nach oben

Erschienen in:

01.06.2023 | Special Section: PET/MR

Distribution of prostate specific membrane antigen (PSMA) on PET-MRI in patients with and without ovarian cancer

verfasst von: Elizabeth A. Sadowski, Brittany Lees, Alan B. McMillian, Joanna E. Kusmirek, Steve Y. Cho, Lisa M. Barroilhet

Erschienen in: Abdominal Radiology | Ausgabe 12/2023

Einloggen, um Zugang zu erhalten

Abstract

Objectives

Ovarian cancer is the most lethal cancer and future research needs to focus on the early detection and exploration of new therapeutic agents. The objectives of this proof-of-concept study are to assess the feasibility of PSMA 18F-DCFPyl PET/MR imaging for detecting ovarian cancer and to evaluate the PSMA distribution in patients with and without ovarian cancer.

Methods

This prospective pilot proof-of-concept study in patients with and without ovarian cancers occurred between October 2017 and January 2020. Patients were recruited from gynecologic oncology or hereditary ovarian cancer clinics, and underwent surgical removal of the uterus and ovaries for gynecologic indications. PSMA 18F-DCFPyl PET/MRI was obtained prior to standard of care surgery.

Results

Fourteen patients were scanned: four patients with normal ovaries, six patients with benign ovarian lesions, and four patients with malignant ovarian lesions. Tracer uptake in normal ovaries (SUVmax = 2.8 ± 0.4) was greater than blood pool (SUVmax = 1.8 ± 0.5, p < 0.0001). Tracer uptake in benign ovarian lesions (2.2 ± 1.0) did not differ significantly from blood pool (p = 0.331). Tracer uptake in ovarian cancer (SUVmax = 7.8 ± 3.8) was greater than blood pool (p < 0.0001), normal ovaries (p = 0.0014), and benign ovarian lesions (p = 0.005).

Conclusion

PET/MR imaging detected PSMA uptake in ovarian cancer, with little to no uptake in benign ovarian findings. These results are encouraging and further studies in a larger patient cohort would be useful to help determine the extent and heterogeneity of PSMA uptake in ovarian cancer patients.

Nur mit Berechtigung zugänglich

https://seer.cancer.gov/statfacts/html/ovary.html. SEER Stat Fact Sheets: Ovarian Cancer. Accessed November 18, 2020.

http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-survival-rates. American Cancer Society. http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-survival-rates. Published Accessed November 18, 2020.

Verheijen RH, Zweemer RP. Screening to improve ovarian cancer prognosis? Lancet (London, England) 2016;387(10022):921-923. https://doi.org/10.1016/s0140-6736(15)01236-2CrossRefPubMed

Vergote I, De Brabanter J, Fyles A, Bertelsen K, Einhorn N, Sevelda P, Gore ME, Kaern J, Verrelst H, Sjovall K, Timmerman D, Vandewalle J, Van Gramberen M, Trope CG. Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma. Lancet (London, England) 2001;357(9251):176-182. doi: https://doi.org/10.1016/s0140-6736(00)03590-xCrossRefPubMed

Khan SR, Arshad M, Wallitt K, Stewart V, Bharwani N, Barwick TD. What's New in Imaging for Gynecologic Cancer? Current oncology reports 2017;19(12):85. https://doi.org/10.1007/s11912-017-0640-3CrossRefPubMed

Nougaret S, Tardieu M, Vargas HA, Reinhold C, Vande Perre S, Bonanno N, Sala E, Thomassin-Naggara I. Ovarian cancer: An update on imaging in the era of radiomics. Diagnostic and interventional imaging 2019;100(10):647-655. https://doi.org/10.1016/j.diii.2018.11.007CrossRefPubMed

Langbein T, Weber WA, Eiber M. Future of Theranostics: An Outlook on Precision Oncology in Nuclear Medicine. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2019;60(Suppl 2):13s-19s. https://doi.org/10.2967/jnumed.118.220566CrossRefPubMed

Yordanova A, Eppard E, Kürpig S, Bundschuh RA, Schönberger S, Gonzalez-Carmona M, Feldmann G, Ahmadzadehfar H, Essler M. Theranostics in nuclear medicine practice. OncoTargets and therapy 2017;10:4821-4828. https://doi.org/10.2147/ott.s140671CrossRefPubMedPubMedCentral

Pillai MRA, Nanabala R, Joy A, Sasikumar A, Russ Knapp FF. Radiolabeled enzyme inhibitors and binding agents targeting PSMA: Effective theranostic tools for imaging and therapy of prostate cancer. Nuclear medicine and biology 2016;43(11):692-720. https://doi.org/10.1016/j.nucmedbio.2016.08.006CrossRefPubMed

10.

