Top

Published in:

01-06-2016 | Research Article

Lacrimal Glands May Represent Organs at Risk for Radionuclide Therapy of Prostate Cancer with [¹⁷⁷Lu]DKFZ-PSMA-617

Authors: Melanie Hohberg, Wolfgang Eschner, Matthias Schmidt, Markus Dietlein, Carsten Kobe, Thomas Fischer, Alexander Drzezga, Markus Wild

Published in: Molecular Imaging and Biology | Issue 3/2016

Abstract

Purpose

Calculating the absorbed dose is important for the determination of risk and therapeutic benefit of internal radiation therapy. The aim of this study was to perform image-based absorbed dose calculation for critical organs during the first cycle of [¹⁷⁷Lu]DKFZ-PSMA-617 therapy in a small cohort of patients with metastatic prostate cancer.

Procedures

Nine patients with a history of prostate cancer documented by histopathology and radiologic evidence of metastatic diseases underwent radioligand therapy with [¹⁷⁷Lu]DKFZ-PSMA-617. Conjugated planar whole-body scintigraphies acquired at 0.5, 24, 48, 72, and 168 h post-injection were analyzed by regions of interest, and time-activity curves were generated for various organs. Cumulated activities and residence times were calculated by bi-exponential fit of the time-activity curves. Mean absorbed doses were finally estimated using OLINDA/EXM1.1™. Additionally, the uncertainty when omitting the last measurement (168 h p.i.) was studied.

Results

The following mean absorbed doses were calculated: 2.82 mGy/MBq for the lacrimal glands, 0.72 mGy/MBq for the salivary glands, 0.53 mGy/MBq for the kidneys, and 0.42 mGy/MBq for the nasal mucous membrane. Omitting the last measurement resulted in a mean deviation of 10 to 25 % for absorbed dose values as compared to the ones received by analyzing all measurements.

Conclusion

Absorbed organ doses of [¹⁷⁷Lu]DKFZ-PSMA-617 therapy are not likely to be critical for kidneys, salivary glands, and the nasal mucous membrane. The lacrimal glands may represent the dose-limiting organs. Whole-body scintigraphy appears sufficient for dose estimation, but late measurements are mandatory, if accurate dose calculation is required.

Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386CrossRefPubMed

Zechmann CM, Afashar-Oromieh A, Armor T et al (2014) 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 41:1280–1292CrossRefPubMedPubMedCentral

Bacich DJ, Pinto JT, Tong WP, Heston WD (2001) Cloning expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase. Mamm Genome 12:117–123CrossRefPubMed

Perner S, Hofer MD, Kim R et al (2007) Prostate-specific membrane antigen expression as a predictor of prostate cancer. Hum Pathol 38:696–701CrossRefPubMed

Bradford TJ, Tomlins SA, Wang X, Chinnaiyan AM (2006) Molecular markers of prostate cancer. Urol Oncol 24:538–551CrossRefPubMed

Bander NH, Milowsky MI, Nanus DM et al (2005) Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. J Clin Oncol 23:4591–4601CrossRefPubMed

Foss CA, Mease RC, Fan H et al (2005) Radiolabeled small-molecule ligands for prostate-specific membrane antigen: in vivo imaging in experimental models of prostate cancer. Clin Cancer Res 11:4022–4028CrossRefPubMed

Humblet V, Lapidus R, Williams LR et al (2005) High-affinity near-infrared fluorescent small-molecule contrast agents for in vivo imaging of prostate-specific membrane antigen. Mol Imaging 4:448–462PubMed

Pomper MG, Musachio JL, Zhang J et al (2002) 11C-MCG: synthesis, uptake selectivity, and primate PET of a probe for glutamate carboxypeptidase II (NAALADase). Mol Imaging 1:96–101CrossRefPubMed

10.

Eder M, Schafer M, Bauder-Wust U et al (2012) 68Ga-complex lipophilicity and targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 23:688–697CrossRefPubMed

11.

Afshar-Oromieh A, Haberkorn U, Hadaschik B et al (2013) PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer. Eur J Nucl Med Mol Imaging 40:1629–1630CrossRefPubMed

12.

Eiber M, Nekolla SG, Maurer T et al (2014) Ga-PSMA PET/MR with multimodality image analysis for primary prostate cancer. Abdom Imaging 40:1769–1771CrossRef

13.

Tasch J, Gong M, Sadelain M, Heston WD (2001) A unique folate hydrolase, prostate-specific membrane antigen (PSMA): a target for immunotherapy? Crit Rev Immunol 21:249–261CrossRefPubMed

14.

Kratochwil C, Giesel FL, Eder M et al (2015) [¹⁷⁷Lu]Lutetium-labelled PSMA ligand-induced remission in a patient with metastatic prostate cancer. Eur J Nucl Med Mol Imaging 42:987–988CrossRefPubMed

15.

Bé MM, Chisté V, Dulie C, et al (2004) Table of radionuclides (Vol. 2-A = 151 to 242). Bureau international des poids et mesures, Pavillon de Breteuil, Sèvres

16.

Hindorf C, Glatting G, Chiesa C, Lindén O et al (2010) EANM dosimetry committee guidelines for bone marrow and whole-body dosimetry. Eur J Med Mol Imgaging 37:1238–1250CrossRef

17.

Stabin MG, Sparks RB, Crowe E (2005) OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 46:1023–1027PubMed

18.

