Применение гибридных радионуклидных технологий визуализации и радионуклидной терапии у больных с остеогенной саркомой

Цель: Продемонстрировать возможности различных гибридных методов исследования костной системы в диагностике первичного очага и метастазов остеосаркомы. Познакомить специалистов с перспективой применения радионуклидной терапии в лечении больных с остеосаркомой.

Материал и методы: Материал составили наиболее демонстративные случаи из клинической практики НМИЦ онкологии им. Н.Н. Блохина Минздрава России.

Результаты: Приведённые примеры показали необходимость привлечения всех возможных радионуклидных модальностей для диагностики и, особенно, мониторинга больных с остеосаркомой для более раннего выявления рецидивов и метастазов.

Выводы: Более широкое использование современных гибридных методов исследования (ОФЭКТ/КТ и ПЭТ/КТ) позволяет расширить возможности более раннего выявления метастазов остеосаркомы не только в костях, но и в других органах и тканях.

1. Mebarki M, Medjahedi A, Menemani A, et al. Osteosarcoma pulmonary metastasis mimicking abnormal skeletal uptake in bone scan: utility of SPECT/CT. Clinical Nuclear Medicine. 2013;38(10):392-4.

2. Delbeke D, Coleman RE, Guiberteau MJ, et al. Procedure Guideline for SPECT/CT Imaging 1.0. J Nucl Med. 2006;47:1227-34.

3. Behzadi AH, Raza SI, Carrino JA, et al. Applications of PET/ CT and PET/MR Imaging in Primary Bone Malignancies. PET Clin. 2018 Oct; 13(4):623-34. Published online 2018 Aug 17. https://doi.org/10.1016/j.cpet.2018.05.012

4. Hongtao L, Hui Z, Bingshun W, et al. 18F-FDG positron emission tomography for the assessment of histological response to neoadjuvant chemotherapy in osteosarcomas: A meta-analysis. Surg Oncol. 2012;21:165-70.

5. Bajpai J, Kumar R, Sreenivas V, et al. Prediction of chemotherapy response by PET-CT in osteosarcoma: Correlation with histologic necrosis. J Pediatr Hematol Oncol. 2011;33:271-8.

6. Im HJ, Kim TS, Park SY, et al. Prediction of tumour necrosis fractions using metabolic and volumetric 18F-FDG PET/CT indices, after one course and at the completion of neoadjuvant chemotherapy, in children and young adults with osteosarcoma. Eur J Nucl Med Mol Imaging. 2012;39:39-49.

7. Cistaro A, Lopci E, Gastaldo L, et al. The role of 18F-FDG PET/ CT in the metabolic characterization of lung nodules in pediatric patients with bone sarcoma. Pediatr Blood Cancer. 2012;59:1206-10.

8. Pevarski D, Drane W, Scarborough. The Usefulness of Bone Scintigraphy with SPECT Images for Detection of Pulmonary Metastases from Osteosarcoma. M. AJR 1998;170:319-22. 0361-803X/98/1702-319.

9. Рыжков АД, Иванов СМ, Ширяев СВ и др. ОФЭКТ/КТ в контроле лучевого лечения костных метастазов остеосаркомы. Вопросы онкологии, 2016;62(5):654-9.

10. Рыжков АД, Ширяев СВ, Мачак ГН, и др. ОФЭКТ/КТ в контроле лечения костных метастазов остеосаркомы методом ультразвуковой термоаблации. Медицинская радиология и радиационная безопасность. 2016;5:54-8.

11. Рыжков АД, Крылов АС, Мачак ГН, и др. Возможности остеосцинтиграфии и дополнительных радионуклидных методик в диагностике и лечении больных с остеогенной саркомой. Онкологический журнал. Лучевая диагностика, лучевая терапия. 2023;6(2):20-33. https://doi.org/10.37174/2587-7593-2023-6-2-20-33. https://doi.org/10.37174/2587-7593-2023-6-2-20-33. (In Russ.).

12. Рыжков АД, Крылов АС, Мачак ГН, и др. Мониторинг лечения метастазов остеосаркомы с помощью ОФЭКТ/КТ. Медицинская радиология и радиационная безопасность. 2019;64(4):76-88.

13. Петриев ВМ, Тищенко ВК, Красикова РН. 18F-ФДГ и другие меченые производные глюкозы для использования в радионуклидной диагностике онкологических заболеваний (обзор). Химико-фармацевтический журнал. 2016;50(4):3-14.

14. Allott L, Aboagye O. Chemistry Considerations for the Clinical Translation of Oncology PET Radiopharmaceuticals. Mol. Pharmaceutics 2020;17(7):2245-59. https://doi.org/10.1021/acs.molpharmaceut.0c00328.

15. Brenner W, Bohuslavizki KH, Eary JF. PET Imaging of Osteosarcoma J Nuclear Med. June 2003;44(6):930-42.

16. Lodge MA, Lucas JD, Marsden PK, et al. A PET study of 18FDG uptake in soft tissue masses. Eur J Nucl Med. 1999;26:22-30.

17. Ichiya Y, Kuwabara Y, Otsuka M, et al. Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography. J Nucl Med. 1991;32:1655-60.

18. Patlak CS, Blasberg RG. Graphical evaluation of blood-tobrain transfer constants from multiple-time uptake data: generalizations. J Cereb Blood Flow Metab. 1985;5:584-90.

19. Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab. 1983;3:1-7.

