Потенциал ПСМА-таргетной визуализации опухолей различных локализаций

Диагностика и терапия злокачественных новообразований в современной онкологии все больше ориентируется на использование молекулярных мишеней, участвующих в многостадийном процессе патогенеза опухолей. Простат-специфический мембранный антиген (ПСМА) является на сегодняшний день одним из таких молекулярных маркеров для рака предстательной железы, и в течение последних двух десятилетий отмечается активное развитие ПСМА-тераностики опухолей простаты. Однако многочисленные исследования последних лет показали, что ПСМА, несмотря на свое название, не является специфичным молекулярным маркером только для ткани предстательной железы. Выявлено, что экспрессия этого рецептора в других новообразованиях ассоциирована в большей степени с неоваскулярным эндотелием, что послужило началу исследований по клиническому применению ПСМА-направленной визуализации опухолей различных локализаций.

В данной лекции проанализированы возможности применения ПСМА-направленной радионуклидной диагностики, главным образом методов позитронной эмиссионной томографии, для различных гистологических вариантов неоплазий, а также особенности ПСМА-экспрессии некоторых опухолей. Авторы лекции демонстрируют существующие клинические примеры не только результатов диагностических исследований, но в ряде случаев и применения таргетной радионуклидной терапии. В лекции представлены возможные точки приложения ПСМА-направленных методов визуализации с точки зрения получения дополнительной информации об особенностях течения опухолевого процесса.

1. Horoszewicz J.S., Kawinski E., Murphy G.P. Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res. 1987;7(5B): 927–935.

2. Israeli R.S., Powell C.T., Corr J.G., Fair W.R., Heston W.D. Expression of the prostate-specific membrane antigen. Cancer Res. 1994;54(7):1807–1811.

3. Haberkorn U., Eder M., Kopka K., Babich J.W., Eisenhut M. New strategies in prostate cancer: Prostate Specific Membrane Antigen (PSMA) ligands for diagnosis and therapy. Clin. Cancer Res. 2016;22(1):9–15. DOI: 10.1158/1078-0432.CCR-150820.

4. Wang X., Tsui B., Ramamurthy G., Zhang P., Meyers J., Kenney M.E. et al. Theranostic agents for photodynamic therapy of prostate cancer by targeting prostate-specific membrane antigen. Mol. Cancer Ther. 2016;15(8):1834–1844. DOI: 10.1158/1535-7163.MCT-15-0722.

5. Bacich D.J., Ramadan E., O’Keefe D.S., Bukhari N., Wegorzewska I., Ojeifo O. et al. Deletion of the glutamate carboxypeptidase II gene in mice reveals a second enzyme activity that hydrolyzes N-acetylaspartylglutamate. J. Neurochem. 2002;83(1):20–29. DOI: 10.1046/j.1471-4159.2002.01117.x.

6. Чехонин В.П., Григорьев М.Э., Жирков Ю.А., Лебедев Д.В. Простатический специфический мембранный антиген и его роль в диагностике рака предстательной железы. Вопросы медицинской химии. 2002;48:31–43.

7. Chang S.S. Overview of prostate-specific membrane antigen. Reviews in Urology. 2004;6(10):13–18.

8. Bouchelouche K., Choyke P.L., Capala J. Prostate specific membrane antigen – a target for imaging and therapy with radionuclides. Discov. Med. 2010;9(44):55–61.

9. Farolfi A., Fendler W., Iravani A., Haberkorn U., Hicks R., Herrmann K. et al. Theranostics for advanced prostate cancer: current indications and future developments. Eur. Urol. Oncol. 2019;2:152–162. DOI: 10.1016/j.euo.2019.01.001.

10. 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(4):688–697. DOI: 10.1021/bc200279b.

11. Чернов В.И., Медведева А.А., Синилкин И.Г., Зельчан Р.В., Брагина О.Д. Разработка радиофармпрепаратов для радионуклидной диагностики в онкологии. Медицинская визуализация. 2016;2:63–66.

