[⁶⁸Ga]Ga-NOTA-T4 ImmunoPET imaging for evaluating TROP2 expression in patients with solid tumors

Area of Science:

• Nuclear Medicine
• Oncology
• Radiochemistry

Background:

• Trophoblast cell-surface antigen 2 (TROP2) is a target for cancer therapies.
• Non-invasive imaging of TROP2 expression is crucial for guiding treatment decisions.
• Gallium-68 (⁶⁸Ga)-labeled tracers offer potential for immuno-positron emission tomography (immunoPET).

Purpose of the Study:

• To evaluate the diagnostic utility of ⁶⁸Ga-labeled [⁶⁸Ga]Ga-NOTA-T4 PET/CT for TROP2 expression in solid tumors.
• To compare the performance of [⁶⁸Ga]Ga-NOTA-T4 PET/CT with fluorine-18-labeled fluorodeoxyglucose ([¹⁸F]FDG) PET/CT.
• To assess the correlation between [⁶⁸Ga]Ga-NOTA-T4 uptake and TROP2 expression levels determined by immunohistochemistry.

Main Methods:

• Prospective recruitment of 26 patients with solid tumors undergoing [⁶⁸Ga]Ga-NOTA-T4 PET/CT.
• Quantification of tracer uptake using standardized uptake value (SUVmean, SUVmax) and target-to-background ratio (TBR).
• Immunohistochemical (IHC) tumor proportion score (TPS) was used to assess TROP2 expression.

Main Results:

• [⁶⁸Ga]Ga-NOTA-T4 showed expected biodistribution with high uptake in kidneys and pancreas, low in brain and muscle.
• Both tracers detected all primary/recurrent tumors, but [⁶⁸Ga]Ga-NOTA-T4 had lower SUVmax and TBR than [¹⁸F]FDG.
• [⁶⁸Ga]Ga-NOTA-T4 uptake positively correlated with TROP2 expression (TPS), unlike [¹⁸F]FDG, and detected two brain metastases missed by [¹⁸F]FDG.

Conclusions:

• [⁶⁸Ga]Ga-NOTA-T4 PET/CT is a promising non-invasive method for assessing TROP2 expression and diagnosing solid tumors.
• This tracer may offer advantages over [¹⁸F]FDG PET/CT in specific clinical scenarios, particularly for TROP2-targeted therapies.
• The correlation with IHC confirms the potential of [⁶⁸Ga]Ga-NOTA-T4 PET/CT to reflect actual TROP2 tumor burden.