20. Gjedde A. Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: a re-examination. Brain Res. 1982;257:237-74.

21. Phelps ME, Huang SC, Hoffman EJ, et al. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol. 1979;6:371-88.

22. Kinahan PE, Fletcher JW. Positron emission tomography-computed tomography standardized uptake values in clinical practice and assessing response to therapy. Semin Ultrasound CT MR. 2010 Dec;31(6):496-505. https://doi.org/10.1053/j.sult.2010.10.001.

23. Liu, F, Zhang, Q, Zhou, D. et al. Effectiveness of 18F-FDG PET/CT in the diagnosis and staging of osteosarcoma: a meta-analysis of 26 studies. BMC Cancer 19, 323 (2019). https://doi.org/10.1186/s12885-019-5488-5.

24. Franzius C, Bielack S, Flege S, et al. Prognostic significance of 18F-FDG and 99mTc-methylene diphosphonate uptake in primary osteosarcoma. J Nucl Med. 2002;43:1012-7.

25. Hurley C, McCarville MB, Shulkin BL, et al. Comparison of 18F-FDG-PET-CT and Bone Scintigraphy for Evaluation of Osseous Metastases in Newly Diagnosed and Recurrent Osteosarcoma. Pediatr Blood Cancer. 2016 Aug;63(8):1381- 6. https://doi.org/10.1002/pbc.26014.

26. Page RL, Garg PK, Garg S, et al. PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody Fab fragment. J Nucl Med. 1994;35:1506-13.

27. Rasey JS, Koh WJ, Grierson JR, Grunbaum Z, Krohn KA. Radiolabelled fluoromisonidazole as an imaging agent for tumor hypoxia. Int J Radiat Oncol Biol Phys. 1989;17:985-91.

28. Haubner R, Wester HJ, Burkhart F, et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med. 2001;42:326-36.

29. Haubner R, Wester HJ, Weber WA, et al. Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res. 2001;61:1781-5.

30. Sordillo PP, Benua RS, Gelbard AS, et al. Imaging of human tumors and organs with N-13-labeled L-methionine. Am J Physiol Imaging. 1986;1:195-200.

31. Doubrovin M, Ponomarev V, Beresten T, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci USA. 2001;98:9300-5.

32. Franzius C, Bielack S, Flege S, et al. High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma. Nuklearmedizin. 01 Dec 2001;40(6):215-20.

33. Anderson P, Wiseman G, Dispenzieri A, et. al. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol. 2002 Jan 1;20(1):189-96. https://doi.org/10.1200/JCO.2002.20.1.189.

34. Loeb D, et al. Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer. 2009. 115(11):2514-22. https://doi.org/10.1002/cncr.24286.

35. Anderson PM, et al. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma. Clin Cancer Res. 2005. 11(19 Pt 1):6895-900.

36. Loeb DM, et al Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma. Cancer 2010.116(23):5470-8.

37. Subbiah V, Anderson P, Rohren E. Alpha emitter radium 223 in high-risk osteosarcoma: first clinical evidence of response and blood-brain barrier penetration. JAMA Oncol. 2015. 1(2):253-5. https://doi.org/10.1001/jamaoncol.2014.289.

38. Anderson PM, Subbiah Vk, Rohren E. Bone-Seeking Radiopharmaceuticals as Targeted Agents of Osteosarcoma: Samarium-153-EDTMP and Radium-223. Advances in Experimental Medicine and Biology Current Advances in Osteosarcoma. Adv Exp Med Biol. 2014;804:291-304. https://doi.org/10.1007/978-3-319-04843-7_16.

39. Subbiah V, Anderson P, Kalevi K, et al. Alpha Particle Radium 223 Dichloride in High-risk Osteosarcoma: A Phase I Dose Escalation Trial. Clin Cancer Res. 2019;25(13):3802-10. https://doi.org/10.1158/1078-0432.CCR-18-3964.

40. Baranowska-Kortylewicz J, Sharp J, McGuire T, et al. Alpha-Particle Therapy for Multifocal Osteosarcoma: A Hypothesis. Cancer Biother Radiopharm. 2020 Aug;35(6):418-24. https://doi.org/10.1089/cbr.2019.3112. Epub 2020 Feb 19.

41. Anderson P. Scott J. Parsai Sh., Zahler St. Worley S. Shrikanthan S. Subbiah V. Murphy E. 223-Radium for metastatic osteosarcoma: combination therapy with other agents and external beam radiotherapy. ESMO Open 2020;5(2):291-304. https://doi.org/10.1136/esmoopen-2019-000635.

42. Morgenstern A, et al. An Overview of Targeted Alpha Therapy with 225 Actinium and 213 Bismuth. Curr Radiopharm. 2018;11:200-8.

43. Reissig F, Zarschler K, Novy Z, et al. Towards Targeted Alpha Therapy with Actinium-225: Chelators for Mild Condition Radiolabeling and Targeting PSMA — A Proof of Concept Study. Cancers 2021;13(8):1974; https://doi.org/10.3390/cancers13081974.

44. Hagemann UB, et al. In Vitro and In Vivo Efficacy of a Novel CD33-Targeted Thorium-227 Conjugate for the Treatment of Acute Myeloid Leukemia. Mol Cancer Ther. 2016;15:2422- 31.

45. Gott M, Steinbach J, Mamat C. The radiochemical and radiopharmaceutical applications of radium. Open Chem. 2016;14:118-29.