12. Медведева А.А., Чернов В.И., Зельчан Р.В., Рыбина А.Н., Брагина О.Д., Зебзеева О.С. Безопасность применения, фармакокинетика и дозиметрические характеристики радиофармацевтического препарата [99mTс]Tc-HYNICПСМА. Вопросы онкологии. 2025;71(1):117–127. DOI: 10.37469/0507-3758-2025-71-1-OF-2175.

13. Wester H.-J., Schottelius M. PSMA-targeted radiopharmaceuticals for imaging and therapy. Semin. Nucl. Med. 2019;49:302–312. DOI: 10.1053/j.semnuclmed.2019.02.008.

14. Rizzo A., Dall’Armellina S., Pizzuto D.A., Perotti G., Zagaria L., Lanni V. et al. PSMA radioligand uptake as a biomarker of neoangiogenesis in solid tumours: diagnostic or theragnostic factor? Cancers. 2022;14:4039. DOI: 10.3390/cancers14164039.

15. Silver D.A., Pellicer I., Fair W.R., Heston W.D., CordonCardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin. Cancer Res. 1997;3:81–85.

16. Spatz S., Tolkach Y., Jung K., Stephan C., Busch J., Ralla B. et al. Comprehensive evaluation of prostate-specific membrane antigen expression in the vasculature of renal tumors: implications for imaging studies and prognostic role. J. Urol. 2018;199(2):370–377. DOI: 10.1016/j.juro.2017.08.079.

17. McLeod D.S.A., Zhang L., Durante C., Cooper D.S. Contemporary debates in adult papillary thyroid cancer management. Endocr. Rev. 2019;40:1481–1499. DOI: 10.1210/er.201900085.

18. Haugen B.R., Alexander E.K., Bible K.C., Doherty G.M., Mandel S.J., Nikiforov Y.E. et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1–133. DOI: 10.1089/thy.2015.0020.

19. Fugazzola L., Elisei R., Fuhrer D., Jarzab B., Leboulleux S., Newbold K. et al. 2019 European Thyroid Association Guidelines for the Treatment and Follow-Up of Advanced Radioiodine-Refractory Thyroid Cancer. Eur. Thyroid J. 2019;8:227– 245. DOI: 10.1159/000502229.

20. Eisenhauer E.А., Therasse P., Bogaerts J., Schwartz L.H., Sargent D., Ford R. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer. 2009;45:228–247. DOI: 10.1016/j.ejca.2008.10.026.

21. Treglia G., Goichot B., Giovanella L., Hindié E., Jha A., Pacak K. et al. Prognostic and predictive value of nuclear imaging in endocrine oncology. Endocrine. 2020;67:9–19. DOI: 10.1007/s12020-019-02131-4.

22. Piccardo A., Trimboli P., Foppiani L., Treglia G., Ferrarazzo G., Massollo M. et al. PET/CT in thyroid nodule and differentiated thyroid cancer patients. The evidence-based state of the art. Rev. Endocr. Metab. Disord. 2019;20:47–64. DOI: 10.1007/s11154-019-09491-2.

23. Моисеенко В.М., Гладков О.М., Стенина М.Б., Деньгина Н.В., Карабина Е.В., Плыкина А.А. Практические рекомендации Российского общества клинической онкологии. 2024;14 (3s2).

24. Cabanillas M.E., Ryder M., Jimenez C. Targeted therapy for advanced thyroid cancer: kinase inhibitors and beyond. Endocr. Rev. 2019;40:1573–1604. DOI: 10.1210/er.2019-00007

25. Haddad R.I., Nasr C., Bischoff L., Busaidy N.L., Byrd D., Callender G. et al. NCCN guidelines insights: thyroid carcinoma, version 2. 2018. J. Natl. Compr. Cancer Netw. 2018;16:1429–1440. DOI: 10.6004/jnccn.2018.0089.

