Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice
Abstract [68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-pos...
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doaj-b8ba989a518749f694bb6f9f3502d7a82021-08-01T11:26:19ZengNature Publishing GroupScientific Reports2045-23222021-07-0111111110.1038/s41598-021-94684-6Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model miceSu Bin Kim0In Ho Song1Yoo Sung Song2Byung Chul Lee3Arun Gupta4Jae Sung Lee5Hyun Soo Park6Sang Eun Kim7Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National UniversityDepartment of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang HospitalDepartment of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang HospitalDepartment of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang HospitalDepartment of Radiology and Imaging Institution: B.P. Koirala Institute of Health Sciences (BPKIHS)Department of Nuclear Medicine, Seoul National University College of MedicineDepartment of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang HospitalDepartment of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang HospitalAbstract [68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.https://doi.org/10.1038/s41598-021-94684-6 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Su Bin Kim In Ho Song Yoo Sung Song Byung Chul Lee Arun Gupta Jae Sung Lee Hyun Soo Park Sang Eun Kim |
spellingShingle |
Su Bin Kim In Ho Song Yoo Sung Song Byung Chul Lee Arun Gupta Jae Sung Lee Hyun Soo Park Sang Eun Kim Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice Scientific Reports |
author_facet |
Su Bin Kim In Ho Song Yoo Sung Song Byung Chul Lee Arun Gupta Jae Sung Lee Hyun Soo Park Sang Eun Kim |
author_sort |
Su Bin Kim |
title |
Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice |
title_short |
Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice |
title_full |
Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice |
title_fullStr |
Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice |
title_full_unstemmed |
Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice |
title_sort |
biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68ga]psma-11, in subcutaneous prostate cancer xenograft model mice |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-07-01 |
description |
Abstract [68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions. |
url |
https://doi.org/10.1038/s41598-021-94684-6 |
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