medvisМедицинская визуализацияMedical Visualization1607-07632408-9516RDS-Media Ltd.medvis-51Research ArticleГОЛОВА И ШЕЯHEAD AND NECKПЭТ с18F-холином в диагностике глиальных опухолей головного мозгаUse18F-choline PET in Cerebral GliomasДолгушинМихаил БорисовичDolgushinMikhail Borisovichmdolgushin@mail.ruОджароваАкгуль АтаевнаOdzharovaAkgul Atayevnanoemail@neicon.ruТулинПавел ЕвгеньевичTulinPavel Yevgenyevichnoemail@neicon.ruВихроваНина БорисовнаVikhrovaNina Borisovnanoemail@neicon.ruНевзоровДенис ИльичNevzorovDenis Ilichnoemail@neicon.ruМеньковМихаил АлександровичMenkovMikhail Aleksandrovichnoemail@neicon.ruНечипайЭмилия АндреевнаNechipaiEmiliya Andreyevnanoemail@neicon.ruКобяковаЕкатерина АлексеевнаKobyakovaEkaterina Alekseyevnanoemail@neicon.ruБекяшевАли ХасьяновичBekyashevAli Khasyanovichnoemail@neicon.ruФГБУ “Российский онкологический научный центр им. Н.Н. Блохина”РоссияBlokhin Russian Cancer Research CenterRussian Federation201428062014037383Copyright © Долгушин М.Б., Оджарова А.А., Тулин П.Е., Вихрова Н.Б., Невзоров Д.И., Меньков М.А., Нечипай Э.А., Кобякова Е.А., Бекяшев А.Х., 20142014Долгушин М.Б., Оджарова А.А., Тулин П.Е., Вихрова Н.Б., Невзоров Д.И., Меньков М.А., Нечипай Э.А., Кобякова Е.А., Бекяшев А.Х.Dolgushin M.B., Odzharova A.A., Tulin P.Y., Vikhrova N.B., Nevzorov D.I., Menkov M.A., Nechipai E.A., Kobyakova E.A., Bekyashev A.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://medvis.vidar.ru/jour/article/view/51

Цель исследования: оценить диагностическую ценность позитронной эмиссионной томографии (ПЭТ) с18F-холином у больных с глиальными опухолями головного мозга. Материал и методы. В исследование включены результаты ПЭТ/КТ- и МРТ-исследований 28 пациентов с внутримозговыми опухолями: глиобластомы - у 8 (28,5%), анапластические астроцитомы - у 8 (28,5%), глиомы GrII - у 7 (25%), доброкачественные астроцитомы GrI - у 5 (18%). Всем пациентам была выполнена ПЭТ с18F-холином и минимум два МР-исследования в динамике. ПЭТ/КТ проводили на аппарате Biographm CT Siemens (КТ-300 мА, 120 кВ, КТ в спиральном режиме: шаг среза при реконструкции 1,2 мм, ПЭТ - на 4-рядном кольце детекторов на основе лютеция (48 блоков на каждый), ширина одной зоны сканирования (slab) 21,6 см, время сканирования на первом этапе 5 мин/slab, на втором - 10 мин/slab). Первый этап проводили сразу после внутривенного введения радиофармпрепарата (РФП) с помощью автоматического инжектора для РФП Intego 2010, второй - через 45-55 мин. Вводимая активность составляла 300 МБк. Количественную оценку SUV(max) проводили offline на рабочей станции SyngoVia с использованием протокола Oncology. Результаты. Самые высокие средние значения накопления РФП (maxSUV1) были получены в анапластических астроцитомах и глиобластомах - 5,07 и 4,89 соответственно, наибольший средний прирост значений maxSUV2 отмечался в глиобластомах - 15,46%, самые низкие значения maxSUV1 были в глиомах GrI-0,76. Выводы. ПЭТ с использованием различных РФП предоставляет уникальную информацию о функциональном состоянии опухолей по ряду биологических процессов.18F-холин (N,N-диметил-N-18F-фторметил-2-гидро-ксиэтиламмоний) - это мембранный маркер, который позволяет оценить активность формирования мембраны клетки. В непораженном веществе головного мозга18F- холин практически не накапливается. Методика двухэтапного ПЭТ-сканирования с18F-холином головного мозга у больных с внутримозговыми опухолями позволила предположить степень их злокачественности, которая зависит как от уровня накопления РФП на первом этапе, так и от степени увеличения этих значений на втором этапе. Таким образом “прирост” значений maxSUV может иметь прогностическое значение в диагностике опухолевой активности образований.