Herrmann K, Schwaiger M, Lewis JS, Solomon SB, McNeil BJ, Baumann M, Gambhir SS, Hricak H, Weissleder R. Radiotheranostics: a roadmap for future development. The Lancet Oncology 2020;21(3):e146-e156. https://doi.org/10.1016/s1470-2045(19)30821-6CrossRefPubMedPubMedCentral

11.

Fendler WP, Rahbar K, Herrmann K, Kratochwil C, Eiber M. (177)Lu-PSMA Radioligand Therapy for Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2017;58(8):1196-1200. https://doi.org/10.2967/jnumed.117.191023CrossRefPubMed

12.

von Eyben FE, Roviello G, Kiljunen T, Uprimny C, Virgolini I, Kairemo K, Joensuu T. Third-line treatment and (177)Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review. European journal of nuclear medicine and molecular imaging 2018;45(3):496-508. https://doi.org/10.1007/s00259-017-3895-xCrossRef

13.

Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best practice & research Clinical obstetrics & gynaecology 2017;41:3-14. https://doi.org/10.1016/j.bpobgyn.2016.08.006CrossRef

14.

Lee JM, Minasian L, Kohn EC. New strategies in ovarian cancer treatment. Cancer 2019;125 Suppl 24(Suppl 24):4623–4629. https://doi.org/10.1002/cncr.32544

15.

Kinoshita Y, Kuratsukuri K, Landas S, Imaida K, Rovito PM, Jr., Wang CY, Haas GP. Expression of prostate-specific membrane antigen in normal and malignant human tissues. World journal of surgery 2006;30(4):628-636. https://doi.org/10.1007/s00268-005-0544-5CrossRefPubMed

16.

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 : an official journal of the American Association for Cancer Research 1997;3(1):81-85.PubMed

17.

Van de Wiele C, Sathekge M, de Spiegeleer B, de Jonghe PJ, Beels L, Maes A. PSMA-Targeting Positron Emission Agents for Imaging Solid Tumors Other Than Non-Prostate Carcinoma: A Systematic Review. International journal of molecular sciences 2019;20(19). https://doi.org/10.3390/ijms20194886

18.

Salas Fragomeni RA, Amir T, Sheikhbahaei S, Harvey SC, Javadi MS, Solnes LB, Kiess AP, Allaf ME, Pomper MG, Gorin MA, Rowe SP. Imaging of Nonprostate Cancers Using PSMA-Targeted Radiotracers: Rationale, Current State of the Field, and a Call to Arms. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2018;59(6):871-877. https://doi.org/10.2967/jnumed.117.203570CrossRefPubMed

19.

Wernicke AG, Varma S, Greenwood EA, Christos PJ, Chao KS, Liu H, Bander NH, Shin SJ. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 2014;122(6):482-489. https://doi.org/10.1111/apm.12195CrossRefPubMed

20.

Schmidt LH, Heitkötter B, Schulze AB, Schliemann C, Steinestel K, Trautmann M, Marra A, Hillejan L, Mohr M, Evers G, Wardelmann E, Rahbar K, Görlich D, Lenz G, Berdel WE, Hartmann W, Wiewrodt R, Huss S. Prostate specific membrane antigen (PSMA) expression in non-small cell lung cancer. PloS one 2017;12(10):e0186280. https://doi.org/10.1371/journal.pone.0186280

21.

Shetty D, Loh H, Bui C, Mansberg R, Stevanovic A. Elevated 68Ga Prostate-Specific Membrane Antigen Activity in Metastatic Non-Small Cell Lung Cancer. Clinical nuclear medicine 2016;41(5):414-416. https://doi.org/10.1097/rlu.0000000000001139CrossRefPubMed

22.

Haffner MC, Kronberger IE, Ross JS, Sheehan CE, Zitt M, Mühlmann G, Ofner D, Zelger B, Ensinger C, Yang XJ, Geley S, Margreiter R, Bander NH. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Human pathology 2009;40(12):1754-1761. https://doi.org/10.1016/j.humpath.2009.06.003CrossRefPubMed

23.

Samplaski MK, Heston W, Elson P, Magi-Galluzzi C, Hansel DE. Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2011;24(11):1521-1529. https://doi.org/10.1038/modpathol.2011.112

24.

Kuyumcu S, Has-Simsek D, Iliaz R, Sanli Y, Buyukkaya F, Akyuz F, Turkmen C. Evidence of Prostate-Specific Membrane Antigen Expression in Hepatocellular Carcinoma Using 68Ga-PSMA PET/CT. Clinical nuclear medicine 2019;44(9):702-706. https://doi.org/10.1097/rlu.0000000000002701CrossRefPubMed

25.

