vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2025-2-54-59vtio-1891Research ArticleКлиническая трансплантологияClinical TransplantologyПЭТ-КТ c 18F-FMISO в диагностике гипоксии трансплантата печениAssessment of liver graft hypoxia via 18F-FMISO PET‑CT imagingТилеубергеновИ. И.TileubergenovI. I.

Тилеубергенов Инхат Ибрагимович, к.м.н. руководитель группы трансплантации отдела интервенционной радиологии и оперативной хирургии РНЦРХТ, хирург-трансплантолог

Санкт-Петербург

 

St. Petersburg

inkhat@mail.ruИвановаА. А.IvanovaA. A.

Санкт-Петербург

St. Petersburg

ДолбовА. Л.DolbovA. L.

Санкт-Петербург

St. Petersburg

ГерасимоваО. А.GerasimovaO. A.

Герасимова Ольга Анатольевна, д.м.н., вед. научный сотр. группы трансплантологии, руководитель амбулаторного центра трансплантологии

197758, Санкт-Петербург, ул. Ленинградская, 70

Olga A. Gerasimova

70, Leningradskaya str., St. Petersburg, 197758

ren321@mail.ruШералиевА. Р.SheralievA. R.

Санкт-Петербург

St. Petersburg

ЖуйковВ. Н.ZhuykovV. N.

Санкт-Петербург

St. Petersburg

ГрановД. А.GranovD. A.

Санкт-Петербург

St. Petersburg

ФГБУ «Российский научный центр радиологии и хирургических технологий имени академика А.М. Гранова» Минздрава РоссииРоссияRussian Research Center of Radiology and Surgical TechnologiesRussian Federation2025120720252725459Copyright © Тилеубергенов И.И., Иванова А.А., Долбов А.Л., Герасимова О.А., Шералиев А.Р., Жуйков В.Н., Гранов Д.А., 20252025Тилеубергенов И.И., Иванова А.А., Долбов А.Л., Герасимова О.А., Шералиев А.Р., Жуйков В.Н., Гранов Д.А.Tileubergenov I.I., Ivanova A.A., Dolbov A.L., Gerasimova O.A., Sheraliev A.R., Zhuykov V.N., Granov D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/1891Цель

Цель: на основании данных литературных источников и опыта применения радиофармпрепарата (РФП) 18F-FMISO в онкологии авторы пилотного исследования предприняли попытку оценить возможность не- инвазивной ПЭТ-КТ-диагностики выявлять гипоксию в трансплантате печени, развивающуюся вследствие ишемического реперфузионного повреждения (ИРП).

Материалы и методы

Материалы и методы. Поглощение РФП 18F-FMISO опухолями при ПЭТ-КТ дает количественную карту гипоксии, использование изображений гипоксии для управления лучевой терапией является областью активных исследований. В процессе отработки методики исследования впервые получены изображения накопления РФП в печени пациентки в отдаленном пери- оде после трансплантации печени.

Результаты

Результаты. За положительный результат исследования, т. е. наличие гипоксии трансплантата, принимали увеличение среднего и максимального SUV на 180-й минуте после введения внутривенного РФП по сравнению с 90-й минутой, получали две серии изображений: КТ и ПЭТ. Выявили диффузное накопление препарата в печени: на 180-й минуте обнаружена более сильная фиксация препарата в печени относительно фона, чем на 90-й.

Заключение

Заключение. Полученные сведения позволяют пред- положить гипоксию трансплантата при отсутствии биохимических отклонений. Методика представляется перспективной для диагностики изменений в трансплантате печени, приводящих к гипоксии, но требует дальнейшего ее усовершенствования.

Objective

Objective: drawing on existing literature and the clinical use of radiopharmaceutical (RFP) 18F-FMISO in on- cology, this pilot study aims to assess the feasibility of using non-invasive PET-CT imaging to detect hypoxia in liver grafts resulting from ischemia-reperfusion injury.

Materials and methods

Materials and methods. 18F-FMISO uptake in tumors, as visualized by PET-CT, enables the generation of quantitative maps of tissue hypoxia, a technique that is increa- singly being explored to guide radiation therapy planning. As part of refining the study methodology, the research team successfully obtained the first PET-CT images demonstrating 18F-FMISO uptake in the liver of a patient at a late postoperative stage following liver transplantation.

Results

Results. A positive indication of transplant hypoxia was defined as an increase in both the mean and maximum standardized uptake values (SUVs) when measured at 180 minutes post-intravenous injection of the radiopharmaceutical, compared to measurements at 90 minutes. Two imaging series – CT and PET – were acquired. Diffuse uptake of the radiopharmaceutical was observed in the liver, with greater tracer retention relative to background at 180 minutes compared to 90 minutes post-injection.

Conclusion

Conclusion. The findings suggest the presence of transplant hypoxia despite the absence of biochemical abnor- malities. This technique shows promise as a non-invasive diagnostic tool for detecting hypoxic changes in liver grafts. However, further optimization and validation of the technique are necessary.

