Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 9/2016

01-08-2016 | Original Article

Radiation dosimetry of 68Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing

Authors: Ali Afshar-Oromieh, Henrik Hetzheim, Wolfgang Kübler, Clemens Kratochwil, Frederik L. Giesel, Thomas A. Hope, Matthias Eder, Michael Eisenhut, Klaus Kopka, Uwe Haberkorn

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2016

Login to get access

Abstract

Purpose

The clinical introduction of 68Ga-PSMA-11 (“HBED-CC”) ligand targeting the prostate-specific membrane antigen (PSMA) has been regarded as a significant step forward in the diagnosis of prostate cancer (PCa). In this study, we provide human dosimetry and data on optimal timing of PET imaging after injection.

Methods

Four patients with recurrent PCa were referred for 68Ga-PSMA-11 PET/CT. Whole-body PET/CTlow-dose scans were conducted at 5 min, and 1, 2, 3, 4 and 5 h after injection of 152–198 MBq 68Ga-PSMA-11. Organs of moderate to high uptake were used as source organs; their total activity was determined at all measured time points. Time–activity curves were created for each source organ as well as for the remainder. The radiation exposure of a 68Ga-PSMA-11 PET was identified using the OLINDA-EXM software. In addition, tracer uptake was measured in 16 sites of metastases.

Results

The highest tracer uptake was observed in the kidneys, liver, upper large intestine, and the urinary bladder. Mean organ doses were: kidneys 0.262 ± 0.098 mGy/MBq, liver 0.031 ± 0.004 mGy/MBq, upper large intestine 0.054 ± 0.041 mGy/MBq, urinary bladder 0.13 ± 0.059 mGy/MBq. The calculated mean effective dose was 0.023 ± 0.004 mSv/MBq (=0.085 ± 0.015 rem/mCi). Most tumor lesions (n = 16) were visible at 3 h p.i., while at all other time points many were not qualitatively present (10/16 visible at 1 h p.i.).

