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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Cancer cell infiltration of the marrow is common for many RPT agents, and perhaps most prominently for prostate cancer, where metastatic dissemination is coincident with the marrow.
“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]
The Discussion (page not provided) describes metastatic burden in the axial skeleton of men with prostate cancer and says tumor likely confounded measurements intended to capture noninfiltrated marrow. This supports overlap between metastases and marrow in this setting, but the paper does not establish that marrow infiltration is common across many RPT agents or especially prominent in prostate cancer compared with other cancers. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn a phase 2 study of 28 patients who underwent 51Cr-EDTA GFR measurement before and 3 months after completion of 4 cycles of 177Lu-PSMA, a very modest decline of approximately 12 mL/min in GFR was noted.
“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]
Study Design and Patient Population reports 30 patients receiving up to four cycles of 177Lu-PSMA-617, and the Discussion reports no acute renal toxicity (page numbers unavailable). Neither section reports 51Cr-EDTA GFR measurements in 28 patients, a three-month post-treatment assessment, or a decline of approximately 12 mL/min. (LLM, conf=0.82)
Experimental — accuracy not yet measuredDosimetry studies of small molecules targeting PSMA have shown that salivary glands commonly receive the highest radiation-absorbed dose among normal organs.
“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]
In a phase 2 study of 28 patients who underwent 51Cr-EDTA GFR measurement before and 3 months after completion of 4 cycles of 177Lu-PSMA, a very modest decline of approximately 12 mL/min in GFR was noted.
“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]
Study Design and Patient Population describes 30 patients receiving up to four cycles of 177Lu-PSMA-617, and the Discussion reports no acute renal toxicity. Neither section reports 51Cr-EDTA GFR measurements before and three months after treatment, a 28-patient analysis, or a decline of approximately 12 mL/min (searched for 51Cr-EDTA and the stated GFR decline). (LLM, conf=0.74)
Experimental — accuracy not yet measuredHigh average PSMA expression may promote tumor binding and uptake of 177Lu-PSMA-617, leading to greater delivery of radiation and greater antitumor activity.
“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).”
High SUVmean values indicate high average PSMA expression levels.
“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).”
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Self-citationFerdinandus, J., Violet, J. A., Sandhu, S. K., Hicks, R. J., Kumar, A. S. R., Iravani, A., Kong, G., Akhurst, T. J., Thang, S. P., Murphy, D. G., et al. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-04723-z · Cited by 165 · see citing works
“Previously, we have reported that uptake intensity on PSMA-PET correlates with delivered radiation dose [Gy] in patients treated with LuPSMA, as well as PSA response at 12 weeks [7].”
MethodSelf-citationSeifert, R., Kessel, K., Schlack, K., Weber, M., Herrmann, K., Spanke, M., Fendler, W. P., Hadaschik, B., Kleesiek, J., Schäfers, M., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05040-1 · Cited by 160 · see citing works
“In line with the concept of theranostics, high SUVmean is associated with higher tumor doses of Lu-PSMA therapy and should therefore be linked to a favorable outcome [25].”
BackgroundBoschi, A., Uccelli, L., & Martini, P. (2019) · Applied Sciences · doi:10.3390/app9122526 · Cited by 140 · see citing works
Seifert, R., Seitzer, K. E., Herrmann, K., Kessel, K., Schäfers, M. A., Kleesiek, J., Weckesser, M., Boegemann, M., & Rahbar, K. (2020) · Theranostics · doi:10.7150/thno.47251 · Cited by 138 · see citing works
“had shown that the mean whole body PSMA PET uptake indeed correlated with the absorbed doses of Lu-PSMA therapy [32].”
BackgroundJackson, P. A., Hofman, M. S., Hicks, R. J., Scalzo, M., & Violet, J. A. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.233411 · Cited by 138 · see citing works
Self-citationFizazi, K., Herrmann, K., Krause, B. J., Rahbar, K., Chi, K. N., Morris, M. J., Sartor, O., Tagawa, S. T., Kendi, A. T., Vogelzang, N., et al. (2023) · The Lancet Oncology · doi:10.1016/s1470-2045(23)00158-4 · Cited by 125 · see citing works
Current, K., Meyer, C. A. L., Magyar, C. E., Mona, C. E., Almajano, J., Slavik, R., Stuparu, A. D., Cheng, C., Dawson, D. W., Radu, C. G., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1485 · Cited by 124 · see citing works
“Indeed, first clinical data suggest that (68)Ga-PSMA uptake (SUV) on pretherapy PET/CT correlates with the absorbed (177)Lu-PSMA dose and prostate-specific antigen response (37, 47, 48).”