Sawicki LM, Buchbender C, Boos J, Giessing M, Ermert J, Antke C, Antoch G, Hautzel H. Diagnostic potential of PET/CT using a (68)Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience. European journal of nuclear medicine and molecular imaging 2017;44(1):102-107. https://doi.org/10.1007/s00259-016-3360-2CrossRefPubMed

26.

Ahn T, Roberts MJ, Abduljabar A, Joshi A, Perera M, Rhee H, Wood S, Vela I. A Review of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in Renal Cell Carcinoma (RCC). Mol Imaging Biol 2019;21(5):799-807. https://doi.org/10.1007/s11307-018-01307-0CrossRefPubMed

27.

Rowe SP, Gorin MA, Hammers HJ, Som Javadi M, Hawasli H, Szabo Z, Cho SY, Pomper MG, Allaf ME. Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted ¹⁸F-DCFPyL PET/CT. Annals of nuclear medicine 2015;29(10):877-882. https://doi.org/10.1007/s12149-015-1017-zCrossRefPubMedPubMedCentral

28.

Wernicke AG, Kim S, Liu H, Bander NH, Pirog EC. Prostate-specific Membrane Antigen (PSMA) Expression in the Neovasculature of Gynecologic Malignancies: Implications for PSMA-targeted Therapy. Applied immunohistochemistry & molecular morphology : AIMM 2016. https://doi.org/10.1097/pai.0000000000000297CrossRef

29.

Hofstetter G, Grech C, Pils D, Pammer J, Neudert B, Pötsch N, Baltzer P, Traub-Weidinger T, Seebacher V, Aust S. Prostate-Specific Membrane Antigen (PSMA) Expression in Tumor-Associated Neovasculature Is an Independent Prognostic Marker in Patients with Ovarian Cancer. J Pers Med 2022;12(4). https://doi.org/10.3390/jpm12040551

30.

Wernicke AG, Kim S, Liu H, Bander NH, Pirog EC. Prostate-specific Membrane Antigen (PSMA) Expression in the Neovasculature of Gynecologic Malignancies: Implications for PSMA-targeted Therapy. Applied immunohistochemistry & molecular morphology : AIMM 2017;25(4):271-276. https://doi.org/10.1097/pai.0000000000000297CrossRef

31.

Metser U, Kulanthaivelu R, Chawla T, Johnson S, Avery L, Hussey D, Veit-Haibach P, Bernardini M, Hogen L. (18)F-DCFPyL PET/CT in advanced high-grade epithelial ovarian cancer: A prospective pilot study. Frontiers in oncology 2022;12:1025475. https://doi.org/10.3389/fonc.2022.1025475CrossRefPubMedPubMedCentral

32.

Vargas HA, Veeraraghavan H, Micco M, Nougaret S, Lakhman Y, Meier AA, Sosa R, Soslow RA, Levine DA, Weigelt B, Aghajanian C, Hricak H, Deasy J, Snyder A, Sala E. A novel representation of inter-site tumour heterogeneity from pre-treatment computed tomography textures classifies ovarian cancers by clinical outcome. European radiology 2017;27(9):3991-4001. https://doi.org/10.1007/s00330-017-4779-yCrossRefPubMedPubMedCentral

33.

Beer L, Martin-Gonzalez P, Delgado-Ortet M, Reinius M, Rundo L, Woitek R, Ursprung S, Escudero L, Sahin H, Funingana IG, Ang JE, Jimenez-Linan M, Lawton T, Phadke G, Davey S, Nguyen NQ, Markowetz F, Brenton JD, Crispin-Ortuzar M, Addley H, Sala E. Ultrasound-guided targeted biopsies of CT-based radiomic tumour habitats: technical development and initial experience in metastatic ovarian cancer. European radiology 2021;31(6):3765-3772. https://doi.org/10.1007/s00330-020-07560-8CrossRefPubMed

34.

Reinhold C, Rockall A, Sadowski EA, Siegelman ES, Maturen KE, Vargas HA, Forstner R, Glanc P, Andreotti RF, Thomassin-Naggara I. Ovarian-Adnexal Reporting Lexicon for MRI: A White Paper of the ACR Ovarian-Adnexal Reporting and Data Systems MRI Committee. Journal of the American College of Radiology : JACR 2021. https://doi.org/10.1016/j.jacr.2020.12.022CrossRefPubMed

35.

Sadowski EA, Thomassin-Naggara I, Rockall A, Maturen KE, Forstner R, Jha P, Nougaret S, Siegelman ES, Reinhold C. O-RADS MRI Risk Stratification System: Guide for Assessing Adnexal Lesions from the ACR O-RADS Committee. Radiology 2022;303(1):35-47. https://doi.org/10.1148/radiol.204371CrossRefPubMed

36.

