Fibroblast Activation Protein-Directed Imaging Outperforms 18F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial

J Nucl Med. 2024 Aug 1;65(8):1188-1193. doi: 10.2967/jnumed.124.267473.

Abstract

The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a 68Ga-FAPI46 PET observational trial (NCT04571086). Methods: Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the 68Ga-FAPI46 PET observational trial. All patients underwent 68Ga-FAPI46 PET/CT, contrast-enhanced CT, and 18F-FDG PET/CT. The primary study endpoint was the association of 68Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with 18F-FDG PET/CT. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI46 SUVmax or SUVpeak and histopathologic FAP expression was significant (SUVmax: r = 0.49, P = 0.037; SUVpeak: r = 0.51, P = 0.030).68Ga-FAPI46 and 18F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher 68Ga-FAPI46 than 18F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). Conclusion: We confirm an association of 68Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for 68Ga-FAPI46 versus 18F-FDG.

Keywords: FAPI; cancer imaging; fibroblast activation protein; mesothelioma; thoracic cancer.

Publication types

  • Observational Study
  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Endopeptidases*
  • Female
  • Fluorodeoxyglucose F18*
  • Gelatinases* / metabolism
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / metabolism
  • Male
  • Membrane Proteins / metabolism
  • Mesothelioma* / diagnostic imaging
  • Mesothelioma* / metabolism
  • Mesothelioma, Malignant* / diagnostic imaging
  • Mesothelioma, Malignant* / metabolism
  • Middle Aged
  • Positron Emission Tomography Computed Tomography* / methods
  • Prospective Studies
  • Serine Endopeptidases / metabolism

Substances

  • Fluorodeoxyglucose F18
  • fibroblast activation protein alpha
  • Endopeptidases
  • Gelatinases
  • Membrane Proteins
  • Serine Endopeptidases