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Dosimetry of 177 Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: Correlations Between Pretherapeutic Imaging and Whole-Body Tumor Dosimetry with Treatment Outcomes
Open accessAbstract
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 = 0.62), and SUVmax of the parotids correlated with absorbed dose (r = 0.67). There was an inverse correlation between tumor volume and mean dose to the parotids (r = −0.41) and kidneys (r = −0.43). The mean parotid dose was also reduced with increasing body mass (r = −0.41) and body surface area (r = −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.
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“This scenario is common for many RPTs agents, and perhaps most prominently for prostate cancer ( 39 , 40 ), where metastatic dissemination is coincident with the marrow.”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [39]
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“In a phase 2 study of 28 patients who underwent 51 Cr-EDTA GFR measurement before and 3 mo after completion of 4 cycles of 177 Lu-PSMA, a very modest decline of approximately 12 mL/min in GFR was noted ( 39 , 68 , 69 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [69]
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“The dosimetry studies of small molecules targeting PSMA such as 124 I/ 131 I-MIP-1095, or 177 Lu-PSMA-617 or 177 Lu-PSMA I&T have shown salivary glands commonly receive the highest radiation-absorbed dose among normal organs ( 69 , 74 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [69]
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In the citing paper
“In a phase 2 study of 28 patients who underwent 51 Cr-EDTA GFR measurement before and 3 mo after completion of 4 cycles of 177 Lu-PSMA, a very modest decline of approximately 12 mL/min in GFR was noted ( 39 , 68 , 69 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [39]
Experimental — accuracy not yet measuredIn the citing paper
“High SUVmean values indicate high average PSMA expression levels, which may promote tumor binding and uptake of 177Lu-PSMA-617, leading to greater delivery of radiation and greater antitumor activity (18,19).”
From Quantitative 68 Ga-PSMA-11 PET and Clinical Outcomes in Metastatic Castration-resistant Prostate Cancer Following 177 Lu-PSMA-617 (VISION Trial) (2024) · cites this paper as [19]
In the citing paper
“High SUVmean values indicate high average PSMA expression levels, which may promote tumor binding and uptake of 177Lu-PSMA-617, leading to greater delivery of radiation and greater antitumor activity (18,19).”
From Quantitative 68 Ga-PSMA-11 PET and Clinical Outcomes in Metastatic Castration-resistant Prostate Cancer Following 177 Lu-PSMA-617 (VISION Trial) (2024) · cites this paper as [19]
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Additional file 1 of A machine learning-based model for a dose point kernel calculation
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“To assess the absorbed dose response for each lesion a threshold of > 10 Gy was used to identify responders (any kind of PSA response) and non-responders after an administration of 7.4 Gy 177 Lu-PSMA in a first fraction of treatment [37, 38].”
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The PSMA paradox: How biology, androgen signaling, and therapy sequencing shape Lu-177 efficacy
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“One new, promising therapy for patients with metastatic castration-resistant prostate cancer (mCRPC) is Lutetium-177 vipivotide tetraxetan ( 177 Lu-PSMA-617) [3].”
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Dose-intensified PSMA Radioligand Therapy: The Rationale Behind the OPTIMAL-PSMA Trial
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“This therapy provides a 3–6 times higher absorbed dose to the tumour than to the kidney and salivary glands [4, 5].”
Organ and tumor dosimetry of [161Tb]Tb-PSMA-617 radioligand therapy in patients with mCRPC
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“Accurate computation of the AD [38] to the bone marrow [39, 40], salivary glands, and lacrimal glands [5, 41, 42], needs to be addressed prior to defining toxicity thresholds.”
Theranostics in the management of prostate cancer: from concept to clinical practice
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“The concept of a sink effect, called “tumour-sink effect”, was first described in radio-theranostic studies which demonstrated that tumours may indeed behave as PK “sinks,” competing actively with normal tissues for drug uptake [35–37].”
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“The absorbed tumor dose delivered by [ 177 Lu]Lu-PSMA-617 correlates with tumor uptake on pretherapeutic PSMA-PET, and patients receiving a whole-body tumor dose below 10 Gy rarely achieve a PSA50 response [38].”
Metadata
- Authors
- Violet, J., Jackson, P., Ferdinandus, J., Sandhu, S., Akhurst, T., Iravani, A., Kong, G., Kumar, A. R., Thang, S. P., Eu, P., Scalzo, M., Murphy, D., Williams, S., Hicks, R. J., & Hofman, M. S.
- Affiliations
- Peter MacCallum Cancer Centre (AU)
- The University of Melbourne (AU)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2018-10-05
- Volume
- 60
- Issue
- 4
- Pages
- 517-523
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2895593497
- Cited by
- 504
- References
- 52
- Citations by year
- 2026: 69 · 2025: 71 · 2024: 85 · 2023: 75 · 2022: 61 · 2021: 81 · 2020: 38 · 2019: 22 · 2018: 2
- FWCI
- 24.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Australian Nuclear Science and Technology Organisation
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- 177Lu-PSMA-617, prostate-specific membrane antigen, castration-resistant prostate cancer, metastatic prostate cancer, radiation dosimetry, absorbed dose, PSMA PET/CT, 68Ga-PSMA-11, quantitative SPECT/CT, parotid gland dose, kidney dose, PSA response, treatment outcome prediction, body mass
- MeSH terms
- Single Photon Emission Computed Tomography Computed Tomography, Dipeptides, Heterocyclic Compounds, 1-Ring, Humans, Lutetium, Male, Neoplasm Metastasis, Radioisotopes, Radiometry, Treatment Outcome, Prostate-Specific Antigen, Prostatic Neoplasms, Castration-Resistant
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