Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 7/2018

01-07-2018 | Original Article

Tracer uptake in mediastinal and paraaortal thoracic lymph nodes as a potential pitfall in image interpretation of PSMA ligand PET/CT

Authors: Ali Afshar-Oromieh, Lars Peter Sattler, Katja Steiger, Tim Holland-Letz, Marcelo Livorsi da Cunha, Walter Mier, Oliver Neels, Klaus Kopka, Wilko Weichert, Uwe Haberkorn

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2018

Login to get access

Abstract

Purpose

Since the introduction of 68Ga-PSMA-11 PET/CT for imaging prostate cancer (PC) we have frequently observed mediastinal lymph nodes (LN) showing tracer uptake despite being classified as benign. The aim of this evaluation was to further analyze such LN.

Methods

Two patient groups with biphasic 68Ga-PSMA-11 PET/CT at 1 h and 3 h p.i. were included in this retrospective evaluation. Group A (n = 38) included patients without LN metastases, and group B (n = 43) patients with LN metastases of PC. SUV of mediastinal/paraaortal LN of group A (n = 100) were compared to SUV of LN metastases of group B (n = 91). Additionally, 22 randomly selected mediastinal and paraaortal LN of patients without PC were immunohistochemically (IHC) analyzed for PSMA expression.

Results

In group A, 7/38 patients (18.4%) presented with at least one PSMA-positive mediastinal LN at 1 h p.i. and 3/38 (7.9%) positive LN at 3 h p.i. with a SUVmax of 2.3 ± 0.7 at 1 h p.i. (2.0 ± 0.7 at 3 h p.i.). A total of 11 PSMA-positive mediastinal/paraaortal LN were detected in nine patients considering both imaging timing points. SUVmax of LN-metastases was 12.5 ± 13.2 at 1 h p.i. (15.8 ± 17.0 at 3 h p.i.). SUVmax increased clearly (> 10%) between 1 h and 3 h p.i. in 76.9% of the LN metastases, and decreased significantly in 72.7% of the mediastinal/paraaortal LN. By IHC, PSMA-expression was observed in intranodal vascular endothelia of all investigated LN groups and to differing degrees within germinal centers of 15/22 of them (68.1%). Expression was stronger in mediastinal nodes (p = 0.038) and when follicular hyperplasia was present (p = 0.050).