Aim. To evaluate the diagnostic value of PET with18F- choline in patients with glial brain tumors. Materials and Methods. The analysis was based on data generated from PET/CT and MRI examinations of 28 patients with intracerebral tumors: glioblastomas - 8 (28.5%) cases, anaplastic astrocytomas - 8 (28.5%) cases, glioma GrII - 7 (25%) cases, benign astrocytoma GrI - 5 (18%) cases. All patients with brain neoplasms underwent a selective brain18F-choline PET/CT and MRI follow up at minimum two time points: for at least 6 months. All two-stage PET/CT studies were performed with Biographm CT Siemens (multidetector (64) helical CT scanner, 120 kV, 300 mA, slice thickness 1.2 mm; PET acquisitions occurred at 4 bed positions ( 48 lutetium based units each), scan slab- 21.6 cm, at the first stage 5 min / slab, the second 10 min / slab). The first registration was performed immediately after intravenous injection of the radiopharmaceutical (RP) using an automatic RP-injector Intego 2010. Then patient were scanned again with the same protocol 45-55 min after injection. Administered activity was 300 MBq. Images visually and semiquantitatively assessment, with maximum standardized uptake value registration (maxSUV1 - on the first stage and maxSUV2 - on the second), was performed offline on a Syngo Via workstation using Oncology protocol. Results. The highest average maxSUV1 were observed in anaplastic astrocytomas and glioblastomas - 5.07 and 4.89, respectively, but the highest average growth (in %) of maxSUV2 observed in glioblastomas - 15.46%. The lowest maxSUV1 0.76 was registered in low-grade gliomas GrI. Conclusion. PET using different RP, provides unique information on the functional status of tumors for a variety of biological processes.18F-choline (N,N-dimethyl-N-18F-fluoromethyl-2-hydroxyethylammonium) is a marker of cell membrane lipid metabolism, so it could allow estimating the activity of cell membranes formation. An unaffected brain substance almost does not accumulate18F-choline. Two-stage PET technique of brain scanning with18F-choline enabled us to assume the gradate of malignancy of intracranial tumors - which depends on both the level of accumulation of RP in the first stage (maxSUV1) and the degree of uptake increase in the second stage (maxSUV2). Thus, the increment of maxSUV2 may be useful in the evaluation of tumor activity.