26. Elia G., Patrizio A., Ragusa F., Paparo S.R., Mazzi V., Balestri E. et al. Molecular features of aggressive thyroidcancer. Front. Oncol. 2022;12:1099280. DOI: 10.3389/fonc.2022.1099280.

27. Schlumberger M., Tahara M., Wirth L.J., Robinson B., Brose M.S., Elisei R. et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N. Engl. J. Med. 2015;372:621–630. DOI: 10.1056/NEJMoa1406470

28. Moore M., Panjwani S., Mathew R., Crowley M., Liu Y.-F., Aronova A. et al. Well-differentiated thyroid cancer neovasculature expresses prostate-specific membrane antigen-a possible novel therapeutic target. Endocr. Pathol. 2017;28:339–344. DOI: 10.1007/s12022-017-9500-9.

29. Sollini M., di Tommaso L., Kirienko M., Piombo C., Erreni M., Lania A.G. et al. PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome. EJNMMI Res. 2019;9:93. DOI: 10.1186/s13550-019-0559-9

30. Heitkötter B., Steinestel K., Trautmann M., Grünewald I., Barth P., Gevensleben H. et al. Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid. Oncotarget. 2018;9:9867–9874. DOI: 10.18632/oncotarget.23984.

31. Herrmann G., Schumm-Draeger P.M., Muller C., Atai E., Wenzel B., Fabian T. et al. T-lymphocytes, CD68-positive cells and vascularisation in thyroid carcinomas. J. Cancer Res. Clin. Oncol. 1994;120:651–656. DOI: 10.1007/BF01245376.

32. Lutje S., Gomez B., Cohnen J., Umutlu L., Gotthardt M., Poeppel T.D. et al. Imaging of prostate-specific membrane antigen expression in metastatic differentiated thyroid cancer using 68Ga-HBED-CC-PSMA PET/CT. Clin. Nucl. Med. 2017;42:20–25. DOI: 10.1097/RLU.0000000000001454.

33. Lawhn-Heath C., Yom S.S., Liu C., Villanueva-Meyer J.E., Aslam M., Smith R. et al. Gallium-68 prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) PET for imaging of thyroid cancer: A feasibility study. EJNMMI Res. 2020;10:128. DOI: 10.1186/s13550-020-00720-3.

34. Verma P., Malhotra G., Meshram V., Chandak A., Sonavane S., Lila A.R. et al. Prostate-specific membrane antigen expression in patients with differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy using 68Ga-PSMA-HBED-CC PET/CT. Clin. Nucl. Med. 2021;46:e406–e409. DOI: 10.1097/RLU.0000000000003655.

35. Wachter S., Di Fazio P., Maurer E., Manoharan J., Keber C., Pfestroff A. et al. Prostate-specific membrane antigen in anaplastic and poorly differentiated thyroid cancer – a new diagnostic and therapeutic target? Cancers. 2021;13:5688. DOI: 10.3390/cancers13225688.

36. De Vries L.H., Lodewijk L., Braat A.J.A.T., Krijger G.C., Valk G.D., Lam M.G.E.H. et al. 68Ga-PSMA PET/CT in radioactive iodine-refractory differentiated thyroid cancer and first treatment results with 177Lu-PSMA-617. EJNMMI Res. 2020;10:18. DOI: 10.1186/s13550-020-0610-x.

37. Pitalua-Cortes Q., Garcнa-Perez F.O., Vargas-Ahumada J., Gonzalez-Rueda S., Gomez-Argumosa E., Ignacio-Alvarez E. et al. Head-to-head Comparison of 68Ga-PSMA-11 and 131I in the follow-up of well-differentiated metastatic thyroid cancer: a new potential theragnostic agent. Front. Endocrinol. 2021;12:794759. DOI: 10.3389/fendo.2021.794759.

38. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer statistics, 2022. CA A Cancer J. Clin. 2022;72:7–33. DOI: 10.3322/caac.21708.