Conclusions

The mean effective dose of a 68Ga-PSMA-11 PET is 0.023 mSv/MBq. A 3-h delay after injection was optimal timing for 68Ga-PSMA-11 PET/CT in this patient cohort.
Appendix
Available only for authorised users
Literature
2.
go back to reference Schmid DT, John H, Zweifel R, Cservenyak T, Westera G, Goerres GW, et al. Fluorocholine PET/CT in patients with prostate cancer: initial experience. Radiology. 2005;235:623–8.CrossRefPubMed Schmid DT, John H, Zweifel R, Cservenyak T, Westera G, Goerres GW, et al. Fluorocholine PET/CT in patients with prostate cancer: initial experience. Radiology. 2005;235:623–8.CrossRefPubMed
3.
go back to reference Igerc I, Kohlfurst S, Gallowitsch HJ, Matschnig S, Kresnik E, Gomez-Segovia I, et al. The value of 18F-choline PET/CT in patients with elevated PSA-level and negative prostate needle biopsy for localisation of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:976–83.CrossRefPubMed Igerc I, Kohlfurst S, Gallowitsch HJ, Matschnig S, Kresnik E, Gomez-Segovia I, et al. The value of 18F-choline PET/CT in patients with elevated PSA-level and negative prostate needle biopsy for localisation of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:976–83.CrossRefPubMed
4.
go back to reference Kwee SA, DeGrado T. Prostate biopsy guided by 18F-fluorocholine PET in men with persistently elevated PSA levels. Eur J Nucl Med Mol Imaging. 2008;35:1567–9. author reply 1570.CrossRefPubMed Kwee SA, DeGrado T. Prostate biopsy guided by 18F-fluorocholine PET in men with persistently elevated PSA levels. Eur J Nucl Med Mol Imaging. 2008;35:1567–9. author reply 1570.CrossRefPubMed
5.
go back to reference Hacker A, Jeschke S, Leeb K, Prammer K, Ziegerhofer J, Sega W, et al. Detection of pelvic lymph node metastases in patients with clinically localized prostate cancer: comparison of [18F]fluorocholine positron emission tomography-computerized tomography and laparoscopic radioisotope guided sentinel lymph node dissection. J Urol. 2006;176:2014-8-9. Hacker A, Jeschke S, Leeb K, Prammer K, Ziegerhofer J, Sega W, et al. Detection of pelvic lymph node metastases in patients with clinically localized prostate cancer: comparison of [18F]fluorocholine positron emission tomography-computerized tomography and laparoscopic radioisotope guided sentinel lymph node dissection. J Urol. 2006;176:2014-8-9.
6.
go back to reference Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52:637–40.CrossRefPubMed Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52:637–40.CrossRefPubMed
7.
go back to reference Mannweiler S, Amersdorfer P, Trajanoski S, Terrett JA, King D, Mehes G. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res. 2009;15:167–72.CrossRefPubMed Mannweiler S, Amersdorfer P, Trajanoski S, Terrett JA, King D, Mehes G. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res. 2009;15:167–72.CrossRefPubMed
8.
go back to reference Hillier SM, Maresca KP, Femia FJ, Marquis JC, Foss CA, Nguyen N, et al. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res. 2009;69:6932–40.CrossRefPubMedPubMedCentral Hillier SM, Maresca KP, Femia FJ, Marquis JC, Foss CA, Nguyen N, et al. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res. 2009;69:6932–40.CrossRefPubMedPubMedCentral
9.
go back to reference Maresca KP, Hillier SM, Femia FJ, Keith D, Barone C, Joyal JL, et al. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J Med Chem. 2009;52:347–57.CrossRefPubMed Maresca KP, Hillier SM, Femia FJ, Keith D, Barone C, Joyal JL, et al. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J Med Chem. 2009;52:347–57.CrossRefPubMed
10.
go back to reference Cho SY, Gage KL, Mease RC, Senthamizhchelvan S, Holt DP, Jeffrey-Kwanisai A, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med Off Publ Soc Nucl Med. 2012;53:1883–91. Cho SY, Gage KL, Mease RC, Senthamizhchelvan S, Holt DP, Jeffrey-Kwanisai A, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med Off Publ Soc Nucl Med. 2012;53:1883–91.
11.
go back to reference Barrett JA, Coleman RE, Goldsmith SJ, Vallabhajosula S, Petry NA, Cho S, et al. First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer. J Nucl Med Off Publ Soc Nucl Med. 2013;54:380–7. Barrett JA, Coleman RE, Goldsmith SJ, Vallabhajosula S, Petry NA, Cho S, et al. First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer. J Nucl Med Off Publ Soc Nucl Med. 2013;54:380–7.
12.
go back to reference 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 Off J Am Assoc Cancer Res. 2013;19:5182–91.CrossRef 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 Off J Am Assoc Cancer Res. 2013;19:5182–91.CrossRef
13.
go back to reference Hillier SM, Maresca KP, Lu G, Merkin RD, Marquis JC, Zimmerman CN, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med Off Publ Soc Nucl Med. 2013;54:1369–76. Hillier SM, Maresca KP, Lu G, Merkin RD, Marquis JC, Zimmerman CN, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med Off Publ Soc Nucl Med. 2013;54:1369–76.