BackgroundICRU REPORT 96, Dosimetry-Guided Radiopharmaceutical Therapy
Sgouros, G., Bolch, W. E., Chiti, A., Dewaraja, Y. K., Emfietzoglou, D., Hobbs, R. F., Konijnenberg, M., Gleisner, K. S., Strigari, L., Yen, T., et al. (2021) · Journal of the ICRU · doi:10.1177/14736691211060117 · Cited by 130 · see citing works
Current Status of Radiopharmaceutical Therapy
James, S. S., Bednarz, B. P., Benedict, S., Buchsbaum, J. C., Dewaraja, Y. K., Frey, E. C., Hobbs, R. F., Grudzinski, J. J., Roncali, E., Sgouros, G., et al. (2020) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2020.08.035 · Cited by 121 · see citing works
FAP: The Next Billion Dollar Nuclear Theranostics Target?
Calais, J. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.241232 · Cited by 115 · see citing works
“As another potential application, combining FAP-targeted with PSMA-targeted MRT may increase radiation doses in stroma-rich prostate cancer lesions (13,14).”
MethodNeuroendocrine Differentiation of Prostate Cancer—An Intriguing Example of Tumor Evolution at Play
Patel, G. K., Chugh, N., & Tripathi, M. (2019) · Cancers · doi:10.3390/cancers11101405 · Cited by 114 · see citing works
Kuo, P. H., Morris, M. J., Hesterman, J., Kendi, A. T., Rahbar, K., Wei, X. X., Fang, B., Adra, N., Garje, R., Michalski, J. M., et al. (2024) · Radiology · doi:10.1148/radiol.233460 · Cited by 119 · see citing works
“High SUV mean values indicate high average PSMA expression levels, which may promote tumor binding and uptake of 177 Lu-PSMA-617, leading to greater delivery of radiation and greater antitumor activity (18,19).”
Privé, B. M., Peters, S. M. B., Muselaers, S., van Oort, I. M., Janssen, M. J. R., Sedelaar, J. P. M., Konijnenberg, M., Zámecnik, P., Uijen, M. J. M., Schilham, M. G. M., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4298 · Cited by 100 · see citing works
Morgan, K. A., Rudd, S. E., Noor, A., & Donnelly, P. S. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00456 · Cited by 100 · see citing works
Deep neural network for automatic characterization of lesions on 68Ga-PSMA-11 PET/CT
Zhao, Y. S., Gafita, A., Vollnberg, B., Tetteh, G., Haupt, F., Afshar‐Oromieh, A., Menze, B. H., Eiber, M. J., Rominger, A., & Shi, K. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04606-y · Cited by 98 · see citing works
“Clinical research findings show that PC tumor burden and corresponding therapeutic radioligand dose received by the tumor correlate with the treatment response of PSMAdirected radioligand therapy [39].”
BackgroundLutetium Lu 177 Vipivotide Tetraxetan: First Approval
Keam, S. J. (2022) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-022-00594-2 · Cited by 98 · see citing works
Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns
Wahl, R. L., Sgouros, G., Iravani, A., Jacene, H., Pryma, D., Saboury, B., Capala, J., & Graves, S. A. (2021) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.262751 · Cited by 95 · see citing works
Self-citationKuo, H., Lin, K., Zhang, Z., Uribe, C., Merkens, H., Zhang, C., & Bénard, F. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.250738 · Cited by 94 · see citing works
“Since bone marrow radiation exposure is driven primarily by secondary exposure from bone metastases (36), the use of an albumin binder is not likely to lower the risk of hematologic toxicity.”