39. Capitanio U., Bensalah K., Bex A., Boorjian S.A., Bray F., Coleman J. et al. Epidemiology of renal cell carcinoma. Eur. Urol. 2019;75:74–84. DOI: 10.1016/j.eururo.2018.08.036.

40. Srinivasan R., Ricketts C.J., Sourbier C., Linehan W.M. New strategies in renal cell carcinoma: targeting the genetic and metabolic basis of disease. Clin. Cancer Res. 2015;21:10–17. DOI: 10.1158/1078-0432.CCR-13-2993.

41. Heng D.Y., Xie W., Regan M.M., Warren M.A., Golshayan A.R., Sahi C. et al. Prognostic Factors for Overall Survival in Patients with Metastatic Renal Cell Carcinoma Treated with Vascular Endothelial Growth Factor – Targeted Agents: Results from a Large, Multicenter Study. J. Clin. Oncol. 2009;27:5794–5799. DOI: 10.1200/JCO.2008.21.4809.

42. Tyson M.D., Chang S.S. Optimal surveillance strategies after surgery for renal cell carcinoma. J. Natl. Compr. Cancer Netw. 2017;15:835–840. DOI: 10.6004/jnccn.2017.0102.

43. Lindenberg L., Mena E., Choyke P.L., Bouchelouche K. PET imaging in renal cancer. Curr. Opin. Oncol. 2019;31:216–221. DOI: 10.1097/CCO.0000000000000518.

44. Motzer R.J., Jonasch E., Agarwal N., Alva A., Baine M., Beckermann K. et al. Kidney cancer, version 3.2022, nccn clinical practice guidelines in oncology. J. Natl. Compr. Cancer Netw. 2022;20:71–90. DOI: 10.6004/jnccn.2022.0001.

45. Escudier B., Porta C., Schmidinger M., Rioux-Leclercq N., Bex A., Khoo V. et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2019;30:706–720. DOI: 10.1093/annonc/mdz056.

46. Ljungberg B., Albiges L., Abu-Ghanem Y., Bedke J., Capitanio U., Dabestani S. et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur. Urol. 2022;82:399–410. DOI: 10.1016/j.eururo.2022.03.006.

47. Garg G., Benchekroun M.T., Abraham T. FDG-PET/CT in the postoperative period: utility, expected findings, complications, and pitfalls. Semin. Nucl. Med. 2017;47:579–594. DOI: 10.1053/j.semnuclmed.2017.07.005.

48. Chen R., Zhou X., Huang G., Liu J. Fructose 1,6-bisphosphatase 1 expression reduces 18F-FDG uptake in clear cell renal cell carcinoma. Contrast Media Mol. Imaging. 2019; 2019:9463926. DOI: 10.1155/2019/9463926.

49. Rhee H., Blazak J., Tham C.M., Ng K.L., Shepherd B., Lawson M. et al. Pilot study: Use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumor. EJNMMI Res. 2016;6:76. DOI: 10.1186/s13550-016-0231-6.

50. Gao J., Xu Q., Fu Y., He K., Zhang C., Zhang Q. et al. Comprehensive evaluation of 68Ga-PSMA-11 PET/CT parameters for discriminating pathological characteristics in primary clear-cell renal cell carcinoma. Eur. J. Nucl. Med. Mol. Imaging. 2021;48:561–569. DOI: 10.1007/s00259-020-04916-6.

51. Udovicich C., Callahan J., Bressel M., Ong W.L., Perera M., Tran B. et al. Impact of prostate-specific membrane antigen positron emission tomography/computed tomography in the management of oligometastatic renal cell carcinoma. Eur. Urol. Open Sci. 2022;44:60–68. DOI: 10.1016/j.euros.2022.08.001.

52. Li Y., Zheng R., Zhang Y., Huang C., Tian L., Liu R. et al. Special issue “The advance of solid tumor research in China”: 68Ga-PSMA-11 PET/CT for evaluating primary and metastatic lesions in different histological subtypes of renal cell carcinoma. Int. J. Cancer. 2023;152:42–50. DOI: 10.1002/ijc.34189.