ПЭТглиомаголовной мозг18F-холинPET18F-cholinegliomabrainReferencesHaacke E.M., Mittal S., Wu Z. et al. Susceptibility-Weighted Imaging: Technical Aspectsand Clinical Applications. Am. J. Neuroradiol. 2009; 30: 19-30.Haacke E.M., Mittal S., Wu Z. et al. Susceptibility-Weighted Imaging: Technical Aspectsand Clinical Applications. Am. J. Neuroradiol. 2009; 30: 19-30.Пронин И.Н., Туркин А.М., Долгушин М.Б. и др. Тканевая контрастность, обусловленная магнитной восприимчивостью: применение в нейрорентгенологии. Мед. виз. 2011; 1: 8-12.Пронин И.Н., Туркин А.М., Долгушин М.Б. и др. Тканевая контрастность, обусловленная магнитной восприимчивостью: применение в нейрорентгенологии. Мед. виз. 2011; 1: 8-12.Schaefer P., Roccatagliata L., Ledezma C. et al. First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intraarterial therapy. Am. J. Neuroradiol. 2006; 27: 20-25.Schaefer P., Roccatagliata L., Ledezma C. et al. First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intraarterial therapy. Am. J. Neuroradiol. 2006; 27: 20-25.Долгушин М.Б., Пронин И.Н., Фадеева Л.М., Корниенко В.Н. Метод КТ-перфузии в дифференциальной диагностике вторичного опухолевого поражения головного мозга. Мед. виз. 2007; 4: 100-106.Долгушин М.Б., Пронин И.Н., Фадеева Л.М., Корниенко В.Н. Метод КТ-перфузии в дифференциальной диагностике вторичного опухолевого поражения головного мозга. Мед. виз. 2007; 4: 100-106.Пронин И.Н., Фадеева Л.М., Захарова Н.Е. и др. Перфузионная КТ: исследование мозговой гемодинамики в норме. Мед. виз. 2007; 3: 8-12.Пронин И.Н., Фадеева Л.М., Захарова Н.Е. и др. Перфузионная КТ: исследование мозговой гемодинамики в норме. Мед. виз. 2007; 3: 8-12.Долгушин М.Б., Пронин И.Н. Перфузионная компьютерная томография в динамической оценке эффективности лучевой терапии при вторичном опухолевом поражении головного мозга. Вестн. РОНЦ им. Н.Н. Блохина РАМН. 2008; 4: 36-46.Долгушин М.Б., Пронин И.Н. Перфузионная компьютерная томография в динамической оценке эффективности лучевой терапии при вторичном опухолевом поражении головного мозга. Вестн. РОНЦ им. Н.Н. Блохина РАМН. 2008; 4: 36-46.Burtscher I.M., Skagerberg G., Geijer B. et al. Proton MR spectroscopy and preoperative diagnostic accuracy: An evaluation of intracranial mass lesions characterized by stereotactic biopsy findings. Am. J. Neuroradiol. 2000; 21: 84-93.Burtscher I.M., Skagerberg G., Geijer B. et al. Proton MR spectroscopy and preoperative diagnostic accuracy: An evaluation of intracranial mass lesions characterized by stereotactic biopsy findings. Am. J. Neuroradiol. 2000; 21: 84-93.Подопригора А.Е., Пронин И.Н., Фадеева Л.М. Протонная магнитно-резонансная спектроскопия в диагностике опухолевых и неопухолевых поражений головного мозга. Вопр. нейрохир. 2000; 3: 7-20.Подопригора А.Е., Пронин И.Н., Фадеева Л.М. Протонная магнитно-резонансная спектроскопия в диагностике опухолевых и неопухолевых поражений головного мозга. Вопр. нейрохир. 2000; 3: 7-20.Ando K., Ishikura R., Nagami Y. et al. Usefulness of Cho/Cr ratio in proton MR spectroscopy for differentiating residual/recurrent glioma from non-neoplastic lesions. Nippon. Igaku Hoshasen Gakkai. 2004; 64: 121-126.Ando K., Ishikura R., Nagami Y. et al. Usefulness of Cho/Cr ratio in proton MR spectroscopy for differentiating residual/recurrent glioma from non-neoplastic lesions. Nippon. Igaku Hoshasen Gakkai. 