BackgroundLückerath, K., Liu, W., Fendler, W. P., Axelsson, S. E., Stuparu, A. D., Slavik, R., Mona, C. E., Calais, J., Rettig, M. B., Reiter, R. E., et al. (2018) · EJNMMI Research · doi:10.1186/s13550-018-0451-z · Cited by 91 · see citing works
Dosimetry in Radiopharmaceutical Therapy
O’Donoghue, J. A., ZANZONICO, P. B., Humm, J. L., & Kesner, A. (2022) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.262305 · Cited by 91 · see citing works
Eapen, R. S., Buteau, J. P., Jackson, P. A., Mitchell, C., Oon, S. F., Alghazo, O., McIntosh, L., Dhiantravan, N., Scalzo, M., O'Brien, J. S., et al. (2023) · European Urology · doi:10.1016/j.eururo.2023.08.026 · Cited by 91 · see citing works
Self-citationPattison, D. A., Debowski, M., Gulhane, B., Arnfield, E. G., Pelecanos, A. M., Garcia, P. L., Latter, M. J., Lin, C. Y., Roberts, M. J., Ramsay, S. C., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05520-y · Cited by 90 · see citing works
“The first of these, [68Ga]Ga-PSMA-11 rapidly became commonly used and suggested as the new standard of care for staging [4], re-staging at biochemical recurrence [5] and theranostic approach to prostate malignancy [6] given its superior sensitivity and specificity, interobserver reliability [7] and correlation with [1…”
MethodKratochwil, C., Giesel, F. L., Heußel, C. P., Kazdal, D. N., Endris, V., Nientiedt, C., Bruchertseifer, F., Kippenberger, M., Rathke, H. G., Leichsenring, J., et al. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.234559 · Cited by 91 · see citing works
“However, only a moderate correlation of pretherapy SUVs, tumor-absorbed dose, and treatment response was observed (6,7).”
BackgroundPeters, S. M. B., Privé, B. M., de Bakker, M., de Lange, F., Jentzen, W., Eek, A., Muselaers, C. H. J., Mehra, N., Witjes, J. A., Gotthardt, M., et al. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05471-4 · Cited by 88 · see citing works
“In these patients, a significant correlation between total lesion volume absorbed dose and PSA response was observed, but not when considering index lesions only [23].”
BackgroundResultProstate-specific Membrane Antigen PET in Prostate Cancer
Lawhn-Heath, C. A., Salavati, A., Behr, S. C., Rowe, S. P., Calais, J., Fendler, W. P., Eiber, M., Emmett, L., Hofman, M. S., & Hope, T. A. (2021) · Radiology · doi:10.1148/radiol.2021202771 · Cited by 89 · see citing works
Self-citationTumor Sink Effect in 68Ga-PSMA-11 PET: Myth or Reality?
Gafita, A., Wang, H., Robertson, A., Armstrong, W. R., Zaum, R., Weber, M., Yagubbayli, F., Kratochwil, C., Grogan, T., Nguyen, K., et al. (2021) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.261906 · Cited by 84 · see citing works
“Dosimetry data from the same cohort showed that a higher absorbed dose to tumor was associated with higher rates of PSA response and that tumor volume delineated on pretherapeutic (68)Ga-PSMA PET is inversely correlated with salivary gland and kidney absorbed radiation dose (25).”
BackgroundSelf-citationToward Single-Time-Point Image-Based Dosimetry of177Lu-PSMA-617 Therapy
Brosch-Lenz, J., Delker, A., Völter, F., Unterrainer, L. M., Kaiser, L., Bartenstein, P., Ziegler, S. I., Rahmim, A., Uribe, C., & Böning, G. (2023) · Journal of Nuclear Medicine · doi:10.2967/jnumed.122.264594 · Cited by 84 · see citing works
“The possibility of correlating pretherapy information with dosimetry and patient outcome was recently shown (10) and should motivate the community to implement routine dosimetry within RPTs and actively plan and adapt an RPT to personalize treatment and maximize patient therapeutic benefit.”
Backgroundvan der Doelen, M. J., Mehra, N., van Oort, I. M., Looijen-Salamon, M. G., Janssen, M. J. R., Custers, J. A. E., Slootbeek, P. H. J., Kroeze, L. I., Bruchertseifer, F., Morgenstern, A., et al. (2021) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2020.12.002 · Cited by 85 · see citing works
Application and Importance of Theranostics in the Diagnosis and Treatment of Cancer
Jeyamogan, S., Khan, N. A., & Siddiqui, R. (2021) · Archives of Medical Research · doi:10.1016/j.arcmed.2020.10.016 · Cited by 78 · see citing works
Herrmann, K., Rahbar, K., Eiber, M., Sparks, R. B., Baca, N., Krause, B. J., Laßmann, M., Jentzen, W., Tang, J., Chicco, D., et al. (2023) · Journal of Nuclear Medicine · doi:10.2967/jnumed.123.265448 · Cited by 77 · see citing works
“Data for lacrimal glands have previously been reported with a wide range of values and high variability ( 10 , 17 , 42 , 43 , 45 ).”
