The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study protocol

Area of Science:

• Oncology
• Nuclear Medicine
• Radiology

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) exhibits significant inter-metastatic heterogeneity.
• Understanding this heterogeneity and neuroendocrine transdifferentiation is crucial for effective treatment.
• Current diagnostic methods may not fully capture the molecular diversity of mCRPC metastases.

Purpose of the Study:

• To determine the prevalence of intra-patient inter-metastatic heterogeneity in mCRPC using positron emission tomography (PET)/computed tomography (CT).
• To assess the prevalence of neuroendocrine disease in mCRPC patients.
• To evaluate patient eligibility for radioligand therapies (RLTs) based on molecular imaging findings.

Main Methods:

• A multicentre observational prospective study including 100 mCRPC patients.
• Triple-tracer PET/CT imaging using fluorine-18 fluorodeoxyglucose (18F-FDG), gallium-68 (68Ga)-PSMA-617, and 68Ga-DOTATATE.
• Assessment of tracer uptake in individual lesions to identify discordant profiles indicative of heterogeneity.

Main Results:

• The triple-tracer approach enables whole-body characterization of mCRPC.
• It facilitates the investigation of inter-metastatic heterogeneity and neuroendocrine transdifferentiation.
• Eligibility for PSMA- and DOTATATE-based RLTs can be assessed non-invasively.

Conclusions:

• This multi-tracer PET/CT strategy offers a novel, non-invasive method for detecting mCRPC heterogeneity and neuroendocrine transdifferentiation.
• It provides biologically relevant insights to personalize the care of mCRPC patients.
• The findings may establish a basis for new therapeutic strategies in mCRPC.