α-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the α-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous α-particle emission distribution concentrated at bone-tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that 223Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of α-particle radiopharmaceutical therapies.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2023 Dec 14 [Epub ahead of print]
Nadia Benabdallah, Peng Lu, Diane S Abou, Hanwen Zhang, David Ulmert, Robert F Hobbs, Hiram A Gay, Brian W Simons, Muhammad A Saeed, Buck E Rogers, Abhinav K Jha, Yuan-Chuan Tai, Christopher D Malone, Joseph E Ippolito, Jeff Michalski, Jack W Jennings, Brian C Baumann, Russell K Pachynski, Daniel L J Thorek
Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri., Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California., Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland., Department of Radiation Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri., Center for Comparative Medicine, Baylor University, Houston, Texas., Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri., Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri; .