BackgroundResultDosimetry in radionuclide therapy: the clinical role of measuring radiation dose
Lawhn-Heath, C., Hope, T. A., Martinez, J., Fung, E. K., Shin, J., Seo, Y., & Flavell, R. R. (2022) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00657-4 · Cited by 75 · see citing works
Peters, S. M. B., Hofferber, R., Privé, B. M., de Bakker, M., Gotthardt, M., Janssen, M. J. R., de Lange, F., Muselaers, S., Mehra, N., Witjes, J. A., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05538-2 · Cited by 75 · see citing works
Radionuclide Therapy of Metastatic Prostate Cancer
Kratochwil, C., Haberkorn, U., & Giesel, F. L. (2019) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2019.02.003 · Cited by 74 · see citing works
Iravani, A., Violet, J., Azad, A., & Hofman, M. S. (2020) · Prostate Cancer and Prostatic Diseases · doi:10.1038/s41391-019-0174-x · Cited by 68 · see citing works
“The dosimetry studies have shown salivary gland receive the highest absorbed dose, median 4 Gy/GBq, among all other normal organs [21].”
BackgroundMethodInfluentialSelf-citationPathmanandavel, S., Crumbaker, M., Ho, B., Yam, A. O. W., Wilson, P., Niman, R., Ayers, M., Sharma, S., Hickey, A. J., Eu, P., et al. (2022) · Journal of Nuclear Medicine · doi:10.2967/jnumed.122.264398 · Cited by 68 · see citing works
Self-citationAbdollahi, H., Yousefirizi, F., Shiri, I., Brosch-Lenz, J., Mollaheydar, E., Fele‐Paranj, A., Shi, K., Zaidi, H., Alberts, I., Soltani, M., et al. (2024) · Theranostics · doi:10.7150/thno.93973 · Cited by 68 · see citing works
“In fact, in current non-personalized paradigms, the range of absorbed doses to organs-at-risk (e.g. salivary glands) can span an order of magnitude [20] resulting in conservative schemes in practice where many of patients are undertreated.”
BackgroundImplications of physics, chemistry and biology for dosimetry calculations using theranostic pairs
Miller, C., Rousseau, J., Ramogida, C. F., Celler, A. M., Rahmim, A., & Uribe, C. (2021) · Theranostics · doi:10.7150/thno.62851 · Cited by 67 · see citing works
“For example, [68Ga]Ga-PSMA-11 (PSMA being prostate specific membrane antigen) and [177Lu]Lu-PSMA-617 [38] for prostate cancer.”
MethodElls, Z., Grogan, T., Czernin, J. G., Dahlbom, M., & Calais, J. (2024) · Journal of Nuclear Medicine · doi:10.2967/jnumed.124.267452 · Cited by 68 · see citing works
Rathke, H. G., Holland‐Letz, T., Mier, W., Flechsig, P., Mavriopoulou, E., Röhrich, M., Kopka, K., Hohenfellner, M., Giesel, F. L., Haberkorn, U., et al. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.231431 · Cited by 64 · see citing works
“61) between PSMA PET and tumor uptake during therapy was found (19).”
BackgroundResultDhiantravan, N., Emmett, L., Joshua, A. M., Pattison, D. A., Francis, R. J., Williams, S., Sandhu, S. K., Davis, I. D., Vela, I., Neha, N., et al. (2021) · British Journal of Urology · doi:10.1111/bju.15384 · Cited by 64 · see citing works
Self-citationPSMA Theranostics: Current Landscape and Future Outlook
Zhang, H., Koumna, S., Pouliot, F., Beauregard, J., & Kolinsky, M. P. (2021) · Cancers · doi:10.3390/cancers13164023 · Cited by 64 · see citing works
“Higher PSMA-avidity is associated with higher radioligand uptake which allows cancer lesions to be exposed to a higher radiation dose [30].”
