Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using 11C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand 68Ga-PSMA-11 with 11C-choline in patients with primary and recurrent prostate cancer.
123 patients underwent a whole-body PET/CT examination using 68Ga-PSMA-11 and 11C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging.
In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using 68Ga-PSMA-11 showed a significantly higher uptake and detection rate than 11C-choline PET. Also 68Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients’ biochemical relapse. Significantly more bone lesions were detected by 68Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per 11C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by 68Ga-PSMA-11 PET.
Thus, PET using 68Ga-PSMA-11 showed a higher detection rate than 11C-choline PET for lymph nodes as well as bone lesions. However, we found lymph nodes and bone lesions which were not concordant applying both tracers.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
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. doi:10.1007/s00259-012-2298-2.
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. doi:10.1007/s00259-014-2713-y.
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. doi:10.1007/s00259-013-2525-5.
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. doi:10.1007/s00259-014-2949-6.
Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of Hybrid (6)(8)Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy. J Nucl Med. 2015;56:668–74. doi:10.2967/jnumed.115.154153.
Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma - A study of 184 cases. Cancer. 1998;82:2256–61.
Yao V, Berkman CE, Choi JK, O’Keefe DS, Bacich DJ. Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the Non-Polyglutamated folate. Folic Acid Prostate. 2010;70:305–16. doi:10.1002/Pros.21065.
Yao V, Bacich DJ. Prostate specific membrane antigen (PSMA) expression gives prostate cancer cells a growth advantage in a physiologically relevant folate environment in vitro. Prostate. 2006;66:867–75. doi:10.1002/Pros.20361.
Minner S, Wittmer C, Graefen M, Salomon G, Steuber T, Haese A, et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate. 2011;71:281–8. doi:10.1002/pros.21241.
Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients Who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56:1185–90. doi:10.2967/jnumed.115.160382.
Ost P, Jereczek-Fossa BA, As NV, Zilli T, Muacevic A, Olivier K, et al. Progression-free survival following stereotactic body radiotherapy for oligometastatic prostate cancer treatment-naive recurrence: a multi-institutional analysis. Eur Urol. 2015. doi:10.1016/j.eururo.2015.07.004.
Reischl G, Bieg C, Schmiedl O, Solbach C, Machulla HJ. Highly efficient automated synthesis of [(11)C]choline for multi dose utilization. Appl Radiat Isot. 2004;60:835–8. doi:10.1016/j.apradiso.2004.01.006.
Eder M, Schafer M, Bauder-Wust U, Hull WE, Wangler 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. doi:10.1021/bc200279b.
Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med. 2007;48:1741–8. doi:10.2967/jnumed.107.040378.
Jakoby BW, Bercier Y, Conti M, Casey ME, Bendriem B, Townsend DW. Physical and clinical performance of the mCT time-of-flight PET/CT scanner. Phys Med Biol. 2011;56:2375–89. doi:10.1088/0031-9155/56/8/004.
Brendle C, Kupferschlager J, Nikolaou K, la Fougere C, Gatidis S, Pfannenberg C. Is the standard uptake value (SUV) appropriate for quantification in clinical PET imaging? - Variability induced by different SUV measurements and varying reconstruction methods. Eur J Radiol. 2015;84:158–62. doi:10.1016/j.ejrad.2014.10.018.
Prieto E, Dominguez-Prado I, Garcia-Velloso MJ, Penuelas I, Richter JA, Marti-Climent JM. Impact of time-of-flight and point-spread-function in SUV quantification for oncological PET. Clin Nucl Med. 2013;38:103–9. doi:10.1097/RLU.0b013e318279b9df.
Krohn T, Verburg FA, Pufe T, Neuhuber W, Vogg A, Heinzel A, et al. [(68)Ga]PSMA-HBED uptake mimicking lymph node metastasis in coeliac ganglia: an important pitfall in clinical practice. Eur J Nucl Med Mol Imaging. 2015;42:210–4. doi:10.1007/s00259-014-2915-3.
Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13:8–10.
Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol. 2011;8:378–82. doi:10.1038/nrclinonc.2011.44.
Schwarzenbock S, Souvatzoglou M, Krause BJ. Choline PET and PET/CT in primary diagnosis and staging of prostate cancer. Theranostics. 2012;2:318–30. doi:10.7150/thno.4008.
Evangelista L, Guttilla A, Zattoni F, Muzzio PC. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Eur Urol. 2013;63:1040–8. doi:10.1016/j.eururo.2012.09.039.
Umbehr MH, Muntener M, Hany T, Sulser T, Bachmann LM. The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur Urol. 2013;64:106–17. doi:10.1016/j.eururo.2013.04.019.
Cimitan M, Bortolus R, Morassut S, Canzonieri V, Garbeglio A, Baresic T, et al. [18F]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients. Eur J Nucl Med Mol Imaging. 2006;33:1387–98. doi:10.1007/s00259-006-0150-2.
