Dual targeting PET tracer [⁶⁸Ga]Ga-FAPI-RGD in patients with lung neoplasms: a pilot exploratory study

Abstract

Rationale: Early discovery, accurate diagnosis, and staging of lung cancer is essential for patients to receive appropriate treatment. PET/CT has become increasingly recognized as a valuable imaging modality for these patients, but there remains room for improvement in PET tracers. We aimed to evaluate the feasibility of using [ 68 Ga]Ga-FAPI-RGD, a dual-targeting heterodimeric PET tracer that recognizes both fibroblast activation protein (FAP) and integrin α v β 3 for detecting lung neoplasms, by comparing it with [ 18 F]FDG and single-targeting tracers [ 68 Ga]Ga-RGD and [ 68 Ga]Ga-FAPI. Methods: This was a pilot exploratory study of patients with suspected lung malignancies. All 51 participants underwent [ 68 Ga]Ga-FAPI-RGD PET/CT, of which: 9 participants received dynamic scans, 44 participants also underwent [ 18 F]FDG PET/CT scan within two weeks, 9 participants underwent [ 68 Ga]Ga-FAPI PET/CT scan and 10 participants underwent [ 68 Ga]Ga-RGD PET/CT scan. The final diagnosis was made based on histopathological analyses and clinical follow-up reports. Results: Among those who underwent dynamic scans, the uptake of pulmonary lesions increased over time. The optimal timepoint for a PET/CT scan was identified to be 2 h post-injection. [ 68 Ga]Ga-FAPI-RGD had a higher detection rate of primary lesions than [ 18 F]FDG (91.4% vs. 77.1%, p < 0.05), higher tumor uptake (SUVmax, 6.9 ± 5.3 vs. 5.3 ± 5.4, p < 0.001) and higher tumor-to-background ratio (10.0 ± 8.4 vs. 9.0 ± 9.1, p < 0.05), demonstrated better accuracy in mediastinal lymph node evaluation (99.7% vs. 90.9%, p < 0.001), and identified more metastases (254 vs. 220). There was also a significant difference between the uptake of [ 68 Ga]Ga-FAPI-RGD and [ 68 Ga]Ga-RGD of primary lesions (SUVmax, 5.8 ± 4.4 vs. 2.3 ± 1.3, p < 0.001). Conclusion: In our small scale cohort study, [ 68 Ga]Ga-FAPI-RGD PET/CT gave a higher primary tumor detection rate, higher tracer uptake, and improved detection of metastases compared with [ 18 F]FDG PET/CT, and [ 68 Ga]Ga-FAPI-RGD also had advantages over [ 68 Ga]Ga-RGD and was non-inferior to [ 68 Ga]Ga-FAPI. We thus provide proof-of-concept for using [ 68 Ga]Ga-FAPI-RGD PET/CT for diagnosing lung cancer. With the stated advantages, the dua...

Recent Pre-Clinical Advancements in Nuclear Medicine: Pioneering the Path to a Limitless Future

“…A clinical study carried out on 22 patients and recently published by Zhao et al demonstrated an improved lesion detection rate and metastatic delineation of 68 Ga-FAPI-RGD in comparison to 18 F-FDG [193]. Similar observations were reported in a pilot exploratory study on patients (n = 51) with suspected lung cancers [194]. With the stated advantages, the FAPI-RGD should be further explored for therapeutic applications.…”

Molecular Imaging for Lung Cancer: Exploring Small Molecules, Peptides, and Beyond in Radiolabeled Diagnostics

“…In a recent investigation, Wang et al [ 89 ] performed a pilot cohort study to assess the viability of [ 68 Ga]Ga-FAPi-RGD, a bifunctional PET tracer targeting both fibroblast-activating protein (FAP) and α v β 3 integrin, in identifying lung cancers. This tracer was evaluated alongside [ 18 F]F-FDG and the single-function tracers [ 68 Ga]Ga-RGD and [ 68 Ga]Ga-FAPi for lung cancer detection efficacy.…”

“…Additionally, it achieved superior precision in evaluating mediastinal lymph nodes (99.7% vs. 90.9%, p < 0.001) and detected more metastatic sites (254 vs. 220). A notable distinction was also observed in the uptake of primary lesions between [ 68 Ga]Ga-FAPi-RGD and [ 68 Ga]Ga-RGD (SUVmax, 5.8 ± 4.4 vs. 2.3 ± 1.3, p < 0.001) [ 89 ]. Radiolabeled fibroblast-activating protein (FAPI) inhibitors are significant markers for the non-invasive imaging of tumor microenvironments.…”

Fibroblast activation protein (FAP)-targeted radionuclide therapy: which ligand is the best?

“…A similar extensive study with radiolabeled FAPI multimers is warranted to arrive at a definitive conclusion. To enhance tumor uptake and retention, bi-specific heterodimeric radiotracers such as those targeting both FAPI and integrin α v β 3 (FAPI-RGD) have also been developed [20][21][22]. Such radiopharmaceuticals can overcome the compromised sensitivity and specificity, attributable to tumor heterogeneity and complexity of the mono-targeting radiotracers for potential therapeutic applications.…”