Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 13/2015

01.12.2015 | Original Article

Pre-therapeutic dosimetry of normal organs and tissues of 177Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

verfasst von: Levent Kabasakal, Mohammad AbuQbeitah, Aslan Aygün, Nami Yeyin, Meltem Ocak, Emre Demirci, Turkay Toklu

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 13/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

177Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of 177Lu-labeled PSMA ligand.

Methods

The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected 177Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations.

Results

The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq.

Conclusion

Our first results suggested that 177Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are within acceptable ranges; however, there is a substantial individual variance so patient dosimetry seems to be mandatory.
Literatur
1.
Zurück zum Zitat Wright GL, 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.CrossRefPubMed Wright GL, 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.CrossRefPubMed
2.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
3.
Zurück zum Zitat Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997;3:81–5.PubMed Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997;3:81–5.PubMed
4.
Zurück zum Zitat Eder M, Schäfer M, Bauder-Wüst U, Hull W-E, Wängler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 2012;23:688–97. Eder M, Schäfer M, Bauder-Wüst U, Hull W-E, Wängler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 2012;23:688–97.
5.
Zurück zum Zitat Eder M, Schäfer M, Bauder-Wüst U, Haberkorn U, Eisenhut M, Kopka K. Preclinical evaluation of a bispecific low-molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer. Prostate 2014;74:659–68.CrossRefPubMed Eder M, Schäfer M, Bauder-Wüst U, Haberkorn U, Eisenhut M, Kopka K. Preclinical evaluation of a bispecific low-molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer. Prostate 2014;74:659–68.CrossRefPubMed
6.
Zurück zum Zitat Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga]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. Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga]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.
7.
Zurück zum Zitat 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. 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.
8.
Zurück zum Zitat Kabasakal L, Demirci E, Ocak M, Akyel R, Nematyazar J, Aygun A, et al. Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging. Nucl Med Commun 2015;36:582–7. Kabasakal L, Demirci E, Ocak M, Akyel R, Nematyazar J, Aygun A, et al. Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging. Nucl Med Commun 2015;36:582–7.
9.
Zurück zum Zitat Kratochwil C, Giesel FL, Eder M, Afshar-Oromieh A, Benešová M, Mier W, et al. [(177)Lu]Lutetium-labelled PSMA ligand-induced remission in a patient with metastatic prostate cancer. Eur J Nucl Med Mol Imaging 2015;42:987–8. Kratochwil C, Giesel FL, Eder M, Afshar-Oromieh A, Benešová M, Mier W, et al. [(177)Lu]Lutetium-labelled PSMA ligand-induced remission in a patient with metastatic prostate cancer. Eur J Nucl Med Mol Imaging 2015;42:987–8.
10.
Zurück zum Zitat Benešová M, Schäfer M, Bauder-Wüst U, Afshar-Oromieh A, Kratochwil C, Mier W, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 2015;56:914–20. Benešová M, Schäfer M, Bauder-Wüst U, Afshar-Oromieh A, Kratochwil C, Mier W, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 2015;56:914–20.
11.
Zurück zum Zitat Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med 1999;40:37S–61S.PubMed Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med 1999;40:37S–61S.PubMed
12.
Zurück zum Zitat Brown S, Bailey DL, Willowson K, Baldock C. Investigation of the relationship between linear attenuation coefficients and CT Hounsfield units using radionuclides for SPECT. Appl Radiat Isot 2008;66:1206–12.CrossRefPubMed Brown S, Bailey DL, Willowson K, Baldock C. Investigation of the relationship between linear attenuation coefficients and CT Hounsfield units using radionuclides for SPECT. Appl Radiat Isot 2008;66:1206–12.CrossRefPubMed
13.