53. Meyer A.R., Carducci M.A., Denmeade S.R., Markowski M.C., Pomper M.G., Pierorazio P.M. et al. Improved identification of patients with oligometastatic clear cell renal cell carcinoma with PSMA-targeted 18F-DCFPyL PET/CT. Ann. Nucl. Med. 2019;33:617–623. DOI: 10.1007/s12149-019-01371-8.

54. Raveenthiran S., Esler R., Yaxley J., Kyle S. The use of 68GaPET/CT PSMA in the staging of primary and suspected recurrent renal cell carcinoma. Eur. J. Nucl. Med. Mol. Imaging. 2019;46:2280–2288. DOI: 10.1007/s00259-019-04432-2.

55. Gühne F., Seifert P., Theis B., Steinert M., Freesmeyer M., Drescher R. PSMA-PET/CT in patients with recurrent clear cell renal cell carcinoma: histopathological correlations of imaging findings. Diagnostics. 2021;11:1142. DOI: 10.3390/diagnostics11071142.

56. Liu Y., Wang G., Yu H., Wu Y., Lin M., Gao J. et al. Comparison of 18F-DCFPyL and 18F-FDG PET/computed tomography for the restaging of clear cell renal cell carcinoma: Preliminary results of 15 patients. Nucl. Med. Commun. 2020;41:1299–1305. DOI: 10.1097/MNM.0000000000001285

57. Ильяков В.С., Пронин А.И., Парнас А.В., Субботин А.С., Крылов А.С., Гелиашвили Т.М. и др. ПЭТ/КТ с 18F-PSMA-1007 в диагностике первичного очага и местного рецидива светлоклеточного почечно-клеточного рака в сравнении с 18F-ФДГ: проспективное исследование. Онкологический журнал: лучевая диагностика, лучевая терапия. 2024;7(2):15–26. DOI: 10.37174/2587-7593-2024-7-2-15-26.

58. Ильяков В.С., Пронин А.И., Парнас А.В., Субботин А.С., Крылов А.С., Гелиашвили Т.М. и др. ПЭТ/КТ с 18F-PSMA-1007 в диагностике метастазов светлоклеточного почечно-клеточного рака в сравнении с 18F-ФДГ: проспективное исследование. Онкологический журнал: лучевая диагностика, лучевая терапия. 2024;7(3):41–47. DOI: 10.37174/2587-7593-2024-7-3-41-47.

59. Злокачественные новообразования в России в 2023 году (заболеваемость и смертность); под ред. А.Д. Каприна [и др.]. М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2024:276.

60. Клинические рекомендации Министерства здравоохранения Российской Федерации. 2021. URL: https://cr.minzdrav.gov.ru.

61. Kasoha M., Unger C., Solomayer E.F., Bohle R.M., Zaharia C., Khreich F. et al. Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases. Clin. Exp. Metastasis. 2017;34:479–490. DOI: 10.1007/s10585-018-9878-x.

62. Passah A., Arora S., Damle N.A., Tripathi M., Bal C., Subudhi T.K. et al. 68Ga – prostate-specific membrane antigen PET/CT in triple-negative breast cancer. Clin. Nucl. Med. 2018; 43: 460–461. DOI: 10.1097/RLU.0000000000002071.

63. Arslan E., Ergül N., Beyhan E., Erol Fenercioglu Ö., Sahin R., Cin M. et al. The roles of 68 Ga-PSMA PET/CT and 18 F-FDG PET/CT imaging in patients with triple-negative breast cancer and the association of tissue PSMA and claudin 1, 4, and 7 levels with PET findings. Nucl. Med. Commun. 2023;44:284–290. DOI: 10.1097/MNM.0000000000001663.