РФП 18F-FMISOтрансплантат печениПЭТ-КТишемияреперфузия18F-FMISOradiopharmaceuticalliver transplantPET-CTischemia-reperfusion injuryReferencesDar WA, Sullivan E, Bynon JS, Eltzschig H, Ju C. Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms. Liver Int. 2019 May; 39 (5): 788–801. doi: 10.1111/liv.14091.Dar WA, Sullivan E, Bynon JS, Eltzschig H, Ju C. Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms. Liver Int. 2019 May; 39 (5): 788–801. doi: 10.1111/liv.14091.Zhai Y, Petrowsky H, Hong JC, Busuttil RW, KupiecWeglinski JW. Ischaemia-reperfusion injury in liver transplantation – from bench to bedside. Nat Rev Gastroenterol Hepatol. 2013 Feb; 10 (2): 79–89. doi: 10.1038/nrgastro.2012.225.Zhai Y, Petrowsky H, Hong JC, Busuttil RW, KupiecWeglinski JW. Ischaemia-reperfusion injury in liver transplantation – from bench to bedside. Nat Rev Gastroenterol Hepatol. 2013 Feb; 10 (2): 79–89. doi: 10.1038/nrgastro.2012.225.Man K, Fan ST, Lo CM, Liu CL, Fung PC, Liang TB et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression. Ann Surg. 2003 Feb; 237 (2): 256–264. doi: 10.1097/01.SLA.0000048976.11824.67.Man K, Fan ST, Lo CM, Liu CL, Fung PC, Liang TB et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression. Ann Surg. 2003 Feb; 237 (2): 256–264. doi: 10.1097/01.SLA.0000048976.11824.67.Esch JS, Jurk K, Knoefel WT, Roeder G, Voss H, Tustas RY et al. Platelet activation and increased tissue factor expression on monocytes in reperfusion injury following orthotopic liver transplantation. Platelets. 2010; 21 (5): 348–359. doi: 10.3109/09537101003739897.Esch JS, Jurk K, Knoefel WT, Roeder G, Voss H, Tustas RY et al. Platelet activation and increased tissue factor expression on monocytes in reperfusion injury following orthotopic liver transplantation. Platelets. 2010; 21 (5): 348–359. doi: 10.3109/09537101003739897.Miyashita T, Nakanuma S, Ahmed AK, Makino I, Hayashi H, Oyama K et al. Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation. Eur Surg. 2016; 48: 92–98. doi: 10.1007/s10353-015-0363-3.Miyashita T, Nakanuma S, Ahmed AK, Makino I, Hayashi H, Oyama K et al. Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation. Eur Surg. 2016; 48: 92–98. doi: 10.1007/s10353-015-0363-3.Liu J, Man K. Mechanistic Insight and Clinical Implications of Ischemia/Reperfusion Injury Post Liver Transplantation. Cell Mol Gastroenterol Hepatol. 2023; 15 (6): 1463–1474. doi: 10.1016/j.jcmgh.2023.03.003.Liu J, Man K. Mechanistic Insight and Clinical Implications of Ischemia/Reperfusion Injury Post Liver Transplantation. Cell Mol Gastroenterol Hepatol. 2023; 15 (6): 1463–1474. doi: 10.1016/j.jcmgh.2023.03.003.Golse N, Guglielmo N, El Metni A, Frosio F, Cosse C, Naili S et al. Arterial Lactate Concentration at the End of Liver Transplantation Is an Early Predictor of Primary Graft Dysfunction. Ann Surg. 2019 Jul; 270 (1): 131– 138. doi: 10.1097/SLA.0000000000002726.Golse N, Guglielmo N, El Metni A, Frosio F, Cosse C, Naili S et al. Arterial Lactate Concentration at the End of Liver Transplantation Is an Early Predictor of Primary Graft Dysfunction. Ann Surg. 2019 Jul; 270 (1): 131– 138. doi: 10.1097/SLA.0000000000002726.Моисеенко АВ, Поликарпов АА, Таразов ПГ, Гранов ДА. Первый опыт прямого перфузионного исследования трансплантата после ортотопической пересадки печени. Вестник трансплантологии и искусственных органов. 2020; 22 (3): 99–106. https://doi.org/10.15825/1995-1191-2020-3-99-106.Moiseenko AV, Polikarpov AA, Tarazov PG, Granov DA. Initial experience in direct graft perfusion assessment following orthotopic liver transplant. Russian Journal of Transplantology and Artificial Organs. 2020; 22 (3): 99–106. https://doi.org/10.15825/1995-1191-2020-3-99-106.Rajendran JG, Mankoff DA, O’Sullivan F, Peterson LM, Schwartz DL, Conrad EU et al. Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res. 2004 Apr 1; 10 (7): 2245–2252. doi: 10.1158/1078-0432.ccr0688-3.Rajendran JG, Mankoff DA, O’Sullivan F, Peterson LM, Schwartz DL, Conrad EU et al. Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res. 2004 Apr 1; 10 (7): 2245–2252. doi: 10.1158/1078-0432.ccr0688-3.Zschaeck S, Steinbach J, Troost EG. FMISO as a Biomarker for Clinical Radiation Oncology. Recent Results Cancer Res. 2016; 198: 189–201. doi: 10.1007/978-3-662-49651-0_10.Zschaeck S, Steinbach J, Troost EG. FMISO as a Biomarker for Clinical Radiation Oncology. Recent Results Cancer Res. 2016; 198: 189–201. doi: 10.1007/978-3-662-49651-0_10.Masaki Y, Shimizu Y, Yoshioka T, Tanaka Y, Nishijima K, Zhao S et al. The accumulation mechanism of the hypoxia-imaging probe «FMISO» by imaging mass spectrometry: possible involvement of low-molecular metabolites. Sci Rep. 2015 Nov 19; 5: 16802. doi: 10.1038/srep16802.Masaki Y, Shimizu Y, Yoshioka T, Tanaka Y, Nishijima K, Zhao S et al. The accumulation mechanism of the hypoxia-imaging probe «FMISO» by imaging mass spectrometry: possible involvement of low-molecular metabolites. Sci Rep. 2015 Nov 19; 5: 16802. doi: 10.1038/srep16802.Sorace AG, Elkassem AA, Galgano SJ, Lapi SE, Larimer BM, Partridge SC et al. Imaging for Response Assessment in Cancer Clinical Trials. Semin Nucl Med. 2020 Nov; 50 (6): 488–504. doi: 10.1053/j.semnuclmed.2020.05.001.Sorace AG, Elkassem AA, Galgano SJ, Lapi SE, Larimer BM, Partridge SC et al. Imaging for Response Assessment in Cancer Clinical Trials. Semin Nucl Med. 2020 Nov; 50 (6): 488–504. doi: 10.1053/j.semnuclmed.2020.05.001.Abdo R-alla, Lamare F, Allard M, Fernandez P, Bentourkia M. Delineation techniques of tumor hypoxia volume with 18F-FMISO PET imaging. IEEE Nuclear Science Symposium and Medical Imaging Conference Proceedings (NSS/MIC). 2018: 1–5. doi: 10.1109/NSSMIC.2018.8824757.Abdo R-alla, Lamare F, Allard M, Fernandez P, Bentourkia M. Delineation techniques of tumor hypoxia volume with 18F-FMISO PET imaging. IEEE Nuclear Science Symposium and Medical Imaging Conference Proceedings (NSS/MIC). 2018: 1–5. doi: 10.1109/NSSMIC.2018.8824757.Lopes S, Ferreira S, Caetano M. PET/CT in the Evaluation of Hypoxia for Radiotherapy Planning in Head and Neck Tumors: Systematic Literature Review. J Nucl Med Technol. 2021 Jun; 49 (2): 107–113. doi: 10.2967/jnmt.120.249540.Lopes S, Ferreira S, Caetano M. PET/CT in the Evaluation of Hypoxia for Radiotherapy Planning in Head and Neck Tumors: Systematic Literature Review. J Nucl Med Technol. 2021 Jun; 49 (2): 107–113. doi: 10.2967/jnmt.120.249540.Wray R, Mauguen A, Michaud L, Leithner D, Yeh R, Riaz N et al. Development of 18F-Fluoromisonidazole Hypoxia PET/CT Diagnostic Interpretation Criteria and Validation of Interreader Reliability, Reproducibility, and Performance. J Nucl Med. 2024 Oct 1; 65 (10): 1526–1532. doi: 10.2967/jnumed.124.267775. PMID: 39266287; PMCID: PMC11448606.Wray R, Mauguen A, Michaud L, Leithner D, Yeh R, Riaz N et al. Development of 18F-Fluoromisonidazole Hypoxia PET/CT Diagnostic Interpretation Criteria and Validation of Interreader Reliability, Reproducibility, and Performance. J Nucl Med. 2024 Oct 1; 65 (10): 1526–1532. doi: 10.2967/jnumed.124.267775. PMID: 39266287; PMCID: PMC11448606.Jagtap R, Asopa RV, Basu S. Evaluating cardiac hypoxia in hibernating myocardium: Comparison of 99mTc MIBI/18F-fluorodeoxyglucose and 18F-fluoromisonidazole positron emission tomography-computed tomography in relation to normal, hibernating, and infarct myocardium. World J Nucl Med. 2019 Jan-Mar; 18 (1): 30–35. doi: 10.4103/wjnm.WJNM_16_18. PMID: 30774543; PMCID: PMC6357711.Jagtap R, Asopa RV, Basu S. Evaluating cardiac hypoxia in hibernating myocardium: Comparison of 99mTc MIBI/18F-fluorodeoxyglucose and 18F-fluoromisonidazole positron emission tomography-computed tomography in relation to normal, hibernating, and infarct myocardium. World J Nucl Med. 2019 Jan-Mar; 18 (1): 30–35. doi: 10.4103/wjnm.WJNM_16_18. PMID: 30774543; PMCID: PMC6357711.

The authors declare that there are no conflicts of interest present.