14.
go back to reference Banerjee SR, Pullambhatla M, Foss CA, Nimmagadda S, Ferdani R, Anderson CJ, et al. 64Cu-labeled inhibitors of prostate-specific membrane antigen for PET imaging of prostate cancer. J Med Chem. 2014;57:2657–69.CrossRefPubMedPubMedCentral Banerjee SR, Pullambhatla M, Foss CA, Nimmagadda S, Ferdani R, Anderson CJ, et al. 64Cu-labeled inhibitors of prostate-specific membrane antigen for PET imaging of prostate cancer. J Med Chem. 2014;57:2657–69.CrossRefPubMedPubMedCentral
15.
go back to reference Szabo Z, Mena E, Rowe SP, Plyku D, Nidal R, Eisenberger MA, et al. Initial evaluation of [(18)F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol MIB Off Publ Acad Mol Imaging. 2015;17:565–74.CrossRef Szabo Z, Mena E, Rowe SP, Plyku D, Nidal R, Eisenberger MA, et al. Initial evaluation of [(18)F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol MIB Off Publ Acad Mol Imaging. 2015;17:565–74.CrossRef
16.
go back to reference Schäfer M, Bauder-Wüst U, Leotta K, Zoller F, Mier W, Haberkorn U, et al. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res. 2012;2:23.CrossRefPubMedPubMedCentral Schäfer M, Bauder-Wüst U, Leotta K, Zoller F, Mier W, Haberkorn U, et al. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res. 2012;2:23.CrossRefPubMedPubMedCentral
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference Afshar-Oromieh A, Haberkorn U, Eder M, Eisenhut M, Zechmann CM. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH. Eur J Nucl Med Mol Imaging. 2012;39:1085–6.CrossRefPubMed Afshar-Oromieh A, Haberkorn U, Eder M, Eisenhut M, Zechmann CM. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH. Eur J Nucl Med Mol Imaging. 2012;39:1085–6.CrossRefPubMed
19.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
go back to reference Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:11–20.CrossRefPubMed Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:11–20.CrossRefPubMed
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
go back to reference Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med Off Publ Soc Nucl Med. 2015;56:668–74. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med Off Publ Soc Nucl Med. 2015;56:668–74.
23.
go back to reference Eder M, Neels O, Müller M, Bauder-Wüst U, Remde Y, Schäfer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharm Basel Switz. 2014;7:779–96. Eder M, Neels O, Müller M, Bauder-Wüst U, Remde Y, Schäfer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharm Basel Switz. 2014;7:779–96.
24.
go back to reference Reza Ay M, Zaidi H. Computed tomography-based attenuation correction in neurological positron emission tomography: evaluation of the effect of the X-ray tube voltage on quantitative analysis. Nucl Med Commun. 2006;27:339–46.CrossRefPubMed Reza Ay M, Zaidi H. Computed tomography-based attenuation correction in neurological positron emission tomography: evaluation of the effect of the X-ray tube voltage on quantitative analysis. Nucl Med Commun. 2006;27:339–46.CrossRefPubMed
25.
go back to reference Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46:1023–7.PubMed Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46:1023–7.PubMed
26.
go back to reference 1990 Recommendations of the International Commission on Radiological Protection. Ann ICRP. 1991;21:1–201. 1990 Recommendations of the International Commission on Radiological Protection. Ann ICRP. 1991;21:1–201.
28.
go back to reference Herrmann K, Bluemel C, Weineisen M, Schottelius M, Wester H-J, Czernin J, et al. Biodistribution and radiation dosimetry for a probe targeting prostate-specific membrane antigen for imaging and therapy. J Nucl Med Off Publ Soc Nucl Med. 2015;56:855–61. Herrmann K, Bluemel C, Weineisen M, Schottelius M, Wester H-J, Czernin J, et al. Biodistribution and radiation dosimetry for a probe targeting prostate-specific membrane antigen for imaging and therapy. J Nucl Med Off Publ Soc Nucl Med. 2015;56:855–61.
29.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
30.
go back to reference Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, et al. The Theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med Off Publ Soc Nucl Med. 2015;56:1697–705. Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, et al. The Theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med Off Publ Soc Nucl Med. 2015;56:1697–705.
Metadata
Title
Radiation dosimetry of 68Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing
Authors
Ali Afshar-Oromieh
Henrik Hetzheim
Wolfgang Kübler
Clemens Kratochwil
Frederik L. Giesel
Thomas A. Hope
Matthias Eder
Michael Eisenhut
Klaus Kopka
Uwe Haberkorn
Publication date
01-08-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-016-3419-0

Other articles of this Issue 9/2016

European Journal of Nuclear Medicine and Molecular Imaging 9/2016 Go to the issue