64. Marta G.N., Wimana Z., Taraji L., Critchi G., Aftimos P.G., Piccart-Gebhart M.J. et al. Prostate-specific membrane antigen (PSMA) expression in patients with metastatic triple negative breast cancer: Initial results of the PRISMA study. JCO. 2023;41:1025. DOI: 10.1200/JCO.2023.41.16_suppl.1025.

65. Парнас А.В., Оджарова А.А., Пронин А.И., Ильяков В.С., Мещерякова Н.А., Камолова З.Х. и др. Возможности ПЭТ/КТ с 18F-ПСМА-1007 в диагностике трижды негативного рака молочной железы: клинический случай. Онкологический журнал: лучевая диагностика, лучевая терапия. 2021;4(4):88–92. DOI: 10.37174/2587-7593-2021-4-4-88-92.

66. Wernicke A.G., Varma S., Greenwood E.A., Christos P.J., Chao K.S., Liu H. et al. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers. APMIS. 2014;122(6):482–489. DOI: 10.1111/apm.12195.

67. Tolkach Y., Gevensleben H., Bundschuh R., Koyun A., Huber D., Kehrer C. et al. Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy. Breast Cancer Res. Treat. 2018;169(3):447–455. DOI: 10.1007/s10549-018-4717-y.

68. Andryszak N., Świniuch D., Wójcik E., Ramlau R., Ruchała M., Czepczyński R. Head-to-рead сomparison of [18F] PSMA-1007 and [18F]FDG PET/CT in patients with triple-negative breast cancer. Cancers (Basel). 2024;16(3):667. DOI: 10.3390/cancers16030667.

69. Zárate-García C.D., Cardoza-Ochoa D.R., SánchezVera Y., González-Díaz J.I. Incidental diagnosis of metastatic breast cancer in a man With 99m Tc-PSMA SPECT/CT. Clin Nucl Med. 2023;48(4):e163-e164. DOI: 10.1097/RLU.0000000000004549.

70. Llovet J.M., Kelley R.K., Villanueva A., Singal A.G., Pikarsky E., Roayaie S. et al. Hepatocellular carcinoma. Nat. Rev. Dis. Prim. 2021;7:6. DOI: 10.1038/s41572-020-00240-3.

71. McGlynn K.A., Petrick J.L., London W.T. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin. Liver Dis. 2015; 19:223–238. DOI: 10.1016/j.cld.2015.01.001.

72. Navin P., Venkatesh S. Hepatocellular carcinoma: state of the art imaging and recent advances. J. Clin. Transl. Hepatol. 2019;28:72–85. DOI: 10.14218/JCTH.2018.00032.

73. Sharma B., Martin A., Zerizer I. Positron emission tomography-computed tomography in liver imaging. Semin. Ultrasound CT MR. 2013;34:66–80. DOI: 10.1053/j.sult.2012.11.006.

74. Kesler M., Levine C., Hershkovitz D., Mishani E., Menachemn Y., Lerman H. et al. 68Ga-PSMA is a novel PET-CT tracer for imaging of hepatocellular carcinoma: A prospective study. J. Nucl. Med. 2018. DOI: 10.2967/jnumed.118.214833.

75. 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;44:702–706. DOI: 10.1097/RLU.0000000000002701.

76. Kunikowska J., Cieślak B., Gierej B., Patkowski W., Kraj L., Kotulski M. et al. [68 Ga]Ga-prostate-specific membrane antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma. Eur. J. Nucl. Med. Mol. Imaging. 2021;48:883–892. DOI: 10.1007/s00259-020-05017-0.

77. Gündoğan C., Ergül N., Çakır M.S., Kılıçkesmez Ö., Gürsu R.U., Aksoy T. et al. 68Ga-PSMA PET/CT Versus 18F-FDG PET/CT for imaging of hepatocellular carcinoma. Mol. Imaging Radionucl. Ther. 2021;30:79–85. DOI: 10.4274/mirt.galenos.2021.92053.