2004; 64: 121-126.Hollingworth W., Medina L., Lenkinski R. et al. A systematic literature review of magnetic resonance spectroscopy (MRS) for the characterization of brain tumors. Am. J. Neuroradiol. 2006; 27; 7: 1404-1411.Hollingworth W., Medina L., Lenkinski R. et al. A systematic literature review of magnetic resonance spectroscopy (MRS) for the characterization of brain tumors. Am. J. Neuroradiol. 2006; 27; 7: 1404-1411.Hara T., Kosaka N., Shinoura N. et al. PET imaging of brain tumor with [methyl-11C] choline. J. Nucl. Med. 1997; 38: 842-847.Hara T., Kosaka N., Shinoura N. et al. PET imaging of brain tumor with [methyl-11C] choline. J. Nucl. Med. 1997; 38: 842-847.Shinoura, N., Nishijima M., Hara T. et al. Brain tumors: detection with C-11 choline PET. Radiology. 1997; 202; 2: 497-503.Shinoura, N., Nishijima M., Hara T. et al. Brain tumors: detection with C-11 choline PET. Radiology. 1997; 202; 2: 497-503.Langen K.J., Jarosch M., Muhlensiepen H. et al. Comparison of fluorotyrosinesand methionine uptake in F98 rat gliomas. Nucl. Med. Biol. 2003; 30: 501-508.Langen K.J., Jarosch M., Muhlensiepen H. et al. Comparison of fluorotyrosinesand methionine uptake in F98 rat gliomas. Nucl. Med. Biol. 2003; 30: 501-508.Kwee S.A., Ko J.P., Jiang C.S. et al. Solitary brain lesions enhancing at MR imaging: evaluation with fluorine 18 fluorocholine PET. Radiology. 2007; 244: 557-565.Kwee S.A., Ko J.P., Jiang C.S. et al. Solitary brain lesions enhancing at MR imaging: evaluation with fluorine 18 fluorocholine PET. Radiology. 2007; 244: 557-565.Wyss M.T., Spaeth N., Biollaz G. et al. Uptake of 18F-Fluorocholine, 18F-FET, and 18F-FDG in C6 gliomas and correlation with 131I-SIP(L19), a marker of angiogenesis. J. Nucl. Med. 2007; 48; 4: 608-614.Wyss M.T., Spaeth N., Biollaz G. et al. Uptake of 18F-Fluorocholine, 18F-FET, and 18F-FDG in C6 gliomas and correlation with 131I-SIP(L19), a marker of angiogenesis. J. Nucl. Med. 2007; 48; 4: 608-614.Wester H.J., Herz M., Weber W. et al. Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J. Nucl. Med. 1999; 40: 205-212.Wester H.J., Herz M., Weber W. et al. Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J. Nucl. Med. 1999; 40: 205-212.Gauthier S., Diksic M., Yamamoto L. et al. Positron emission tomography with [11C] choline in human subjects. Can. J. Neural. Sci. 1985; 12: 214.Gauthier S., Diksic M., Yamamoto L. et al. Positron emission tomography with [11C] choline in human subjects. Can. J. Neural. Sci. 1985; 12: 214.Amane S.P., Honig M.A., Milner T.A. et al. Sites of acetylcholine synthesis and release associated with microvessels in cerebral cortex: ultrastructural and neurochemical studies. J. Cereb. Blood Flow Metab. 1987; 7: 5330.Amane S.P., Honig M.A., Milner T.A. et al. Sites of acetylcholine synthesis and release associated with microvessels in cerebral cortex: ultrastructural and neurochemical studies. J. Cereb. Blood Flow Metab. 1987; 7: 5330.Hamel E., Assumel-Lurdin C., Edvinsson L. et al. Neuronal versusendothelial origin of vasoactive acethylcholine in pial vessels. Brain Res. 1987; 420: 391-396.Hamel E., Assumel-Lurdin C., Edvinsson L. et al. Neuronal versusendothelial origin of vasoactive acethylcholine in pial vessels. Brain Res. 1987; 420: 391-396.Estrada C., Bready J., Berliner J., Cancilla P.A. Choline uptake by cerebral capillaryendothelial cells in culture. J. Neurochem. 