Dr. Giesel started by highlighting that the theranostic approach merges imaging with therapy. Accumulation of PSMA imaging data has led to individual patient stratification according to prostate cancer tumor load, with PSMA expression increasing with greater Gleason score. In situations where there is concordance between PSMA and FDG (PSMA +/FDG – or PSMA +/FDG -), Dr. Giesel feels that these patients are suitable for a potential PSMA ligand therapy, whereas if there is discordance (PSMA- /FDG + or PSMA +/FDG + discordant) in imaging, these patients are not suitable.
A new ligand introduced by Dr. Giesel is FAPI (fibroblast activation protein inhibitor), targeting cancer-associated fibroblasts, which is a key component of the tumor microenvironment.1
Cancer-associated fibroblasts (CAFs) have a changed structure with increased collagen-I secretion and support for growth and metastasis of carcinomas. Tumors must have a certain size (~3mm cell cluster), at which time CAFs are produced.
Whereas the PSMA-ligand targets one specific cancer type (prostate cancer), the FAPI-ligand is beyond one specific cancer type. In preliminary work comparing 68Ga-FAPI-PET to 18F-FDG-PET, 68Ga-FAPI-PET matches nicely with 18F-FDG-PET, however, the benefit of 68Ga-FAPI-PET is that we only see CAF regions highlighted on the image rather than general glucose metabolism. Showing unpublished work from his institution (Heidelberg University Hospital), Dr. Giesel notes that in late-stage prostate cancer where PSMA imaging may be weak, FAPI-ligand imaging produces a strong, clear image:
Dr. Giesel’s group recently assessed tissue biodistribution and preliminary dosimetry testing of 68Ga-FAPI-2 and 68Ga-FAPI-4 in 2 patients at 0.2 hours, 1 hour, and 3 hours after tracer injection using the QDOSE dosimetry software suit.2 Further PET/CT scans of tumor patients were acquired 1 h after injection of either 68Ga-FAPI-2 (n = 25) or 68Ga-FAPI-4 (n = 25). They found that similar to literature values for 18F-FDG, 68Ga-DOTATATE, and 68Ga-PSMA-11, examination with 200 MBq of 68Ga-FAPI-2 or 68Ga-FAPI-4 corresponds to an equivalent dose of approximately 3-4 mSv. Additionally, in 68Ga-FAPI-2, the tumor uptake from 1 to 3 hours after injection decreased by 75%, whereas the tumor retention was prolonged with 68Ga-FAPI-4 (25% washout). Finally, the background uptake in brain (11.01 vs. 0.32), liver (2.77 vs. 1.69), and oral/pharyngeal mucosa (4.88 vs. 2.57) were significantly lower with 68Ga-FAPI.
Dr. Giesel concluded his presentation with several take-home messages:
- FAPI-PET/CT is a new diagnostic method in imaging cancer patients
- In contrast to FDG, no diet/fasting is necessary for the preparation of the exam, and image acquisition can potentially be started a few minutes after tracer application
- FAPI is similar to FDG as a multi-tumor tracer and will open the door for new innovative theranostics to respond to the high demand for patient care
- FAPI provides a new application for PSMA-negative prostate cancer patients
Presented by: Frederik L. G. Giesel, MD, MBA, Heidelberg University Hospital, Heidelberg, Germany
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 12th European Multidisciplinary Congress on Urological Cancers (EMUC) (#EMUC20 ), November 13th - 14th, 2020
References:
- Attieh Y, Vignjevic DM. The hallmarks of CAFs in cancer invasion. Eur J Cell Biol. 2016 Nov;95(11):493-502.
- Giesel FL, Kratochwil C, Linder T, et al. 68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers. J Nucl Med. 2019 Mar;60(3):386-392.