78. Hirmas N., Leyh C., Sraieb M., Barbato F., Schaarschmidt B.M., Umutlu L. et al. 68Ga-PSMA-11 PET/CT Improves Tumor Detection and Impacts Management in Patients with Hepatocellular Carcinoma. J. Nucl. Med. 2021;62:1235–1241. DOI: 10.2967/jnumed.120.257915

79. Thompson S.M., Suman G., Torbenson M.S., Chen Z.-M.E., Jondal D.E., Patra A. et al. PSMA as a theranostic target in hepatocellular carcinoma: immunohistochemistry and 68 Ga-PSMA-11 PET using cyclotron-produced 68Ga. Hepatol. Commun. 2022;6:1172–1185. DOI: 10.1002/hep4.1861.

80. Denmeade S.R., Mhaka A.M., Rosen D.M., Brennen W.N., Dalrymple S., Dach I. et al. Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy. Sci. Transl. Med. 2012;4(140):140ra86. DOI: 10.1126/scitranslmed.3003886.

81. Lu Q., Long Y., Gai Y., Liu Q., Jiang D., Lan X. [(177) Lu]Lu-PSMA-617 theranostic probe for hepatocellular carcinoma imaging and therapy. Eur. J. Nucl. Med. Mol. Imaging. 2023;50(8):2342–2352. DOI: 10.1007/s00259-023-06155-x.

82. Чернов В.И., Дудникова Е.А., Гольдберг В.Е., Кравчук Т.Л., Данилова А.В., Зельчан Р.В. и др. Позитронная эмиссионная томография в диагностике и мониторинге лимфопролиферативных заболеваний. Медицинская радиология и радиационная безопасность. 2018;63(6):41–50. DOI: 10.12737/article_5c0b8d72a8bb98.40545646.

83. Weiler-Sagie M., Bushelev O., Epelbaum R., Dann E.J., Haim N., Avivi I. et al. (18)F-FDG avidity in lymphoma readdressed: a study of 766 patients. J. Nucl. Med. 2010;51: 25–30. DOI: 10.2967/jnumed.109.067892.

84. Calvo-Vidal M.N., Cerchietti L. The metabolism of lymphomas. Curr. Opin. Hematol. 2013;20:345–354. DOI: 10.1097/MOH.0b013e3283623d16.

85. Kanthan G.L., Coyle L., Kneebone A., Schembri G.P., Hsiao E. Follicular lymphoma showing avid uptake on 68Ga PSMA-HBED-CC PET/CT. Clin. Nucl. Med. 2016;41(6): 500–501. DOI: 10.1097/RLU.0000000000001169.

86. Miceli A., Riondato M., D’Amico F., Donegani M.I., Piol N., Mora M. et al. Concomitant prostate cancer and hodgkin lymphoma: a differential diagnosis guided by a combined 68Ga-PSMA-11 and 18F-FDG PET/CT Approach. Medicina (Kaunas). 2021;57(9):975. DOI: 10.3390/medicina57090975.

87. Dhiantravan N., Hovey E., Bosco A., Wegner E.A. Concomitant prostate carcinoma and follicular lymphoma: “flip-flop” appearances on PSMA and FDG PET/CT scans. Clin. Nucl. Med. 2019;44(10):797–798. DOI: 10.1097/RLU.0000000000002727.

88. Caputo S.A., Jang A., Talbert J., Saba N.S., Sartor O. Prostate-specific membrane antigen PET positivity in a lung mass: diagnosis of diffuse large B-cell lymphoma. Clin. Nucl. Med. 2023;48(2):190–191. DOI: 10.1097/RLU.0000000000004503.

89. Vamadevan S., Le K., Bui C., Mansberg R. Prostate-specific membrane antigen uptake in small cleaved b-cell follicular non-hodgkin lymphoma. Clin Nucl Med. 2016 Dec; 41(12):980–981. DOI: 10.1097/RLU.0000000000001378.

