First interim results of a prospective phase I/II trial in different neoadjuvant treated cancers with [18F]FPyGal to detect therapy-induced-senescence

Ziel/Aim: Cellular senescence is an irreversible cell cycle arrest and plays a crucial role in the development of therapeutic resistance. Senescence is associated with a secretory phenotype, that can acquire pro-tumorigenic properties by secreting growth factors and cytokines. Therefore, non-invasive detection of senescence is desirable to modulate future senomorphic and senolytic treatments. Here we report the first results of a prospective phase I/II study using the recently developed PET tracer [¹⁸F]FPyGal for the non-invasive assessment of senescence in neoadjuvantly treated cancers.

Methodik/Methods: Initially, 8 healthy volunteers underwent dynamic PET/CT with [¹⁸F]FPyGal for safety and dosimetry. To date, 22 of 27 patients with rectal (4), esophageal (7) or lung (11) cancer after neoadjuvant therapy have been recruited. All scans were performed on either a PET/MRI or a LAFOV PET/CT scanner. Safety parameters were assessed before and after imaging. Several PET parameters such as SUVmean and the tumor-to-liver ratio (TLR) were evaluated for the dynamic scans of at least 60 min. The presence of senescence markers including p16, p21, p53, and X-Gal staining was investigated after tumor resection.

Ergebnisse/Results: The phase I clinical study demonstrated the safety of [¹⁸F]FPyGal in healthy volunteers with no significant adverse effects. A relatively low effective whole-body radiation dose (8.1±0.2 μSv/MBq) was observed. Preliminary analysis of cancer patients revealed heterogeneous [¹⁸F]FPyGal uptake in many tumors. Areas with increased beta-galactosidase activity in X-Gal staining showed a higher TLR ratio. In addition, tumor regions were classified as senescence positive or negative by a blinded pathologist based on the presence of senescence markers. The senescence positive areas tended to have higher TLR than the control areas.

Schlussfolgerungen/Conclusions: In this prospective phase I/II study, we demonstrated that [¹⁸F]FPyGal is well tolerated and the effective radiation dose is acceptable. Initial results supports the feasibility of non-invasive in vivo detection of senescence by [¹⁸F]FPyGal PET.

Publikationsverlauf

Artikel online veröffentlicht:
12. März 2025