PET imaging lays foundation for new cancer therapies

2021 11 05 22 54 1166 2021 11 08 Fapi Pet Graphical Abstract 400

PET imaging of cancer patients with an experimental gallium-68 (Ga-68) tracer may be a reliable way to evaluate new therapies, according to a study published November 5 in the Journal of Nuclear Medicine.

A team at the University of California, Los Angeles (UCLA) analyzed the uptake of Ga-68-labeled fibroblast activation protein inhibitor (Ga-68 FAPI-46) in tumors after patients underwent PET scans. The group found uptake related strongly to levels of the protein found in subsequent biopsy lab tests.

"Ga-68 FAPI-46 PET biodistribution correlated strongly with FAP [fibroblast activation protein] expression in cancer and non-cancer tissues across multiple cancer types," wrote first author Christine Mona, PhD, of UCLA's department of molecular and medical pharmacology, and colleagues.

The finding lays the foundation for future evaluation of Fibroblast activation protein (FAP)-labeled therapeutic isotopes in clinical trials, the authors wrote.

FAP is overexpressed in cancer, and researchers suspect it is an essential component driving the growth of tumors. Experimental FAP-targeted molecular imaging agents, such as FAPI-04 and FAPI-46, have shown promising results in tumor diagnosis.

In this study, Mona and colleagues explored whether Ga-68 FAPI-46 PET biodistribution across various cancers "faithfully reflects" FAP expression as found in biopsied cancer and noncancer specimens.

The researchers first surveyed tissue microarrays of 141 patients with 14 cancer types for the presence and degree of FAP expression by immunohistochemistry. They then recruited 15 surgical patients representing 10 of those cancer types.

Volunteer patients underwent one whole-body Ga-68 FAPI-46 PET/CT scan (Biograph 64 mCT or Biograph 64 TruePoint, Siemens Healthineers) and subsequently, surgical resection of their primary or metastatic tumor. Lastly, the researchers compared Ga-68 FAPI-46 PET maximum standardized uptake values (SUVmax and SUVmean) with FAP immunohistochemistry scores in cancer and noncancer tissues for each patient.

Image courtesy of the Journal of Nuclear Medicine.Image courtesy of the Journal of Nuclear Medicine.

They found Ga-68 FAPI-46 SUVs and immunohistochemistry scores were higher in cancer than in normal tissue: mean SUVmax 7.7 vs. 1.6 (p < 0.001), mean SUVmean 6.2 vs. 1.0 (p < 0.001) and mean FAP immunohistochemistry score 2.8 vs. 0.9 (p < 0.001). In addition, FAP immunohistochemistry scores strongly correlated with Ga-68 FAPI-46 SUVmax (r = 0.781) and SUVmean (r = 0.783) across all cancer types.

"FAP was expressed across all cancer types with variable intensity and frequency. We established a positive and significant correlation between FAP-target expression and FAPI PET SUVs," the researchers wrote.

The main limitation of the study was the small sample size, the researchers noted. This was an exploratory study and local oversight committees mandated an interim analysis after the first 15 patients, they wrote.

Ultimately, the interim analysis revealed a highly significant correlation between immunohistochemistry and PET findings, which provided the motivation to publish the data, the researchers stated.

"These findings support further exploration of FAPI PET as a pan-cancer imaging biomarker for FAP expression and stratification tool for FAP-targeted therapies," the team concluded.

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