90. Milrod C.J., Brown C., Mega A.E. Increased PSMA-targeted 18 F-DCFPyL uptake in peripheral T-cell lymphoma. Clin. Nucl. Med. 2024;49(7):e338-e339. DOI: 10.1097/RLU.0000000000005264.

91. De Souza S.P.M., Tobar N., Frasson F., Perini E.A., de Souza C.A., Delamain M.T. et al. Head-to-head comparison between 68Ga-PSMA and 18F-FDG-PET/CT in lymphomas: a preliminary analysis. Nucl. Med. Commun. 2021;42(12):1355–1360. DOI: 10.1097/MNM.0000000000001465.

92. Vuijk F.A., Kleiburg F., Noortman W.A, Heijmen L., Shahbazi S.F., van Velden F.H.P. et al. Prostate-specific membrane antigen targeted Pet/CT imaging in patients with colon, gastric and pancreatic cancer. Cancers. 2022;14:6209. DOI: 10.3390/cancers14246209.

93. Jain R. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62. DOI: 10.1126/science.1104819.

94. Vangestel C., Van de Wiele C., Van Damme N., Staelens S., Pauwels P., Reutlingsperger C. et al. 99mTc-(CO)3 His-Annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab. J. Nucl. Med. 2011;526:1786–1794. DOI: 10.2967/jnumed.111.092650.

95. Grant C., Caromile L., Ho V., Durrani K., Rahman M., Claffey K. et al. Prostate specific membrane antigen (PSMA) regulates angiogenesis independently of VEGF during ocular neovascularization. PLoS One. 2012;7:e41285. DOI: 10.1371/journal.pone.0041285.

96. Rahbar K., Ahmadzadehfar H., Kratochwil C., Haberkorn U., Schäfers M., Essler M. et al. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J. Nucl. Med. 2017;58(1):85–90. DOI: 10.2967/jnumed.116.183194.

97. Rahbar K., Boegemann M., Yordanova A., Eveslage M., Schäfers M., Essler M. et al. PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival. Eur. J. Nucl. Med. Mol. Imaging. 2018;45(1):12–19. DOI: 10.1007/s00259-017-3848-4.

98. Yordanova A., Linden P., Hauser S., Meisenheimer M., Kürpig S., Feldmann G. et al. Outcome and safety of rechallenge [177Lu]Lu-PSMA-617 in patients with metastatic prostate cancer. Eur. J. Nucl. Med. Mol. Imaging. 2019;46(5):1073– 1080. DOI: 10.1007/s00259-018-4222-x.

99. Khreish F., Kochems N., Rosar F., Sabet A., Ries M., Maus S. et al. Response and outcome of liver metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing 177Lu-PSMA-617 radioligand therapy. Eur. J. Nucl. Med. Mol. Imaging. 2021;48(1):103–112. DOI: 10.1007/s00259-020-04828-5.

100. Violet J., Sandhu S., Iravani A., Ferdinandus J., Thang S.P., Kong G. et al. Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA-617 Theranostics in Met astatic Castration-Resistant Prostate Cancer. J. Nucl. Med. 2020;61(6):857–865. DOI: 10.2967/jnumed.119.236414.

101. Sartor O., de Bono J., Chi K.N., Fizazi K., Herrmann K., Rahbar K. et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N. Engl. J. Med. 2021; 385(12):1091–1103. DOI: 10.1056/NEJMoa2107322.

102. Neri D., Bicknell R. Tumour vascular targeting. Nat. Rev. Cancer. 2005;5:436–446. DOI: 10.1038/nrc1627.

103. Seaman S., Stevens J., Yang M.Y., Logsdon D., Graff-Cherry C., St Croix B. Genes that distinguish physiological and pathological angiogenesis. Cancer Cell. 2007;11:539–54. DOI: 10.1016/j.ccr.2007.04.017.

104. St Croix B., Rago C., Velculescu V., Traverso G., Romans K.E., Montgomery E. et al. Genes expressed in human tumor endothelium. Science. 2000;289:1197202. DOI: 10.1126/science.289.5482.1197.