1990; 54: 1467-1473.Estrada C., Bready J., Berliner J., Cancilla P.A. Choline uptake by cerebral capillaryendothelial cells in culture. J. Neurochem. 1990; 54: 1467-1473.Haubrich D.R., Wang P.F.L., Wedeking P.W. Distribution and metabolism of intravenously administered choline[methyl-3H] and synthesis in vivo of acetylcholine in various tissues of guinea pigs. J. Pharmacol. Exp.Ther. 1975; 193: 246-255.Haubrich D.R., Wang P.F.L., Wedeking P.W. Distribution and metabolism of intravenously administered choline[methyl-3H] and synthesis in vivo of acetylcholine in various tissues of guinea pigs. J. Pharmacol. Exp.Ther. 1975; 193: 246-255.DeGrado T.R., Baldwin S.W., Wang S. et al. Synthesis and evaluation of(18)F-labeled choline analogs as oncologic PET tracers. J. Nucl. Med. 2001; 42: 1805-1814.DeGrado T.R., Baldwin S.W., Wang S. et al. Synthesis and evaluation of(18)F-labeled choline analogs as oncologic PET tracers. J. Nucl. Med. 2001; 42: 1805-1814.Moore K.R., Harnsberger H.R., Shelton C., Davidson H.C. “Leave me alone” lesions of the petrous apex. Am. J. Neuroradiol. 1998; 19: 733-738.Moore K.R., Harnsberger H.R., Shelton C., Davidson H.C. “Leave me alone” lesions of the petrous apex. Am. J. Neuroradiol. 1998; 19: 733-738.Katz-Brull R., Degani H. Kinetics of choline transport and phosphorylationin human breast cancer cells NMR application of the zero transmethod. Anticancer Res. 1996; 16: 1375-1380.Katz-Brull R., Degani H. Kinetics of choline transport and phosphorylationin human breast cancer cells NMR application of the zero transmethod. Anticancer Res. 1996; 16: 1375-1380.Nakagami K., Uchida T., Ohwada S. et al. Increased choline kinaseactivity and elevated phosphocholine levels in human colon cancer. Jpn. J. Cancer Res. 1999; 90: 419-424.Nakagami K., Uchida T., Ohwada S. et al. Increased choline kinaseactivity and elevated phosphocholine levels in human colon cancer. Jpn. J. Cancer Res. 1999; 90: 419-424.Ramirez de Molina A., Rodriguez-Gonzalez A., Gutierrez R. et al. Overexpression of choline kinase is a frequent feature in human tumorderivedcell lines and in lung, prostate, and colorectal human cancers. Biochem. Biophys. Res. Commun. 2002; 296: 580-583.Ramirez de Molina A., Rodriguez-Gonzalez A., Gutierrez R. et al. Overexpression of choline kinase is a frequent feature in human tumorderivedcell lines and in lung, prostate, and colorectal human cancers. Biochem. Biophys. Res. Commun. 2002; 296: 580-583.Slack B.E., Richardson U., Nitsch R.M., Wurtman R.J. Dioctanoylglycerol stimulates accumulation of [methyl-'4C]choline and its incorporation into acetylcholine and phosphatidylcholine in a human cholinergic neuroblastoma cell line. Brain Res. 1972; 585: 169-176.Slack B.E., Richardson U., Nitsch R.M., Wurtman R.J. Dioctanoylglycerol stimulates accumulation of [methyl-'4C]choline and its incorporation into acetylcholine and phosphatidylcholine in a human cholinergic neuroblastoma cell line. Brain Res. 1972; 585: 169-176.Yavin I. Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture: patterns of acetylcholine, phosphocholine and cholinephosphoglycerides labeling from [C] cholin. J. Biol. 1976; 251: 1392-1397.Yavin I. Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture: patterns of acetylcholine, phosphocholine and cholinephosphoglycerides labeling from [C] cholin. J. Biol. 1976; 251: 1392-1397.Galea E., Estrada C. Ouabaine-sensitive choline transport system in capillaries isolated from bovine brain. J. Neurochem. 