Conclusion

PSMA-positive mediastinal/paraaortal benign LN were visible in a notable proportion of patients. PSMA-positivity on the histopathological level was associated with the activation state of the LN. However, in contrast to LN metastases of PC, they presented with significantly lower uptake, which, in addition, usually decreased over time.
Literature
2.
go back to reference Israeli RS, Powell CT, Corr JG, Fair WR, Heston WD. Expression of the prostate-specific membrane antigen. Cancer Res. 1994;54:1807–11.PubMed Israeli RS, Powell CT, Corr JG, Fair WR, Heston WD. Expression of the prostate-specific membrane antigen. Cancer Res. 1994;54:1807–11.PubMed
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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. 2015;56:668–74.CrossRefPubMed 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. 2015;56:668–74.CrossRefPubMed
9.
go back to reference Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of (68)Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017:44(8):1258–68.CrossRefPubMedPubMedCentral Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of (68)Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017:44(8):1258–68.CrossRefPubMedPubMedCentral
10.
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
11.
go back to reference Afshar-Oromieh A, Haberkorn U, Zechmann C, Armor T, Mier W, Spohn F, et al. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with (131)I-MIP-1095. Eur J Nucl Med Mol Imaging. 2017;44:950–9.CrossRefPubMedPubMedCentral Afshar-Oromieh A, Haberkorn U, Zechmann C, Armor T, Mier W, Spohn F, et al. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with (131)I-MIP-1095. Eur J Nucl Med Mol Imaging. 2017;44:950–9.CrossRefPubMedPubMedCentral
13.
go back to reference Sheikhbahaei S, Afshar-Oromieh A, Eiber M, Solnes LB, Javadi MS, Ross AE, et al. Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging. Eur J Nucl Med Mol Imaging. 2017;44(12):2117–36CrossRefPubMed Sheikhbahaei S, Afshar-Oromieh A, Eiber M, Solnes LB, Javadi MS, Ross AE, et al. Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging. Eur J Nucl Med Mol Imaging. 2017;44(12):2117–36CrossRefPubMed
14.
go back to reference Krohn T, Verburg FA, Pufe T, Neuhuber W, Vogg A, Heinzel A, et al. 68Ga-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.CrossRefPubMed Krohn T, Verburg FA, Pufe T, Neuhuber W, Vogg A, Heinzel A, et al. 68Ga-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.CrossRefPubMed
15.
go back to reference Afshar-Oromieh A, Hetzheim H, Kübler W, Kratochwil C, Giesel FL, Hope TA, et al. Radiation dosimetry of (68)Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing. Eur J Nucl Med Mol Imaging. 2016;43:1611–20.CrossRefPubMed Afshar-Oromieh A, Hetzheim H, Kübler W, Kratochwil C, Giesel FL, Hope TA, et al. Radiation dosimetry of (68)Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing. Eur J Nucl Med Mol Imaging. 2016;43:1611–20.CrossRefPubMed
16.
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.
17.
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. 2015;56:855–61.CrossRefPubMedPubMedCentral 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. 2015;56:855–61.CrossRefPubMedPubMedCentral
18.
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. 2015;56:1697–705.CrossRefPubMed 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. 2015;56:1697–705.CrossRefPubMed
19.
go back to reference Afshar-Oromieh A, Sattler LP, Mier W, Hadaschik B, Debus J, Holland-Letz T, et al. The clinical impact of additional late PET/CT imaging with 68Ga-PSMA-11 (HBED-CC) in the diagnosis of prostate cancer. J Nucl Med. 2017;58(5):750–755CrossRefPubMed Afshar-Oromieh A, Sattler LP, Mier W, Hadaschik B, Debus J, Holland-Letz T, et al. The clinical impact of additional late PET/CT imaging with 68Ga-PSMA-11 (HBED-CC) in the diagnosis of prostate cancer. J Nucl Med. 2017;58(5):750–755CrossRefPubMed
20.
go back to reference Sahlmann C-O, Meller B, Bouter C, Ritter CO, Ströbel P, Lotz J, et al. Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma. Eur J Nucl Med Mol Imaging. 2016;43:898–905.CrossRefPubMed Sahlmann C-O, Meller B, Bouter C, Ritter CO, Ströbel P, Lotz J, et al. Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma. Eur J Nucl Med Mol Imaging. 2016;43:898–905.CrossRefPubMed
21.
go back to reference Wondergem M, van der Zant F, Knol R, Lazarenko S, Pruim J, de Jong IJ. 18F-DCFPyL PET/CT in the detection of prostate cancer at 60 and 120 minutes; detection rate, image quality, activity kinetics and biodistribution. J Nucl Med. 2017;58(11):1797–1804CrossRefPubMed Wondergem M, van der Zant F, Knol R, Lazarenko S, Pruim J, de Jong IJ. 18F-DCFPyL PET/CT in the detection of prostate cancer at 60 and 120 minutes; detection rate, image quality, activity kinetics and biodistribution. J Nucl Med. 2017;58(11):1797–1804CrossRefPubMed
Metadata
Title
Tracer uptake in mediastinal and paraaortal thoracic lymph nodes as a potential pitfall in image interpretation of PSMA ligand PET/CT
Authors
Ali Afshar-Oromieh
Lars Peter Sattler
Katja Steiger
Tim Holland-Letz
Marcelo Livorsi da Cunha
Walter Mier
Oliver Neels
Klaus Kopka
Wilko Weichert
Uwe Haberkorn
Publication date
01-07-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-3965-8

Other articles of this Issue 7/2018

European Journal of Nuclear Medicine and Molecular Imaging 7/2018 Go to the issue