Fibroblast Activation Protein Inhibitor Theranostics: Early Clinical Translation

Yuriko Mori; Clemens Kratochwil; Uwe Haberkorn; Frederik L Giesel

doi:10.1016/j.cpet.2023.02.007

Fibroblast Activation Protein Inhibitor Theranostics: Early Clinical Translation

PET Clin. 2023 Jul;18(3):419-428. doi: 10.1016/j.cpet.2023.02.007. Epub 2023 Apr 6.

Authors

Yuriko Mori¹, Clemens Kratochwil², Uwe Haberkorn², Frederik L Giesel³

Affiliations

¹ Department of Nuclear Medicine, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany. Electronic address: yuriko.mori@med.uni-duesseldorf.de.
² Department of Nuclear Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
³ Department of Nuclear Medicine, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany; Department of Nuclear Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.

PMID: 37030981
DOI: 10.1016/j.cpet.2023.02.007

Abstract

Fibroblast activation protein (FAP)-targeted radioligand therapy offers a possibility of a novel cancer therapeutic strategy, aiming at tumor stroma1. Early clinical translations of FAP-tracers occurred as early as in the 1990s using antibodies, without substantial achievement further than the clinical phase II trial. The essential step toward the theranostic approach, with a conceptual combination of diagnostic and therapeutic emitters in a specific tracer, began with the implementation of small-molecule FAP-enzyme inhibitors (FAPI) in 2018. Currently, FAPI-04 and FAPI-46, containing DOTA-chelators with the possibility of radionuclide combination (Ga-68, Y-90, and Lu-177), are the compounds most widely used in the theranostic regimen.

Keywords: Clinical translation; FAPI; Fibroblast; Radioligand therapy; Theranostic.

Publication types

Review

MeSH terms

Fibroblasts / metabolism
Gallium Radioisotopes*
Humans
Membrane Proteins / metabolism
Neoplasms* / diagnostic imaging
Neoplasms* / drug therapy
Neoplasms* / metabolism
Positron Emission Tomography Computed Tomography
Precision Medicine
Yttrium Radioisotopes

Substances

Gallium-68
Gallium Radioisotopes
Yttrium-90
Yttrium Radioisotopes
Membrane Proteins