BackgroundLing, S. W., de Blois, E., Hooijman, E. L., Veldt, A. A. M. V. D., & Brabander, T. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14102166 · Cited by 63 · see citing works
Rydèn, T., van Essen, M., Marin, I., Svensson, J., & Bernhardt, P. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.245548 · Cited by 60 · see citing works
“With the introduction of 177Lu-PSMA for metastatic prostate cancer, SPECT/CT dosimetry requires 2-3 bed positions to cover the critical organs: salivary gland, bone marrow, kidneys, and targets in the pelvis region (21,24).”
BackgroundMethodPathmanandavel, S., Crumbaker, M., Yam, A. O. W., Nguyen, A., Rofe, C., Hovey, E. J., Gedye, C. A., Kwan, E. M., Hauser, C., Azad, A., et al. (2021) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.262552 · Cited by 60 · see citing works
“Further, dosimetry studies have shown that SUVmean correlates with the mean absorbed radiation dose and treatment response (13).”
BackgroundSelf-citationJeitner, T. M., Babich, J. W., & Kelly, J. M. (2022) · Translational Oncology · doi:10.1016/j.tranon.2022.101450 · Cited by 61 · see citing works
Maffey-Steffan, J., Scarpa, L., Svirydenka, A., Nilica, B., Mair, C., Buxbaum, S., Bektić, J., von Guggenberg, E., Uprimny, C., Horninger, W., et al. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04583-2 · Cited by 60 · see citing works
Personalized Dosimetry in Targeted Radiation Therapy: A Look to Methods, Tools and Critical Aspects
Danieli, R., Milano, A., Gallo, S., Veronese, I., Lascialfari, A., Indovina, L., Botta, F., Ferrari, M. E., Cicchetti, A., Raspanti, D., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12020205 · Cited by 60 · see citing works
“177Lu-PSMA (mCRPC) 30 Tumor response (PSA, 68Ga-PET/CT) “Whole-body” tumor absorbed dose [48]”
BackgroundSchaefer-Schuler, A., Burgard, C., Blickle, A., Maus, S., Petrescu, C., Petto, S., Bartholomä, M. D., Stemler, T., Ezziddin, S., & Rosar, F. (2024) · Theranostics · doi:10.7150/thno.92273 · Cited by 59 · see citing works
“Relatively high inter-patient variability of absorbed doses in tumor lesions has previously also been reported in several studies for [ 177 Lu]Lu-PSMA-617 as well as for other PSMA ligands as e.g. [ 177 Lu]Lu-PSMA I&T [50,52,53].”
InfluentialCopper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT
Hao, G., Mastren, T., Silvers, W. C., Hassan, G., Öz, O. K., & Sun, X. (2021) · Scientific Reports · doi:10.1038/s41598-021-82812-1 · Cited by 57 · see citing works
Rosar, F., Kochems, N., Bartholomä, M. D., Maus, S., Stemler, T., Linxweiler, J., Khreish, F., & Ezziddin, S. (2021) · Cancers · doi:10.3390/cancers13123095 · Cited by 59 · see citing works
Rosar, F., Schön, N., Bohnenberger, H., Bartholomä, M. D., Stemler, T., Maus, S., Khreish, F., Ezziddin, S., & Schaefer-Schuler, A. (2021) · EJNMMI Physics · doi:10.1186/s40658-021-00385-4 · Cited by 55 · see citing works
“So far, only a few studies using 3D dosimetry in PSMARLT have been published [37, 38].”
BackgroundRahmim, A., Brosch-Lenz, J., Fele‐Paranj, A., Yousefirizi, F., Soltani, M., Uribe, C., & Saboury, B. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1062592 · Cited by 55 · see citing works
“It is important to remember, as mentioned in the introduction, that uncertainties in absorbed doses by organs-at-risk (max:min) span an order of magnitude in current non-personalized RPT practice (16, 17).”
BackgroundYazdani, E., Geramifar, P., Ziarati, N. K., Sadeghi, M., Amini, P., & Rahmim, A. (2024) · Diagnostics · doi:10.3390/diagnostics14020181 · Cited by 55 · see citing works
“The original cohort study by Violet et al. [79] pointed out that SUV values on [ 68 Ga]Ga-PSMA PET/CT correlated with the AD of [ 177 Lu]Lu-PSMA RPT and PSA response.”
