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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 2/2022

Open Access 01-01-2022 | Prostate Cancer | Original Article

Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome

Authors: Steffie M. B. Peters, Bastiaan M. Privé, Maarten de Bakker, Frank de Lange, Walter Jentzen, Annemarie Eek, Constantijn H. J. Muselaers, Niven Mehra, J. Alfred Witjes, Martin Gotthardt, James Nagarajah, Mark W. Konijnenberg

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2022

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Abstract

Introduction

While [177Lu]Lu-PSMA radioligand therapy is currently only applied in end-stage metastatic castrate-resistant prostate cancer (mCRPC) patients, also low-volume hormone-sensitive metastatic prostate cancer (mHSPC) patients can benefit from it. However, there are toxicity concerns related to the sink effect in low-volume disease. This prospective study aims to determine the kinetics of [177Lu]Lu-PSMA in mHSPC patients, analyzing the doses to organs at risk (salivary glands, kidneys, liver, and bone marrow) and tumor lesions < 1 cm diameter.

Methods

Ten mHSPC patients underwent two cycles of [177Lu]Lu-PSMA therapy. Three-bed position SPECT/CT was performed at 5 time points after each therapy. Organ dosimetry and lesion dosimetry were performed using commercial software and a manual approach, respectively. Correlation between absorbed index lesion dose and treatment response (PSA drop of > 50% at the end of the study) was calculated and given as Spearman’s r and p-values.

Results

Kinetics of [177Lu]Lu-PSMA in mHSPC patients are comparable to those in mCRPC patients. Lesion absorbed dose was high (3.25 ± 3.19 Gy/GBq) compared to organ absorbed dose (salivary glands: 0.39 ± 0.17 Gy/GBq, kidneys: 0.49 ± 0.11 Gy/GBq, liver: 0.09 ± 0.01 Gy/GBq, bone marrow: 0.017 ± 0.008 Gy/GBq). A statistically significant correlation was found between treatment response and absorbed index lesion dose (p = 0.047).