Snyder WS, Fischer HL Jr, Ford MR, Warner GG (1969) Estimate of absorbed fractions for monoenergetic photon sources uniformly distributed in various organs of a heterogeneous phantom. MIRD pamphlet no. 5. J Nucl Med 10:7–52

19.

Loevinger R, Budinger TF, Watson EE (1988) MIRD primer for absorbed dose calculations. Society of Nuclear Medicine, New York

20.

Snyder WS, Cook MJ, Nasset ES, et al (1979) Report of the task group on reference man. ICRP Publication 23

21.

Bukhari AA, Basheer NA, Joharjy HI (2014) Age, gender and interracial variability of normal lacrimal gland volume using MRI. Ophthal Plast Reconstr Surg 30:388–391CrossRefPubMed

22.

Bingham CM, Castro A, Realini T et al (2013) Calculated CT volumes of lacrimal glands in normal Caucasian orbits. Ophthal Plast Reconstr Surg 29:157–159CrossRefPubMed

23.

Garkavij M, Nickel M, Sjögreen-Gleisner K et al (2010) 177Lu-[DOTA0, Tyr3] Octreotate therapy in patients with disseminated neuroendocrine tumors: analysis of dosimetry with impact on future therapeutic strategy. Cancer 116:1084–1092CrossRefPubMed

24.

Sandström M, Garske U, Granberg D et al (2010) Individualized dosimetry in patients undergoing therapy with 177Lu-DOTA-D-Phe1-Tyr3-octreotate. Eur J Nucl Med Mol Imaging 37:212–225CrossRefPubMed

25.

Delker A, Fendler WP, Kratochwil C et al (2016) Dosimetry for 177Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging 43:42–51CrossRefPubMed

26.

Weineisen M, Schottelius M, Simecek J et al (2015) 68Ga- and 177Lu-labeled PSMA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med 56:1169–1176CrossRefPubMed

27.

Pandit-Taskar N, O’Donoghue JA, Durack JC et al (2015) A phase I/II study for analytic validation of 89Zr-J591 immunoPET as a molecular imaging agent for metastatic prostate cancer. Clin Cancer Res 21:5277–5285CrossRefPubMed

28.

Banerjee SR, Foss CA, Castanares M et al (2008) Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA). J Med Chem 51:4504–4517CrossRefPubMedPubMedCentral

29.

Maurer T, Weirich G, Schottelius M et al (2015) Prostate-specific membrane antigen-radioguided surgery for metastatic lymph nodes in prostate cancer. Eur Urol 68:530–534CrossRefPubMed

30.

Benesova M, Schafer M, Bauder-Wust U et al (2015) Preclinical evaluation of a tailormade DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 56:914–920CrossRefPubMed

31.

Ahmadzadehfar H, Rahbar K, Kurpig S et al (2015) Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study. EJNMMI Res. doi:10.1186/s13550-015-0114-2

32.

Pfestroff A, Luster M, Jilg CA et al (2015) Current status and future perspectives of PSMA-targeted therapy in Europe: opportunity knocks. Eur J Nucl Med Mol Imaging 42:1971–1975CrossRefPubMed

33.

Parsons JT, Bova FJ, Mendenhall WM et al (1996) Response of the normal eye to high dose radiotherapy. Oncology 10:837–847PubMed

34.

Buchali A, Schröder C, Sidow D, Blank E (1991) Influence of the radiation dose to salivary glands on xerostomia in patients with head and neck carcinomas. J Cancer Ther 4:188–194CrossRef

35.

Emami B, Lyman J, Brown A et al (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109–122CrossRefPubMed

36.

Yin G, Xiong G, Zhao C, Chen Y (2010) Damage of nasal mucociliary movement after intensity-modulated radiation therapy of nasopharyngeal carcinoma. Chin J Cancer 29:824–829CrossRefPubMed

37.

Larson M, Bernhardt P, Svensson JB et al (2012) Estimation of absorbed dose to the kidneys in patients with ¹⁷⁷Lu-octreotate: comparison between methods based on planar scintigraphy. EJNMMI Res. doi:10.1186/2191-219X-2-49

38.

Siegel JA, Thomas SR, Stubbs JB et al (1999) MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med 40:37S–61SPubMed

Title: Lacrimal Glands May Represent Organs at Risk for Radionuclide Therapy of Prostate Cancer with [177Lu]DKFZ-PSMA-617
Authors: Melanie Hohberg
Wolfgang Eschner
Matthias Schmidt
Markus Dietlein
Carsten Kobe
Thomas Fischer
Alexander Drzezga
Markus Wild
Publication date: 01-06-2016
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 3/2016
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-016-0942-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Lacrimal Glands May Represent Organs at Risk for Radionuclide Therapy of Prostate Cancer with [¹⁷⁷Lu]DKFZ-PSMA-617

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2016

In Vitro and In Vivo Comparison of Selected Ga-68 and Zr-89 Labelled Siderophores

Imaging CXCR4 Expression with 99mTc-Radiolabeled Small-Interference RNA in Experimental Human Breast Cancer Xenografts

In Vivo Evaluation of a Bombesin Analogue Labeled with Ga-68 and Co-55/57

Image quality of Zr-89 PET imaging in the Siemens microPET Focus 220 preclinical scanner

Magnetic Targeting and Delivery of Drug-Loaded SWCNTs Theranostic Nanoprobes to Lung Metastasis in Breast Cancer Animal Model: Noninvasive Monitoring Using Magnetic Resonance Imaging

Gallium-68 Complexes Conjugated to Pittsburgh Compound B: Radiolabeling and Biological Evaluation