MethodThe molecular blueprint of targeted radionuclide therapy
Primac, I., Tabury, K., Tasdogan, A., Baatout, S., & Herrmann, K. (2025) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-025-01069-z · Cited by 59 · see citing works
“In patients with metastatic CRPC receiving 177 Lu-PSMA-617, tumour-absorbed doses correlate with reductions in serum PSA levels 296 .”
Bernhardt, P., Svensson, J. B., Hemmingsson, J., van der Meulen, N. P., Zeevaart, J. R., Konijnenberg, M., Müller, C., & Kindblom, J. (2021) · Cancers · doi:10.3390/cancers13092011 · Cited by 55 · see citing works
“3) [177Lu]Lu-PSMA-617 Violet et al [11].”
Radiation Dosimetry in 177Lu-PSMA-617 Therapy
Jackson, P. A., Hofman, M. S., McIntosh, L., Buteau, J. P., & Kumar, A. S. R. (2021) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2021.11.003 · Cited by 55 · see citing works
Self-citationDhiantravan, N., Violet, J. A., Eapen, R. S., Alghazo, O., Scalzo, M., Jackson, P. A., Keam, S. P., Mitchell, C., Neeson, P. J., Sandhu, S. K., et al. (2020) · European Urology Focus · doi:10.1016/j.euf.2020.09.021 · Cited by 54 · see citing works
Self-citationTumor Response to Radiopharmaceutical Therapies: The Knowns and the Unknowns.
Sgouros, G., Dewaraja, Y. K., Escorcia, F. E., Graves, S. A., Hope, T. A., Iravani, A., Pandit-Taskar, N. D., Saboury, B., James, S. S., & ZANZONICO, P. B. (2021) · PubMed Central · doi:10.2967/jnumed.121.262750 · Cited by 54 · see citing works
Self-citationSarnelli, A., Belli, M. L., Iorio, V. D., Mezzenga, E., Celli, M., Severi, S., Tardelli, E., Nicolini, S., Oboldi, D., Uccelli, L., et al. (2019) · Molecules · doi:10.3390/molecules24030621 · Cited by 52 · see citing works
“A reduction in disease burden is obtained after repeated treatment cycles (sometimes even after the first one) in the majority of patients [5,21].”
BackgroundLangbein, T., Kulkarni, H., Schuchardt, C., Müeller, D., Volk, G. F., & Baum, R. P. (2022) · Diagnostics · doi:10.3390/diagnostics12081926 · Cited by 51 · see citing works
“4 Gy/GBq, administering 177LuPSMA-I&T/-617, has been published [14,15,52,53], which translates to an estimated mean absorbed dose of 3.”
BackgroundPandit-Taskar, N. D., Iravani, A., Lee, D., Jacene, H. A., Pryma, D. A., Hope, T. A., Saboury, B., Capala, J., & Wahl, R. L. (2021) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.262977 · Cited by 51 · see citing works
“However, several of these studies were underpowered and did not provide adequate counter evidence to studies in which such relationships were demonstrated (57).”
BackgroundSelf-citationEmerging therapeutic agents for genitourinary cancers
Zarrabi, K. K., Paroya, A., & Wu, S. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0780-z · Cited by 48 · see citing works
“Furthermore, of the 14 patients who did not undergo adequate PSA regression, 9 of them observed a PSA decline greater than 50% after a median of two subsequent cycles [197].”
Wurzer, A. J., Kunert, J.-P., Fischer, S., Felber, V. B., Beck, R., Rose, F. D., D’Alessandria, C., Weber, W., & Wester, H. (2022) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.263371 · Cited by 47 · see citing works
Hong, S., Ferri, V., Duan, H., Aparici, C. M., Davidzon, G., Franc, B. L., Moradi, F., Nguyen, J., Shah, J. C., & Iagaru, A. H. (2023) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-023-06176-6 · Cited by 47 · see citing works
“1 3 SPECT-based post-therapy dosimetries for 177Lu-PSMA617 treatment have shown a trend of dose response in metastatic castration-resistant prostate cancer patients [29, 30].”