Conclusions

We successfully performed small lesion dosimetry and showed that the tumor sink effect in mHSPC patients is of less concern than was expected. Tumor-to-organ ratio of absorbed dose was high and tumor uptake correlates with PSA response. Additional treatment cycles are legitimate in terms of organ toxicity and could lead to better tumor response.
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Literature
1.
Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med. 2012;366:981–90.PubMedPubMedCentralCrossRef
2.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.PubMedCrossRef
3.
Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017;71:630–42.PubMedCrossRef
4.
James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, et al. Survival with newly diagnosed metastatic prostate cancer in the “docetaxel era”: data from 917 patients in the control arm of the STAMPEDE trial (MRC PR08, CRUK/06/019). Eur Urol. 2015;67:1028–38.PubMedCrossRef
5.
Wright GL Jr, Haley C, Beckett ML, Schellhammer PF. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1:18–28.PubMedCrossRef
6.
Perner S, Hofer MD, Kim R, Shah RB, Li H, Möller P, et al. Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol. 2007;38:696–701.PubMedCrossRef
7.
Silver DA, Pellicer I, Fair WR, Heston W, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3:81–5.PubMed
8.
Privé BM, Israël B, Schilham MG, Muselaers CH, Zámecnik P, Mulders PF, et al. Evaluating F-18-PSMA-1007-PET in primary prostate cancer and comparing it to multi-parametric MRI and histopathology. Prostate Cancer Prostatic Dis. 2020: 1–8.
9.
Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the 68 Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209.PubMedCrossRef
10.
Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of 68gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195:1436–43.PubMedCrossRef
11.
Giesel FL, Knorr K, Spohn F, Will L, Maurer T, Flechsig P, et al. Detection efficacy of 18F-PSMA-1007 PET/CT in 251 patients with biochemical recurrence of prostate cancer after radical prostatectomy. J Nucl Med. 2019;60:362–8.PubMedPubMedCentralCrossRef
12.
Kesch C, Kratochwil C, Mier W, Kopka K, Giesel FL. 68Ga or 18F for prostate cancer imaging? J Nucl Med. 2017;58:687–8.PubMedCrossRef
13.
Pandit-Taskar N, O’Donoghue JA, Ruan S, Lyashchenko SK, Carrasquillo JA, Heller G, et al. First-in-human imaging with 89Zr-Df-IAB2M anti-PSMA minibody in patients with metastatic prostate cancer: pharmacokinetics, biodistribution, dosimetry, and lesion uptake. J Nucl Med. 2016;57:1858–64.PubMedPubMedCentralCrossRef
14.
Zechmann CM, Afshar-Oromieh A, Armor T, Stubbs JB, Mier W, Hadaschik B, et al. Radiation dosimetry and first therapy results with a 124 I/131 I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014;41:1280–92.PubMedPubMedCentralCrossRef
15.
Ahmadzadehfar H, Eppard E, Kürpig S, Fimmers R, Yordanova A, Schlenkhoff CD, et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget. 2016;7:12477.PubMedPubMedCentralCrossRef
16.
Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. Lutetium-177 PSMA radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57(7):1006–13.
17.
Heck MM, Tauber R, Schwaiger S, Retz M, D’Alessandria C, Maurer T, et al. Treatment outcome, toxicity, and predictive factors for radioligand therapy with 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. Eur Urol. 2019;75:920–6.PubMedCrossRef
18.
Tagawa ST, Milowsky MI, Morris M, Vallabhajosula S, Christos P, Akhtar NH, et al. Phase II study of lutetium-177–labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res. 2013;19:5182–91.PubMedPubMedCentralCrossRef
19.
Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schäfers M, Essler M, et al. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. J Nucl Med. 2017;58:85–90.PubMedCrossRef
20.
Kratochwil C, Giesel FL, Stefanova M, Benesova M, Bronzel M, Afshar-Oromieh A, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with Lu-177 labeled PSMA-617. J Nucl Med. 2016;57:1170–6.PubMedCrossRef
21.
Hofman MS, Emmett L, Sandhu SK, Iravani A, Joshua AM, Goh JC, et al. TheraP: a randomised phase II trial of 177Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration resistant prostate cancer (mCRPC) progressing after docetaxel: initial results (ANZUP protocol 1603). J Clin Oncol. 2020;38:5500.CrossRef
22.
Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33.PubMedCrossRef
23.
Violet JA, Jackson P, Ferdinandus J, Sandhu S, Akhurst T, Iravani A, et al. Dosimetry of Lu-177 PSMA-617 in metastatic castration-resistant prostate cancer: correlations between pre-therapeutic imaging and “whole body” tumor dosimetry with treatment outcomes. J Nucl Med. 2019;60:517–23.PubMedCrossRef
24.
Okamoto S, Thieme A, Allmann J, D’Alessandria C, Maurer T, Retz M, et al. Radiation dosimetry for 177Lu-PSMA I&T in metastatic castration-resistant prostate cancer: absorbed dose in normal organs and tumor lesions. J Nucl Med. 2017;58:445–50.PubMedCrossRef
25.
Delker A, Fendler WP, Kratochwil C, Brunegraf A, Gosewisch A, Gildehaus FJ, et al. Dosimetry for 177 Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:42–51.PubMedCrossRef
26.
Kabasakal L, AbuQbeitah M, Aygün A, Yeyin N, Ocak M, Demirci E, et al. Pre-therapeutic dosimetry of normal organs and tissues of 177 Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:1976–83.PubMedCrossRef