Zurück zum Zitat Wessels BW, Bolch WE, Bouchet LG, Breitz HB, Denardo GL, Meredith RF, et al. Bone marrow dosimetry using blood-based models for radiolabeled antibody therapy: a multiinstitutional comparison. J Nucl Med 2004;45:1725–33. Wessels BW, Bolch WE, Bouchet LG, Breitz HB, Denardo GL, Meredith RF, et al. Bone marrow dosimetry using blood-based models for radiolabeled antibody therapy: a multiinstitutional comparison. J Nucl Med 2004;45:1725–33.
14.
Zurück zum Zitat Thierens HM, Monsieurs MA, Bacher K. Patient dosimetry in radionuclide therapy: the whys and the wherefores. Nucl Med Commun 2005;26:593–9.CrossRefPubMed Thierens HM, Monsieurs MA, Bacher K. Patient dosimetry in radionuclide therapy: the whys and the wherefores. Nucl Med Commun 2005;26:593–9.CrossRefPubMed
15.
Zurück zum Zitat Glatting G, Bardiès M, Lassmann M. Treatment planning in molecular radiotherapy. Z Med Phys 2013;23:262–9. Glatting G, Bardiès M, Lassmann M. Treatment planning in molecular radiotherapy. Z Med Phys 2013;23:262–9.
16.
Zurück zum Zitat Wehrmann C, Senftleben S, Zachert C, Müller D, Baum RP. Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC. Cancer Biother Radiopharm 2007;22:406–16. Wehrmann C, Senftleben S, Zachert C, Müller D, Baum RP. Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC. Cancer Biother Radiopharm 2007;22:406–16.
17.
Zurück zum Zitat Kwekkeboom D, Bakker W, Kooij P, Konijnenberg M, Srinivasan A, Erion J, et al. [177 Lu-DOTA0,Tyr3]octreotate: comparison with [111In-DTPA0]octreotide in patients. Eur J Nucl Med 2001;28:1319–25. Kwekkeboom D, Bakker W, Kooij P, Konijnenberg M, Srinivasan A, Erion J, et al. [177 Lu-DOTA0,Tyr3]octreotate: comparison with [111In-DTPA0]octreotide in patients. Eur J Nucl Med 2001;28:1319–25.
18.
Zurück zum Zitat Forrer F, Krenning EP, Kooij PP, Bernard BF, Konijnenberg M, Bakker WH, et al. Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA(0),Tyr(3)]octreotate. Eur J Nucl Med Mol Imaging 2009;36:1138–46.PubMedCentralCrossRefPubMed Forrer F, Krenning EP, Kooij PP, Bernard BF, Konijnenberg M, Bakker WH, et al. Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA(0),Tyr(3)]octreotate. Eur J Nucl Med Mol Imaging 2009;36:1138–46.PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat Svensson J, Berg G, Wängberg B, Larsson M, Forssell-Aronsson E, Bernhardt P. Renal function affects absorbed dose to the kidneys and haematological toxicity during 177Lu-DOTATATE treatment. Eur J Nucl Med Mol Imaging 2015;42:947–55.. Svensson J, Berg G, Wängberg B, Larsson M, Forssell-Aronsson E, Bernhardt P. Renal function affects absorbed dose to the kidneys and haematological toxicity during 177Lu-DOTATATE treatment. Eur J Nucl Med Mol Imaging 2015;42:947–55..
20.
Zurück zum Zitat Sandström M, Garske U, Granberg D, Sundin A, Lundqvist H. Individualized dosimetry in patients undergoing therapy with (177)Lu-DOTA-D-Phe(1)-Tyr(3)-octreotate. Eur J Nucl Med Mol Imaging 2010;37:212–25.CrossRefPubMed Sandström M, Garske U, Granberg D, Sundin A, Lundqvist H. Individualized dosimetry in patients undergoing therapy with (177)Lu-DOTA-D-Phe(1)-Tyr(3)-octreotate. Eur J Nucl Med Mol Imaging 2010;37:212–25.CrossRefPubMed
21.
Zurück zum Zitat Van Essen M, Krenning EP, Kam BLR, de Jong M, Valkema R, Kwekkeboom DJ. Peptide-receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol 2009;5:382–93. Van Essen M, Krenning EP, Kam BLR, de Jong M, Valkema R, Kwekkeboom DJ. Peptide-receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol 2009;5:382–93.
22.
Zurück zum Zitat Sandström M, Garske-Román U, Granberg D, Johansson S, Widström C, Eriksson B, et al. Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment. J Nucl Med 2013;54:33–41. Sandström M, Garske-Román U, Granberg D, Johansson S, Widström C, Eriksson B, et al. Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment. J Nucl Med 2013;54:33–41.
23.
Zurück zum Zitat Lassmann M, Chiesa C, Flux G, Bardiès M, EANM Dosimetry Committee. EANM Dosimetry Committee guidance document: good practice of clinical dosimetry reporting. Eur J Nucl Med Mol Imaging 2011;38:192–200. Lassmann M, Chiesa C, Flux G, Bardiès M, EANM Dosimetry Committee. EANM Dosimetry Committee guidance document: good practice of clinical dosimetry reporting. Eur J Nucl Med Mol Imaging 2011;38:192–200.
24.