MethodWen, X., Xu, P., Zeng, X., Liu, J., Du, C., Zeng, X., Cheng, X., Wang, X., Liang, Y., Zhao, T., et al. (2023) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-023-06229-w · Cited by 47 · see citing works
Establishment of a clinical SPECT/CT protocol for imaging of 161Tb
Marin, I., Rydèn, T., van Essen, M., Svensson, J. B., Gracheva, N., Köster, U., Zeevaart, J. R., van der Meulen, N. P., Müller, C., & Bernhardt, P. (2020) · EJNMMI Physics · doi:10.1186/s40658-020-00314-x · Cited by 48 · see citing works
Radionuclide Therapy in Prostate Cancer: From Standalone to Combination PSMA Theranostics
Sandhu, S. K., Guo, C. W., & Hofman, M. S. (2021) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.243295 · Cited by 47 · see citing works
“01), as well as a strong correlation between the SUVmean of PSMA expression and at least a 50% PSA reduction, although the SUV threshold for optimal PSMA avidity remains to be defined (63).”
BackgroundSelf-citationPrivé, B. M., Derks, Y. H. W., Rosar, F., Franssen, G. M., Peters, S. M. B., Khreish, F., Bartholomä, M. D., Maus, S., Gotthardt, M., Laverman, P., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05661-0 · Cited by 45 · see citing works
Peters, S. M. B., Mink, M. C. T., Privé, B. M., de Bakker, M., de Lange, F., Muselaers, S., Mehra, N., Witjes, J. A., Gotthardt, M., Nagarajah, J., et al. (2023) · EJNMMI Research · doi:10.1186/s13550-023-00952-z · Cited by 48 · see citing works
“Therefore, most [177Lu]Lu-PSMA dosimetry studies performed either used planar scans instead of 3D SPECT [12, 13, 15, 16], acquired only a limited number of imaging time points [10] and/or focused on early time points only [10, 12].”
BackgroundPlouznikoff, N., Artigas, C., Sideris, S., Chanzá, N. M., Gil, T., Peltier, A., & Flamen, P. (2019) · Annals of Nuclear Medicine · doi:10.1007/s12149-019-01404-2 · Cited by 46 · see citing works
Manafi‐Farid, R., Harsini, S., Saidi, B., Ahmadzadehfar, H., Herrmann, K., Briganti, A., Walz, J. C., & Beheshti, M. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05237-y · Cited by 46 · see citing works
Nephrotoxicity after radionuclide therapies
Parihar, A. S., Chopra, S., & Prasad, V. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101295 · Cited by 45 · see citing works
“performed whole-body dosimetry based on MIRD formulations for 177Lu-PSMA-617 RLT by acquiring SPECT/CT images at 4, 24, and 96 hrs post therapy [87].”
MethodSeifert, R., Telli, T., Hadaschik, B. A., Fendler, W. P., Kuo, P. H., & Herrmann, K. (2022) · Journal of Nuclear Medicine · doi:10.2967/jnumed.122.264741 · Cited by 47 · see citing works
Fanti, S., Briganti, A., Emmett, L., Fizazi, K. S., Gillessen, S., Goffin, K. E., Hadaschik, B. A., Herrmann, K., Kunikowska, J., Maurer, T., et al. (2022) · European Urology Oncology · doi:10.1016/j.euo.2022.05.003 · Cited by 44 · see citing works
Self-citationPrivé, B. M., Slootbeek, P. H. J., Laarhuis, B. I., Naga, S. P., van der Doelen, M. J., van Kalmthout, L. W. M., de Keizer, B., Ezziddin, S., Kratochwil, C., Morgenstern, A., et al. (2021) · Prostate Cancer and Prostatic Diseases · doi:10.1038/s41391-021-00424-2 · Cited by 44 · see citing works
Predictors and Real-World Use of Prostate-Specific Radioligand Therapy: PSMA and Beyond
Gafita, A., Marcus, C. V., Kostos, L. K., Schuster, D. M., Calais, J., & Hofman, M. S. (2022) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_350946 · Cited by 44 · see citing works
Self-citationVlachostergios, P. J., Niaz, M. J., Sun, M., Mosallaie, S. A., Thomas, C., Christos, P. J., Osborne, J. R., Molina, A. M., Nanus, D. M., Bander, N. H., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.630589 · Cited by 43 · see citing works
“This study was limited by the retrospective analysis of prospectively enrolled patients, the uncertainty for cut-offs that may potentially define different levels of PSMA expression, and the use of two different imaging modalities with different detection sensitivities (39).”
