Lesion Absorbed Dose-Response Relationship in Patients with Metastatic Castration-Resistant Prostate Cancer...

Area of Science:

• Nuclear Medicine
• Medical Physics
• Oncology

Background:

• The relationship between absorbed dose (AD) and treatment response for [¹⁷⁷Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) in metastatic castration-resistant prostate cancer (mCRPC) is not well understood.
• Accurate dosimetry is crucial for optimizing RPT efficacy and patient outcomes.

Purpose of the Study:

• To investigate the relationship between absorbed dose (AD) and treatment response at both patient and individual lesion levels.
• To evaluate the feasibility of single-time-point (STP) dosimetry for treatment personalization in [¹⁷⁷Lu]Lu-PSMA-617 RPT.

Main Methods:

• Sixty-five mCRPC patients received [¹⁷⁷Lu]Lu-PSMA-617 RPT with serial SPECT/CT imaging.
• Both single-time-point (STP) and multiple-time-point voxelwise dosimetry were performed.
• Patient response was assessed by changes in serum prostate-specific antigen (PSA) and lesion SUVmax using [⁶⁸Ga]Ga-PSMA-11 PET/CT.

Main Results:

• A moderate negative correlation was observed between mean lesion AD and both patient and lesion responses.
• Patients receiving higher mean AD (>7.5 Gy) showed significantly better PSA response (70% vs. -5%) and longer biochemical progression-free survival (4.1 vs. 1.6 months).
• STP dosimetry underestimated AD by 8% on average but is feasible for clinical implementation; low kidney ADs suggest hydration may further reduce them.

Conclusions:

• A moderate absorbed dose-response relationship exists for [¹⁷⁷Lu]Lu-PSMA-617 RPT in mCRPC.
• Higher AD is associated with improved clinical outcomes, supporting dose optimization.
• STP dosimetry is a practical tool for personalizing [¹⁷⁷Lu]Lu-PSMA-617 RPT.