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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-03-2021 | Hepatocellular Carcinoma | Original Article

[⁶⁸ Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma

Authors: Jolanta Kunikowska, Bartosz Cieślak, Beata Gierej, Waldemar Patkowski, Leszek Kraj, Marcin Kotulski, Krzysztof Zieniewicz, Leszek Królicki

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2021

Abstract

Purpose

Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [⁶⁸Ga]Ga-PSMA-11 in HCC and its impact on patient management.

Methods

Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, single-institution study. All patients underwent contrast-enhanced MRI/CT, [⁶⁸Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions.

Results

No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [⁶⁸Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUV_max) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [⁶⁸Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC.

Conclusion

[⁶⁸Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.

Villanueva A. Hepatocellular carcinoma. New England Journal of Medicine. 2019;380(15):1450–62. https://doi.org/10.1056/NEJMra1713263.CrossRef

Tan CH, Low, S-CA, Thng CH. APASL and AASLD consensus guidelines on imaging diagnosis of hepatocellular carcinoma: a review. Int J Hepatol. 2011;2011:519783-. doi:https://doi.org/10.4061/2011/519783.

Bertagna F, Bertoli M, Bosio G, Biasiotto G, Sadeghi R, Giubbini R, et al. Diagnostic role of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: a systematic review and meta-analysis. Hepatology International. 2014;8(4):493–500. https://doi.org/10.1007/s12072-014-9566-0.CrossRefPubMed

Kunikowska J, Bartosz K, Leszek K. Glioblastoma multiforme: another potential application for 68Ga-PSMA PET/CT as a guide for targeted therapy. European Journal of Nuclear Medicine and Molecular Imaging. 2018;45(5):886–7. https://doi.org/10.1007/s00259-018-3934-2.CrossRefPubMed

Kunikowska J, Kulinski R, Muylle K, Koziara H, Królicki L. 68Ga–prostate-specific membrane antigen-11 PET/CT: a new imaging option for recurrent glioblastoma multiforme? Clinical Nuclear Medicine. 2020;45(1).

Salas Fragomeni RA, Amir T, Sheikhbahaei S, Harvey SC, Javadi MS, Solnes LB, et al. Imaging of nonprostate cancers using PSMA-targeted radiotracers: rationale, current state of the field, and a call to arms. J Nucl Med. 2018;59(6):871–7. https://doi.org/10.2967/jnumed.117.203570.CrossRefPubMed

Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clinical Cancer Research. 1997;3(1):81.PubMed

Milowsky MI, Nanus DM, Kostakoglu L, Sheehan CE, Vallabhajosula S, Goldsmith SJ, et al. Vascular targeted therapy with anti–prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. Journal of Clinical Oncology. 2007;25(5):540–7. https://doi.org/10.1200/JCO.2006.07.8097.CrossRefPubMed

Kratochwil C, Afshar-Oromieh A, Kopka K, Haberkorn U, Giesel FL. Current status of prostate-specific membrane antigen targeting in nuclear medicine: clinical translation of chelator containing prostate-specific membrane antigen ligands into diagnostics and therapy for prostate cancer. Seminars in Nuclear Medicine. 2016;46(5):405–18. https://doi.org/10.1053/j.semnuclmed.2016.04.004.CrossRefPubMed

10.

Werner RA, Derlin T, Lapa C, Sheikbahaei S, Higuchi T, Giesel FL, et al. (18)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging. Theranostics. 2020;10:1):1–16. https://doi.org/10.7150/thno.37894.CrossRefPubMedPubMedCentral

11.

Jiao D, Li Y, Yang F, Han D, Wu J, Shi S, et al. Expression of prostate-specific membrane antigen in tumor-associated vasculature predicts poor prognosis in hepatocellular carcinoma. Clin Transl Gastroenterol. 2019. https://doi.org/10.14309/ctg.0000000000000041.

12.

Kesler M, Levine C, Hershkovitz D, Mishani E, Menachem Y, Lerman H, et al. (68)Ga-PSMA is a novel PET-CT tracer for imaging of hepatocellular carcinoma: a prospective pilot study. J Nucl Med. 2018. https://doi.org/10.2967/jnumed.118.214833.