MethodSafety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals
Ladrière, T., Faudemer, J., Levigoureux, E., Peyronnet, D., Desmonts, C., & Vigne, J. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041240 · Cited by 46 · see citing works
Giraudet, A., Kryza, D., Hofman, M. S., Moreau, A., Fizazi, K. S., Fléchon, A., Hicks, R. J., & Tran, B. (2021) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359211053898 · Cited by 43 · see citing works
Self-citationRole of Artificial Intelligence in Theranostics
Brosch-Lenz, J., Yousefirizi, F., Zukotynski, K., Beauregard, J.-M., Gaudet, V., Saboury, B., Rahmim, A., & Uribe, C. (2021) · PET Clinics · doi:10.1016/j.cpet.2021.06.002 · Cited by 42 · see citing works
Khreish, F., Kochems, N., Rosar, F., Sabet, A., Ries, M., Maus, S., Saar, M., Bartholomä, M. D., & Ezziddin, S. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-04828-5 · Cited by 41 · see citing works
“Despite this significant correlation, the authors were unable to determine a mean SUV below which patients were unlikely to respond [26].”
BackgroundInfluentialDosimetry for Optimized, Personalized Radiopharmaceutical Therapy
Graves, S. A., & Hobbs, R. F. (2020) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2020.07.008 · Cited by 40 · see citing works
Plichta, K. A., Graves, S. A., & Buatti, J. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212095 · Cited by 39 · see citing works
“Early studies investigating the relationship between tumor radiation absorbed dose from 177Lu-PSMA therapy and treatment response have demonstrated an increased likelihood of response with increasing dose to tumors [59,60].”
BackgroundMaekawa, S., Takata, R., & Obara, W. (2024) · Cancers · doi:10.3390/cancers16030523 · Cited by 44 · see citing works
“…their diagnostic accuracy does not differ significantly [260–262 , Radiation therapy utilizing the labeling of PSMA ligands to target PSMA-positive cells and the surrounding microenvironment involves both alpha and beta radionuclides such as 225 Ac-PSMA and 177 Lu-PSMA, respectively [255,271–273].”
Backgroundvon Eyben, F. E., Bauman, G. S., von Eyben, R., Rahbar, K., Soydal, Ç., Haug, A. R., Virgolini, I. J., Kulkarni, H., Baum, R. P., & Paganelli, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239054 · Cited by 40 · see citing works
“PSMA PET/CT resulted in a better staging of patients with PC than conventional imaging such as bone and CT scans [50,51].”
BackgroundMethodChi, K. N., Armstrong, A. J., Krause, B. J., Herrmann, K., Rahbar, K., de Bono, J. S., Adra, N., Garje, R., Michalski, J. M., Kempel, M. M., et al. (2024) · European Urology · doi:10.1016/j.eururo.2023.12.004 · Cited by 37 · see citing works
Potluri, H. K., Ferreira, C. A., Grudzinski, J. J., Massey, C. F., Aluicio‐Sarduy, E., Engle, J. W., Kwon, O., Marsh, I. R., Bednarz, B. P., Hernandez, R. T., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005060 · Cited by 38 · see citing works
Quantitative 177Lu SPECT/CT imaging for personalized dosimetry using a ring-shaped CZT-based camera
Danieli, R., Stella, M., Leube, J., Tran‐Gia, J., Marin, C., Uribe, C., Vanderlinden, B., Reynaert, N., Flamen, P., & Levillain, H. (2023) · EJNMMI Physics · doi:10.1186/s40658-023-00586-z · Cited by 38 · see citing works
Kind, F., Michalski, K., Yousefzadeh‐Nowshahr, E., Meyer, P. T., Mix, M. D., & Ruf, J. (2022) · EJNMMI Research · doi:10.1186/s13550-022-00891-1 · Cited by 37 · see citing works
“[29], imaging-based bone marrow dosimetry may be limited as well, as in case of diffuse metastases dosages can be overestimated.”
Background
- 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 › Pulmonary and Respiratory Medicine › 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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