Zurück zum Zitat Deasy JO, Moiseenko V, Marks L, Chao KSC, Nam J, Eisbruch A. Radiotherapy dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys 2010;76:S58–63.PubMedCentralCrossRefPubMed Deasy JO, Moiseenko V, Marks L, Chao KSC, Nam J, Eisbruch A. Radiotherapy dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys 2010;76:S58–63.PubMedCentralCrossRefPubMed
25.
Zurück zum Zitat Grundmann O, Mitchell GC, Limesand KH. Sensitivity of salivary glands to radiation: from animal models to therapies. J Dent Res 2009;88:894–903.PubMedCentralCrossRefPubMed Grundmann O, Mitchell GC, Limesand KH. Sensitivity of salivary glands to radiation: from animal models to therapies. J Dent Res 2009;88:894–903.PubMedCentralCrossRefPubMed
26.
Zurück zum Zitat Li Y, Taylor JMG, Ten Haken RK, Eisbruch A. The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy. Int J Radiat Oncol Biol Phys 2007;67:660–9.PubMedCentralCrossRefPubMed Li Y, Taylor JMG, Ten Haken RK, Eisbruch A. The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy. Int J Radiat Oncol Biol Phys 2007;67:660–9.PubMedCentralCrossRefPubMed
27.
Zurück zum Zitat Jeong SY, Kim HW, Lee S-W, Ahn B-C, Lee J. Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms. Thyroid 2013;23:609–16. Jeong SY, Kim HW, Lee S-W, Ahn B-C, Lee J. Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms. Thyroid 2013;23:609–16.
28.
Zurück zum Zitat Grewal RK, Larson SM, Pentlow CE, Pentlow KS, Gonen M, Qualey R, et al. Salivary gland side effects commonly develop several weeks after initial radioactive iodine ablation. J Nucl Med 2009;50:1605–10.CrossRefPubMed Grewal RK, Larson SM, Pentlow CE, Pentlow KS, Gonen M, Qualey R, et al. Salivary gland side effects commonly develop several weeks after initial radioactive iodine ablation. J Nucl Med 2009;50:1605–10.CrossRefPubMed
29.
Zurück zum Zitat Sreebny LM, Valdini A, Yu A. Xerostomia. Part II: relationship to nonoral symptoms, drugs, and diseases. Oral Surg Oral Med Oral Pathol 1989;68:419–27.CrossRefPubMed Sreebny LM, Valdini A, Yu A. Xerostomia. Part II: relationship to nonoral symptoms, drugs, and diseases. Oral Surg Oral Med Oral Pathol 1989;68:419–27.CrossRefPubMed
30.
Zurück zum Zitat Norrgren K, Svegborn SL, Areberg J, Mattsson S. Accuracy of the quantification of organ activity from planar gamma camera images. Cancer Biother Radiopharm 2003;18:125–31.CrossRefPubMed Norrgren K, Svegborn SL, Areberg J, Mattsson S. Accuracy of the quantification of organ activity from planar gamma camera images. Cancer Biother Radiopharm 2003;18:125–31.CrossRefPubMed
31.
Zurück zum Zitat Garkavij M, Nickel M, Sjögreen-Gleisner K, Ljungberg M, Ohlsson T, Wingårdh K, et al. 177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: analysis of dosimetry with impact on future therapeutic strategy. Cancer 2010;116:1084–92. Garkavij M, Nickel M, Sjögreen-Gleisner K, Ljungberg M, Ohlsson T, Wingårdh K, et al. 177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: analysis of dosimetry with impact on future therapeutic strategy. Cancer 2010;116:1084–92.
32.
Zurück zum Zitat Kletting P, Müller B, Erentok B, Schmaljohann J, Behrendt FF, Reske SN, et al. Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy. Med Phys 2012;39:5708–17. Kletting P, Müller B, Erentok B, Schmaljohann J, Behrendt FF, Reske SN, et al. Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy. Med Phys 2012;39:5708–17.
33.
Zurück zum Zitat Hindorf C, Glatting G, Chiesa C, Lindén O, Flux G, EANM Dosimetry Committee. EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry. Eur J Nucl Med Mol Imaging 2010;37:1238–50. Hindorf C, Glatting G, Chiesa C, Lindén O, Flux G, EANM Dosimetry Committee. EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry. Eur J Nucl Med Mol Imaging 2010;37:1238–50.
Metadaten
Titel
Pre-therapeutic dosimetry of normal organs and tissues of 177Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer
verfasst von
Levent Kabasakal
Mohammad AbuQbeitah
Aslan Aygün
Nami Yeyin
Meltem Ocak
Emre Demirci
Turkay Toklu
Publikationsdatum
01.12.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 13/2015
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-015-3125-3

Weitere Artikel der Ausgabe 13/2015

European Journal of Nuclear Medicine and Molecular Imaging 13/2015 Zur Ausgabe