and suppress anti-tumor immune responses. Fibroblast activation protein (FAP), predominantly expressed by CAFs, has emerged as a promising target in both cancer diagnostics and therapeutics.

GMP-Compliant Automated Radiolabeling and Quality Controls of [Ga]Ga-FAPI-46 for Fibroblast Activation Protein-Targeted PET Imaging in Clinical Settings.

In nuclear medicine, molecular imaging of the tumor microenvironment using radiopharmaceuticals (RPs) targeting cancer-associated fibroblasts is gaining significant interest. Among these RPs, [Ga]Ga-FAPI-46 for positron emission tomography (PET) imaging is frequently used in clinical research protocols. To ensure that the production of this RP complies with good manufacturing practices, process automation is widely adopted.

Towards Optimal Automated Ga-Radiolabeling Conditions of the DOTA-Bisphosphonate BPAMD Without Pre-Purification of the Generator Eluate.

DOTA-functionalized bisphosphonates can be useful tools for PET imaging of bone metastases when radiolabeled with Ga. Moreover, the versatility of DOTA allows the complexation of radiometals with therapeutic applications (e.g.

"One Method to Label Them All": A Single Fully Automated Protocol for GMP-Compliant Ga Radiolabeling of PSMA-11, Transposable to PSMA-I&T and PSMA-617.

Background: Prostate-specific membrane antigen (PSMA) is an ideal target for molecular imaging and targeted radionuclide therapy in prostate cancer. Consequently, various PSMA ligands were developed. Some of these molecules are functionalized with a chelator that can host radiometals, such as Ga for PET imaging.

[Ga]Ga-FAPI-46 synthesis on a GAIA® module system: Thorough study of the automated radiolabeling reaction conditions.

The influence of several parameters involved in the Ga radiolabeling of FAPI-46 was studied at the scale of the automated reaction. Among the buffers tested, HEPES 0.3 M pH 4 allowed both high radiochemical purity (RCP) and radiochemical yield (RCY), without prepurification of Ga but after final purification of [Ga]Ga-FAPI-46 on a C cartridge.