Reske SN, Blumstein NM, Glatting G. [11C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2008;35:9–17. doi:10.1007/s00259-007-0530-2.
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. doi:10.1097/MNM.0000000000000290.
Krause BJ, Souvatzoglou M, Tuncel M, Herrmann K, Buck AK, Praus C, et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:18–23. doi:10.1007/s00259-007-0581-4.
Castellucci P, Fuccio C, Rubello D, Schiavina R, Santi I, Nanni C, et al. Is there a role for C-11-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase < 1.5 ng/ml? Eur J Nucl Med Mol Imaging. 2011;38:55–63. doi:10.1007/s00259-010-1604-0.
Hijazi S, Meller B, Leitsmann C, Strauss A, Meller J, Ritter CO, et al. Pelvic lymph node dissection for nodal oligometastatic prostate cancer detected by (68) Ga-PSMA-positron emission tomography/computerized tomography. Prostate. 2015;75:1934–40. doi:10.1002/pros.23091.
Herlemann A, Wenter V, Kretschmer A, Thierfelder K, Bartenstein P, Faber C, et al. 68Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol. 2016.
Takeda A, Sanuki N, Kunieda E. Role of stereotactic body radiotherapy for oligometastasis from colorectal cancer. World J Gastroenterol. 2014;20:4220–9. doi:10.3748/wjg.v20.i15.4220.
Shimada Y, Saji H, Kakihana M, Kajiwara N, Ohira T, Ikeda N. Survival outcomes for oligometastasis in resected non-small cell lung cancer. Asian Cardiovasc Thorac Ann. 2015;23:937–44. doi:10.1177/0218492315596463.
Farsad M, Schiavina R, Castellucci P, Nanni C, Corti B, Martorana G, et al. Detection and localization of prostate cancer: correlation of (11)C-choline PET/CT with histopathologic step-section analysis. J Nucl Med. 2005;46:1642–9.
Hartenbach M, Hartenbach S, Bechtloff W, Danz B, Kraft K, Klemenz B, et al. Combined PET/MRI improves diagnostic accuracy in patients with prostate cancer: a prospective diagnostic trial. Clin Cancer Res. 2014;20:3244–53. doi:10.1158/1078-0432.CCR-13-2653.
Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol. 2016. doi:10.1016/j.eururo.2015.12.053.
Abdollah F, Gandaglia G, Suardi N, Capitanio U, Salonia A, Nini A, et al. More extensive pelvic lymph node dissection improves survival in patients with node-positive prostate cancer. Eur Urol. 2015;67:212–9. doi:10.1016/j.eururo.2014.05.011.
Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, et al. 68Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol. 2016. doi:10.1016/j.eururo.2015.12.051.
Schwenck J, Tabatabai G, Skardelly M, Reischl G, Beschorner R, Pichler B, et al. In vivo visualization of prostate-specific membrane antigen in glioblastoma. Eur J Nucl Med Mol Imaging. 2015;42:170–1. doi:10.1007/s00259-014-2921-5.
Demirci E, Ocak M, Kabasakal L, Decristoforo C, Talat Z, Halac M, et al. (68)Ga-PSMA PET/CT imaging of metastatic clear cell renal cell carcinoma. Eur J Nucl Med Mol Imaging. 2014;41:1461–2. doi:10.1007/s00259-014-2766-y.
van Waarde A, Jager PL, Ishiwata K, Dierckx RA, Elsinga PH. Comparison of sigma-ligands and metabolic PET tracers for differentiating tumor from inflammation. J Nucl Med. 2006;47:150–4.
Kobe C, Maintz D, Fischer T, Drzezga A, Chang DH. Prostate-specific membrane antigen PET/CT in splenic sarcoidosis. Clin Nucl Med. 2015;40:897–8. doi:10.1097/RLU.0000000000000827.
Hara T, Bansal A, DeGrado TR. Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells. Nucl Med Biol. 2006;33:977–84. doi:10.1016/j.nucmedbio.2006.08.002.
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. doi:10.1007/s12253-008-9104-2.
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.
All patients gave written informed consent for the purpose of anonymized evaluation and publication of their data. All reported investigations were conducted in accordance with the Helsinki Declaration and with national regulations. The data analysis was approved by the ethics committee of the University of Tübingen (416/2015R).
Nothing to declare.
Conception and design: JS, ClF, HR; Analysis and interpretation of data: JS, HR CP, ClF; Drafting manuscript and critical revision JS, ClF, HR, CP, SK, AS, GR and KN. All authors read and approved the final manuscript.
Electronic supplementary material
Below is the link to the electronic supplementary material.
(DOC 3350 kb)
Rights and permissions
About this article
Cite this article
Schwenck, J., Rempp, H., Reischl, G. et al. Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging 44, 92–101 (2017). https://doi.org/10.1007/s00259-016-3490-6
- Prostate cancer