13.

Kuyumcu S, Has-Simsek D, Iliaz R, Sanli Y, Buyukkaya F, Akyuz F, et al. Evidence of prostate-specific membrane antigen expression in hepatocellular carcinoma using 68Ga-PSMA PET/CT. Clin Nucl Med. 2019;44(9):702–6. https://doi.org/10.1097/RLU.0000000000002701.CrossRefPubMed

14.

Das J, Ray S, Tapadia R, Midha D, Mallick I. Prostate-specific membrane antigen-expressing hepatic lesion: metastatic or hepatocellular carcinoma. Indian J Nucl Med. 2020;35(1):58–60. https://doi.org/10.4103/ijnm.IJNM_145_19.CrossRefPubMed

15.

Patel D, Loh H, Le K, Stevanovic A, Mansberg R. Incidental detection of hepatocellular carcinoma on 68Ga-labeled prostate-specific membrane antigen PET/CT. Clinical Nuclear Medicine. 2017;42(11).

16.

Taneja S, Taneja R, Kashyap V, Jha A, Jena A. 68Ga-PSMA uptake in hepatocellular carcinoma. Clinical Nuclear Medicine. 2017;42(1).

17.

Soydal C, Alkan A, Ozkan E, Demirkazık A, Kucuk N. Ga-68 PSMA accumulation in hepatocellular carcinoma. Journal of Gastroenterology, Pancreatology & Liver Disorders. 2017;4:1. https://doi.org/10.15226/2374-815X/4/2/00180.CrossRef

18.

Sasikumar A, Joy A, Nanabala R, Pillai MRA, Thomas B, Vikraman KR. 68Ga-PSMA PET/CT imaging in primary hepatocellular carcinoma. European Journal of Nuclear Medicine and Molecular Imaging. 2016;43(4):795–6. https://doi.org/10.1007/s00259-015-3297-x.CrossRefPubMed

19.

Tolkach Y, Goltz D, Kremer A, Ahmadzadehfar H, Bergheim D, Essler M, et al. Prostate-specific membrane antigen expression in hepatocellular carcinoma: potential use for prognosis and diagnostic imaging. Oncotarget. 2019;10(41):4149–60. https://doi.org/10.18632/oncotarget.27024.CrossRefPubMedPubMedCentral

20.

Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19(6):825–33. https://doi.org/10.1016/S1470-2045(18)30198-0.CrossRefPubMed

21.

Kratochwil C, Fendler W, Eiber M, Baum RP, Bozkurt M, Czernin J, et al. EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT). European Journal of Nuclear Medicine and Molecular Imaging. 2019;46. https://doi.org/10.1007/s00259-019-04485-3.

22.

Mittlmeier LM, Unterrainer M, Todica A, Cyran CC, Rodler S, Bartenstein P, et al. PSMA PET/CT for tyrosine-kinase inhibitor monitoring in metastatic renal cell carcinoma. European Journal of Nuclear Medicine and Molecular Imaging. 2020;47(9):2216–7. https://doi.org/10.1007/s00259-019-04636-6.CrossRefPubMed

23.

Kunikowska J, Charzyńska I, Kuliński R, Pawlak D, Maurin M, Królicki L. Tumor uptake in glioblastoma multiforme after IV injection of [177Lu]Lu-PSMA-617. European Journal of Nuclear Medicine and Molecular Imaging. 2020;47(6):1605–6. https://doi.org/10.1007/s00259-020-04715-z.CrossRefPubMedPubMedCentral

Title: [68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma
Authors: Jolanta Kunikowska
Bartosz Cieślak
Beata Gierej
Waldemar Patkowski
Leszek Kraj
Marcin Kotulski
Krzysztof Zieniewicz
Leszek Królicki
Publication date: 01-03-2021
Publisher: Springer Berlin Heidelberg
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Positron Emission Tomography
Computed Tomography
Computed Tomography
Magnetic Resonance Imaging
Magnetic Resonance Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-020-05017-0

At a glance: The STEP trials

Springer Medicine

[⁶⁸ Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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