Dosimetry of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: Correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes

John Violet, Price Jackson, Justin Ferdinandus, Shahneen Sandhu, Tim Akhurst, Amir Iravani, Grace Kong, Aravind Ravi Kumar, Sue Ping Thang, Peter Eu, Mark Scalzo, Declan Murphy, Scott Williams, Rodney J. Hicks, Michael S. Hofman

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

177Lu-prostate-specific membrane antigen (PSMA)–617 enables targeted delivery of β-particle radiation to prostate cancer. We determined its radiation dosimetry and relationships to pretherapeutic imaging and outcomes. Methods: Thirty patients with prostate cancer receiving 177Lu-PSMA-617 within a prospective clinical trial (ACTRN12615000912583) were studied. Screening 68Ga-PSMA-11 PET/CT demonstrated high PSMA expression in all patients. After therapy, patients underwent quantitative SPECT/CT at 4, 24, and 96 h. Pharmacokinetic uptake and clearance at a voxel level were calculated and translated into absorbed dose using voxel S values. Volumes of interest were drawn on normal tissues and tumor to assess radiation dose, and a whole-body tumor dose was defined. Correlations between PSMA PET/CT parameters, dosimetry, and biochemical and therapeutic response were analyzed to identify relationships between absorbed dose, tumor burden, and patient physiology. Results: Mean absorbed dose to kidneys, submandibular and parotid glands, liver, spleen, and bone marrow was 0.39, 0.44, 0.58, 0.1, 0.06, and 0.11 Gy/MBq, respectively. Median whole-body tumor-absorbed dose was 11.55 Gy and correlated with prostate-specific antigen (PSA) response at 12 wk. A median dose of 14.1 Gy was observed in patients achieving a PSA decline of at least 50%, versus 9.6 Gy for those achieving a PSA decline of less than 50% (P, 0.01). Of 11 patients receiving a tumor dose of less than 10 Gy, only one achieved a PSA response of at least 50%. On screening PSMA PET, whole-body tumor SUVmean correlated with mean absorbed dose (r 5 0.62), and SUVmax of the parotids correlated with absorbed dose (r 5 0.67). There was an inverse correlation between tumor volume and mean dose to the parotids (r 5 −0.41) and kidneys (r 5 −0.43). The mean parotid dose was also reduced with increasing body mass (r 5 −0.41) and body surface area (r 5 −0.37). Conclusion: 177Lu-PSMA-617 delivers high absorbed doses to tumor, with a significant correlation between whole-body tumor dose and PSA response. Patients receiving less than 10 Gy were unlikely to achieve a fall in PSA of at least 50%. Significant correlations between aspects of screening 68Ga-PET/CT and tumor and normal tissue dose were observed, providing a rationale for patient-specific dosing. Reduced salivary and kidney doses were observed in patients with a higher tumor burden. The parotid dose also reduced with increasing body mass and body surface area.

Original languageEnglish
Pages (from-to)517-523
Number of pages7
JournalJournal of Nuclear Medicine
Volume60
Issue number4
DOIs
StatePublished - Apr 1 2019

Keywords

  • Dosimetry
  • Lu-PSMA-617
  • Prostate cancer
  • Radionuclide therapy
  • Theranostics

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