First-in-Human ²¹²Pb-PSMA–Targeted α-Therapy SPECT/CT Imaging in a Patient with Metastatic Castration-Resistant Prostate Cancer

There is significant interest in the development of ²¹²Pb-PSMA–based targeted α-therapy for patients with metastatic castration-resistant prostate cancer. A previous phantom study has shown that ²¹²Pb SPECT is feasible by imaging the 238.6 keV and 75 to 91 keV γ-emissions produced after the β-decay of ²¹²Pb to its α-emitting progeny (1).

Here we present—to the best of our knowledge—the first human ²¹²Pb SPECT/CT images published to date. They were acquired after administration of 60 MBq of ²¹²Pb-ADVC001 to a 73-y-old man with metastatic castration-resistant prostate cancer. This study was approved by the local institutional review board. Imaging was at 1.5, 5, 20, and 28 h after infusion. Two simultaneous triple-energy window acquisitions (78 keV ± 20% with 20% scatter [31% abundance] and 239 keV ± 10% with 10% scatter [43% abundance] were obtained using a Siemens Intevo Bold (high-energy collimators at 30 s per view for 120 views per rotation at 2 bed positions with noncircular orbits; total time, 60 min). Each energy window was reconstructed independently, and the resulting images were summed with removal of Compton-based orbit artifacts.

Representative ²¹²Pb SPECT/CT images (Fig. 1) showed rapid tumor uptake of ²¹²Pb-ADVC001 highly concordant with tumor burden delineated on the pretreatment ¹⁸F-DCFPyl PET/CT images. Images acquired after 20 h showed persistent tumor uptake despite low counts due to ²¹²Pb decay (10.6 h half-life).

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 1.

(A) ¹⁸F-DCFPyl PET/CT and ²¹²Pb SPECT/CT images showing concordant tumor biodistribution with low salivary gland uptake (red arrow) and rapid kidney clearance of 60 MBq of ²¹²Pb-ADVC001. A 3-MBq standard solution (100 mL) was included. (B) Sagittal and coronal images at 1.5 h after injection (p.i.). MIP = maximum-intensity projection.

²¹²Pb is a challenging isotope to image because of the high-energy γ-rays from the lead progeny generating Compton scatter from the patient and collimator (1). Our approach of summing images reconstructed from both energy windows shows the feasibility and benefit of ²¹²Pb SPECT/CT imaging in providing postinfusion radiopharmaceutical biodistribution and patient-specific dosimetry for clinical development of ²¹²Pb-targeted α-therapy.

• © 2024 by the Society of Nuclear Medicine and Molecular Imaging.

• Received for publication December 1, 2023.
• Revision received January 23, 2024.