1992; 59: 936-941.Galea E., Estrada C. Ouabaine-sensitive choline transport system in capillaries isolated from bovine brain. J. Neurochem. 1992; 59: 936-941.Vanpouille C., Le Jeune N., Kryza D. et al. Influence of multidrug resistance on (18)F-FCH cellular uptake in a glioblastoma model. Eur. J. Nucl. Med. Mol. Imaging. 2009; 36 (8): 1256-1264.Vanpouille C., Le Jeune N., Kryza D. et al. Influence of multidrug resistance on (18)F-FCH cellular uptake in a glioblastoma model. Eur. J. Nucl. Med. Mol. Imaging. 2009; 36 (8): 1256-1264.Hara T., Kosaka N., Kishi H. PET imaging of prostate cancer using carbon-11-choline. J. Nucl. Med. 1998; 39: 990-995.Hara T., Kosaka N., Kishi H. PET imaging of prostate cancer using carbon-11-choline. J. Nucl. Med. 1998; 39: 990-995.DeGrado T.R., Coleman R.E., Wang S. et al. Synthesis and evaluation of18F-labeled choline as an oncologic tracer for positron emission tomography: Initial findings in prostate cancer. Cancer Res. 2001; 61: 110-117.DeGrado T.R., Coleman R.E., Wang S. et al. Synthesis and evaluation of18F-labeled choline as an oncologic tracer for positron emission tomography: Initial findings in prostate cancer. Cancer Res. 2001; 61: 110-117.Hara T., Kosaka N., Kishi H. Development of (18)F-fluoroethylcholine for cancer imaging with PET: Synthesis, biochemistry, and prostatecancer imaging. J. Nucl. Med. 2002; 43: 187-199.Hara T., Kosaka N., Kishi H. Development of (18)F-fluoroethylcholine for cancer imaging with PET: Synthesis, biochemistry, and prostatecancer imaging. J. Nucl. Med. 2002; 43: 187-199.Ohtani T., Kurihara H., Ishiuchi S. et al. Brain tumour imaging with carbon-11-choline: Comparison with FDG PET and gadolinium-enhanced MR imaging. Eur. J. Nucl. Med. 2001; 28: 1664-1670.Ohtani T., Kurihara H., Ishiuchi S. et al. Brain tumour imaging with carbon-11-choline: Comparison with FDG PET and gadolinium-enhanced MR imaging. Eur. J. Nucl. Med. 2001; 28: 1664-1670.Provenzale J.M., McGraw P, Mhatre P et al. Peritumoral brain regions in gliomas and meningiomas: investigation with isotropic diffusion weighted MR imaging and diffusion-tensor MR imaging. Radiology. 2004; 232: 451-460.Provenzale J.M., McGraw P, Mhatre P et al. Peritumoral brain regions in gliomas and meningiomas: investigation with isotropic diffusion weighted MR imaging and diffusion-tensor MR imaging. Radiology. 2004; 232: 451-460.Goebell E., Paustenbach S., Vaeterlein O. et al. Low-grade and anaplastic gliomas: Differences in architecture evaluated with diffusion-tensor MR imaging. Radiology. 2006; 239: 217-222.Goebell E., Paustenbach S., Vaeterlein O. et al. Low-grade and anaplastic gliomas: Differences in architecture evaluated with diffusion-tensor MR imaging. Radiology. 2006; 239: 217-222.Tan H., Chen L., Guan Y., Lin X. Comparison of MRI, F-18 FDG, and 11C-choline PET/CT for their potentials in differentiating brain tumor recurrence from brain tumor necrosis following radiotherapy. Clin. Nucl. Med. 2011; 36 (11): 978-981.Tan H., Chen L., Guan Y., Lin X. Comparison of MRI, F-18 FDG, and 11C-choline PET/CT for their potentials in differentiating brain tumor recurrence from brain tumor necrosis following radiotherapy. Clin. Nucl. Med. 2011; 36 (11): 978-981.

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