Feasibility study of ²²⁵Ac-PSMA-CY313 dosimetry in mCRPC patients using SPECT

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Therapy
• Medical Physics

Background:

• Actinium-225 (²²⁵Ac)-labeled PSMA radiopharmaceuticals show promise for metastatic castration-resistant prostate cancer (mCRPC).
• Accurate dosimetry is crucial for clinical implementation but challenging due to ²²⁵Ac's complex decay and alpha emissions.
• Quantitative imaging methods are needed to assess dose distributions for ²²⁵Ac-based therapies.

Purpose of the Study:

• To evaluate the feasibility of quantitative single photon emission computed tomography (SPECT)-based dosimetry for ²²⁵Ac-PSMA-CY313 therapy.
• To utilize gamma emissions from daughter radionuclides (francium-221 and bismuth-213) for quantitative imaging.
• To establish a framework for personalized dosimetry in targeted alpha therapy for mCRPC.

Main Methods:

• Four mCRPC patients received ²²⁵Ac-PSMA-CY313 and underwent multi-timepoint SPECT/CT and planar imaging.
• Quantitative SPECT reconstruction incorporated corrections for attenuation, scatter, resolution, and crosstalk.
• Absorbed doses were calculated using Monte Carlo simulations and ICRP reference phantoms, with volumes of interest defined by co-registered ¹⁸F-PSMA-CY313 PET/CT.

Main Results:

• High-quality quantitative SPECT imaging was achieved across all timepoints.
• Kidneys and liver received the highest absorbed doses among normal organs (1.55 ± 0.38 Gy and 1.07 ± 0.19 Gy, respectively).
• Soft-tissue lesions showed higher absorbed doses than bone metastases, and favorable tumor-to-critical organ dose ratios were observed, indicating a good therapeutic window.

Conclusions:

• Quantitative SPECT-based dosimetry for ²²⁵Ac-PSMA-CY313 therapy is clinically feasible with standard imaging systems.
• The methodology demonstrates preferential tumor targeting and acceptable organ-at-risk dose distributions.
• This approach supports the therapeutic potential of ²²⁵Ac-PSMA-CY313 for mCRPC and enables personalized dosimetry.