Campbell SP, Baras AS, Ball MW, Kates M, Hahn NM, Bivalacqua TJ, Johnson MH, Pomper MG, Allaf ME, Rowe SP, Gorin MA. Low levels of PSMA expression limit the utility of (18)F-DCFPyL PET/CT for imaging urothelial carcinoma. Annals of nuclear medicine 2018;32(1):69-74. https://doi.org/10.1007/s12149-017-1216-xCrossRefPubMed

37.

Rhee H, Blazak J, Tham CM, Ng KL, Shepherd B, Lawson M, Preston J, Vela I, Thomas P, Wood S. Pilot study: use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour. EJNMMI research 2016;6(1):76. https://doi.org/10.1186/s13550-016-0231-6CrossRefPubMedPubMedCentral

38.

Meyer AR, Carducci MA, Denmeade SR, Markowski MC, Pomper MG, Pierorazio PM, Allaf ME, Rowe SP, Gorin MA. Improved identification of patients with oligometastatic clear cell renal cell carcinoma with PSMA-targeted (18)F-DCFPyL PET/CT. Annals of nuclear medicine 2019;33(8):617-623. https://doi.org/10.1007/s12149-019-01371-8CrossRefPubMedPubMedCentral

39.

Verma P, Malhotra G, Goel A, Rakshit S, Chandak A, Chedda R, Banerjee S, Asopa RV. Differential Uptake of 68Ga-PSMA-HBED-CC (PSMA-11) in Low-Grade Versus High-Grade Gliomas in Treatment-Naive Patients. Clinical nuclear medicine 2019;44(5):e318-e322. https://doi.org/10.1097/rlu.0000000000002520CrossRefPubMed

40.

Sathekge M, Lengana T, Modiselle M, Vorster M, Zeevaart J, Maes A, Ebenhan T, Van de Wiele C. (68)Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients. European journal of nuclear medicine and molecular imaging 2017;44(4):689-694. https://doi.org/10.1007/s00259-016-3563-6CrossRefPubMed

41.

Kirchner J, Schaarschmidt BM, Sawicki LM, Heusch P, Hautzel H, Ermert J, Rabenalt R, Antoch G, Buchbender C. Evaluation of Practical Interpretation Hurdles in 68Ga-PSMA PET/CT in 55 Patients: Physiological Tracer Distribution and Incidental Tracer Uptake. Clinical nuclear medicine 2017;42(7):e322-e327. https://doi.org/10.1097/rlu.0000000000001672CrossRefPubMed

42.

Heck MM, Tauber R, Schwaiger S, Retz M, D'Alessandria C, Maurer T, Gafita A, Wester HJ, Gschwend JE, Weber WA, Schwaiger M, Knorr K, Eiber M. Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with (177)Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer. European urology 2019;75(6):920-926. https://doi.org/10.1016/j.eururo.2018.11.016CrossRefPubMed

43.

Van de Wiele C, Sathekge M, de Spiegeleer B, De Jonghe PJ, Debruyne PR, Borms M, Beels L, Maes A. PSMA expression on neovasculature of solid tumors. Histology and histopathology 2020;35(9):919-927. https://doi.org/10.14670/hh-18-215

44.

Wu JB, Tang YL, Liang XH. Targeting VEGF pathway to normalize the vasculature: an emerging insight in cancer therapy. OncoTargets and therapy 2018;11:6901-6909. https://doi.org/10.2147/ott.s172042CrossRefPubMedPubMedCentral

45.

Grant CL, Caromile LA, Ho V, Durrani K, Rahman MM, Claffey KP, Fong GH, Shapiro LH. Prostate specific membrane antigen (PSMA) regulates angiogenesis independently of VEGF during ocular neovascularization. PloS one 2012;7(7):e41285. https://doi.org/10.1371/journal.pone.0041285

46.

Vangestel C, Van de Wiele C, Van Damme N, Staelens S, Pauwels P, Reutelingsperger CP, Peeters M. (99)mTc-(CO)(3) His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2011;52(11):1786-1794. https://doi.org/10.2967/jnumed.111.092650CrossRefPubMed

Titel: Distribution of prostate specific membrane antigen (PSMA) on PET-MRI in patients with and without ovarian cancer
verfasst von: Elizabeth A. Sadowski
Brittany Lees
Alan B. McMillian
Joanna E. Kusmirek
Steve Y. Cho
Lisa M. Barroilhet
Publikationsdatum: 01.06.2023
Verlag: Springer US
Erschienen in: Abdominal Radiology / Ausgabe 12/2023
Print ISSN: 2366-004X
Elektronische ISSN: 2366-0058
DOI: https://doi.org/10.1007/s00261-023-03957-3

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Distribution of prostate specific membrane antigen (PSMA) on PET-MRI in patients with and without ovarian cancer