27.
Privé BM, Peters SMB, Muselaers CH, van Oort IM, Janssen MJ, Sedelaar M, et al. Lutetium-177-PSMA-617 in low-volume hormone sensitive metastatic prostate cancer, a prospective pilot study. Clin Cancer Res. 2021.
28.
Beauregard J-M, Hofman MS, Kong G, Hicks RJ. The tumour sink effect on the biodistribution of 68 Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2012;39:50–6.PubMedCrossRef
29.
Gaertner FC, Halabi K, Ahmadzadehfar H, Kürpig S, Eppard E, Kotsikopoulos C, et al. Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. Oncotarget. 2017;8:55094.PubMedPubMedCentralCrossRef
30.
Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart H, Hadaschik B, et al. PET imaging with a [68 Ga] gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40:486–95.PubMedCrossRef
31.
Dutch Society of Nuclear Medicine. Procedure guidelines nuclear medicine. Part IV: Equipment. Kloosterhof Neer BV; 2016. p. 662–70.
32.
Peters SM, Viol SLM, van der Werf NR, de Jong N, van Velden FH, Meeuwis A, et al. Variability in lutetium-177 SPECT quantification between different state-of-the-art SPECT/CT systems. EJNMMI physics. 2020;7:1–13.CrossRef
33.
Ljungberg M, Celler A, Konijnenberg MW, Eckerman KF, Dewaraja YK, Sjogreen-Gleisner K. MIRD pamphlet no. 26: joint EANM/MIRD guidelines for quantitative 177Lu SPECT applied for dosimetry of radiopharmaceutical therapy. J Nucl Med. 2016;57:151–62.PubMedCrossRef
34.
Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD pamphlet no. 21: a generalized schema for radiopharmaceutical dosimetry—standardization of nomenclature. J Nucl Med. 2009;50:477–84.PubMedCrossRef
35.
Valentin J. Basic anatomical and physiological data for use in radiological protection: reference values: ICRP Publication 89. Ann ICRP. 2002;32:1–277.CrossRef
36.
Hindorf C, Glatting G, Chiesa C, Lindén O, Flux G. EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry. Eur J Nucl Med Mol Imaging. 2010;37:1238–50.PubMedCrossRef
37.
Buijs WC, Siegel JA, Boerman OC, Corstens FH. Absolute organ activity estimated by five different methods of background correction. J Nucl Med. 1998;39:2167–72.PubMed
38.
Jentzen W. An improved iterative thresholding method to delineate PET volumes using the delineation-averaged signal instead of the enclosed maximum signal. J Nucl Med Technol. 2015;43:28–35.PubMedCrossRef
39.
Andersson M, Johansson L, Minarik D, Mattsson S, Leide-Svegborn S. An internal radiation dosimetry computer program, IDAC 2.0, for estimation of patient doses from radiopharmaceuticals. Radiat Prot Dosimetry. 2014;162:299–305.PubMedCrossRef
40.
Gear JI, Cox MG, Gustafsson J, Gleisner KS, Murray I, Glatting G, et al. EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations. Eur J Nucl Med Mol Imaging. 2018;45:2456–74.PubMedPubMedCentralCrossRef
41.
Begum NJ, Thieme A, Eberhardt N, Tauber R, D’Alessandria C, Beer AJ, et al. The effect of total tumor volume on the biologically effective dose to tumor and kidneys for 177Lu-labeled PSMA peptides. J Nucl Med. 2018;59:929–33.PubMedCrossRef
42.
Deasy JO, Moiseenko V, Marks L, Chao KC, Nam J, Eisbruch A. Radiotherapy dose–volume effects on salivary gland function. Int J Radiat Oncol Biol Phys. 2010;76:S58–63.PubMedPubMedCentralCrossRef
43.
Stewart F, Akleyev A, Hauer-Jensen M, Hendry J, Kleiman N, Macvittie T, et al. ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs–threshold doses for tissue reactions in a radiation protection context. Ann ICRP. 2012;41:1–322.PubMedCrossRef
44.
Bergsma H, Konijnenberg MW, Van Der Zwan WA, Kam BL, Teunissen JJ, Kooij PP, et al. Nephrotoxicity after PRRT with 177 Lu-DOTA-octreotate. Eur J Nucl Med Mol Imaging. 2016;43:1802–11.PubMedPubMedCentralCrossRef
45.
Wessels BW, Konijnenberg MW, Dale RG, Breitz HB, Cremonesi M, Meredith RF, et al. MIRD pamphlet No. 20: the effect of model assumptions on kidney dosimetry and response—implications for radionuclide therapy. J Nucl Med. 2008;49:1884–99.
46.
Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JMC, Papaemmanuil E, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520:353–7.PubMedPubMedCentralCrossRef
47.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883–92.PubMedPubMedCentralCrossRef
48.
49.
Hänscheid H, Lapa C, Buck AK, Lassmann M, Werner RA. Dose mapping after endoradiotherapy with 177Lu-DOTATATE/DOTATOC by a single measurement after 4 days. J Nucl Med. 2018;59:75–81.PubMedCrossRef
50.
Edler von Eyben F, Singh A, Zhang J, Nipsch K, Meyrick D, Lenzo N, et al. (177)Lu-PSMA radioligand therapy of predominant lymph node metastatic prostate cancer. Oncotarget. 2019;10:2451–61.CrossRef
51.
Del Prete M, Buteau F-A, Arsenault F, Saighi N, Bouchard L-O, Beaulieu A, et al. Personalized 177 Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial. Eur J Nucl Med Mol Imaging. 2019;46:728–42.PubMedCrossRef
Metadata
Title
Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome
Authors
Steffie M. B. Peters
Bastiaan M. Privé
Maarten de Bakker
Frank de Lange
Walter Jentzen
Annemarie Eek
Constantijn H. J. Muselaers
Niven Mehra
J. Alfred Witjes
Martin Gotthardt
James Nagarajah
Mark W. Konijnenberg
Publication date
01-01-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-021-05471-4

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