VIZUALIZACIJA NEUROENDOKRINIH TUMORA METODAMA NUKLEARNE    MEDICINE

Jelena petrović; Djuro  Macut; Dragana Šobić Šaranović

doi:10.5937/mp71-27009

Jelena petrović Centar za nuklearnu mediicnu Kliničkog centra Srbije
Djuro Macut Klinika za endokrinologiju, dijabetes i bolesti metabolizma KCS, Medicinski fakultet u Beogradu
Dragana Šobić Šaranović Centar za nuklearnu mediicnu KCS, Medicinski fakultet u Beogradu

DOI: https://doi.org/10.5937/mp71-27009

Ključne reči: neuroendokrini tumori, pozitronska emisiona tomografija, gama kamera, radiofarmaci

Sažetak

Neuroendokrini tumori (NET) su relativno retki i heterogeni sa vrlo heterogenom kliničkom slikom. Potiču iz senzornih i sekretornih neuroendokrinih ćelija uglavnom unutar plućnog i gastrointestinalnog trakta. Sačinjavaju manje od 2% svih malignih oboljenja. Na osnovu kliničkog ponašanja, histologije i proliferacije, podeljeni su u dobro diferentovane (niski do srednji stepen) i slabo diferentovane (visoki stepen) neuroendokrine tumore. Pripadnost svakoj od ovih kategorija ima uticaj na lečenje i prognozu. Jedino lečenje je operacija. S obzirom da više od 50% pacijenata u vreme postavljanja dijagnoze već ima metastatsku bolest, mora biti uključeno sistemsko lečenje, kao što su hemoterapija i “target” terapija, kao i radioterapija peptidnim receptorima. Za dijagnozu i praćenje ovih tumora koriste se različite radiološke metode (kompjuterizovana tomografija, magnetna rezonanca, ultrazvuk) kao i endoskopija. Metode nuklearne medicine koriste njihove jedinstvene osobine, uglavnom karakteristike prekursora amina i sistema dekarboksilacije, kao i ekspresije receptora somatostatina. Radionuklidne metode vizualizuju celo telo i mogu lokalizovati i udaljene metastaze. Snimanje se može obaviti pomoću gama kamere (SPECT, SPECT / CT) ili pozitronskom-emisionom tomografijom (PET / CT). Radiofarmaci koji se koriste za snimanje gama kamerom obično su ^99mTc- (V) -DMSA, ^99mTc-MIBI, ^99mTc-HYNIC TOC, ¹¹¹In-pentetreotid i ¹³¹I-MIBG / ¹²³I-MIBG. PET/CT snimanje ima prednost superiorne prostorne rezolucije i brzine snimanja. Najčešće korišćeni pozitronski radiofarmaci su analozi ⁶⁸Ga-DOTA-somatostatina, ¹⁸FDG (naročito za tumore visokog stepena), ¹⁸F-L-DOPA / ¹¹C-L-DOPA i ¹¹C-5-hidroksitriptofan. Dalji razvoj novih radiofarmaka za detekciju neuroendokrinih tumora predstavlja veliki izazov. U ovom radu je dat revijski prikaz najčešće korišćenih tehnologija kao i trendovi razvoja metoda za otkrivanje neuroendokrinih tumora.

Reference

References
1. Koopmans KP, Neels ON, Kema IP, Elsinga PH, Links TP, de Vries EG, Jager PL. Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results. Crit Rev Oncol Hematol 2009; 71:199-213.
2. Maecke HR, Reubi JC. Somatostatin receptors as targets for nuclear medicine imaging and radionuclide treatment. J Nucl Med 2011; 52:841–844.
3. Sobic-Saranovic DP, Pavlovic SV, Artiko VM, Saranovic DZ, Jaksic ED, Subotic D, Nagorni-Obradovic L, Kozarevic N, Petrovic N, Grozdic IT, Obradovic VB. The utility of two somatostatin analog radiopharmaceuticals in assessment of radiologically indeterminate pulmonary lesions. Clin Nucl Med 2012; 37:14-20.
4. Ginj M, Zhang H, Waser B, Cescato R, Wild D, Wang X, Erchegyi J, Rivier J, Mäcke HR, Reubi JC. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci USA 2006; 103:16436-41.
5. Dalm SU, Nonnekens J, Doeswijk GN, de Blois E, van Gent DC, Konijnenberg MW, de Jong M. Comparison of the Therapeutic Response to Treatment with a 177Lu-Labeled Somatostatin Receptor Agonist and Antagonist in Preclinical Models. J Nucl Med 2016; 57:260-5.
6. Wild D, Fani M, Behe M, Brink I, Rivier JE, Reubi JC, Maecke HR, Weber WA. First clinical evidence that imaging with somatostatin receptor antagonists is feasible. J Nucl Med 2011; 52:1412-7.
7. Artiko V, Sobic-Saranovic D, Pavlovic S, Petrovic M, Zuvela M, Antic A, Matic S, Odalovic S, Petrovic N, Milovanovic A, Obradovic V. The clinical value of scintigraphy of neuroendocrine tumors using (99m)Tc-HYNIC-TOC. J BUON 2012; 17:537-42.
8. Raderer M, Kurtaran A, Leimer M, Angelberger P, Niederle B, Vierhapper H, Vorbeck F, Hejna MH, Scheithauer W, Pidlich J, Virgolini I. Value of peptide receptor scintigraphy using (123)I-vasoactive intestinal peptide and (111)In-DTPA-D-Phe1-octreotide in 194 carcinoid patients: Vienna University Experience, 1993 to 1998. J Clin Oncol 2000; 18:1331-6.
9. Anzola-Fuentes LK, Chianelli M, Galli F, Glaudemans AW, Martin Martin L, Todino V, Migliore A, Signore A. Somatostatin receptor scintigraphy in patients with rheumatoid arthritis and secondary Sjögren's syndrome treated with Infliximab: a pilot study. EJNMMI Res 2016; 6(1):49.
10. Naswa N, Sharma P, Kumar A, et al. Gallium-68-DOTA-NOC PET/CT of Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Single-Center Study. AJR 2011; 197:1221–1228.
11. Johnbeck CB, Knigge U, Kjaer A. Somatostatin receptor imaging with PET tracers of neuroendocrine tumors: current status and review of the literature. Future Oncol 2014; 10:2259–77.
12. Koukouraki S, Strauss LG, Georgoulias V, Eisenhut M, Haberkorn U, Dimitrakopoulou-Strauss A. Comparison of the pharmacokinetics of Ga-68-DOTATOC and [F-18]FDG in patients with metastatic neuroendocrine tumours scheduled for Y-90-DOTATOC therapy. Eur J Nucl Med Mol Imag 2006; 33:1115–22.
13. Kayani I, Bomanji JB, Groves A, et al. Functional Imaging of neuroendocrine tumors with combined PET/CT using Ga-68-DOTATATE (Dota-DPhe(1),Tyr(3)-octreotate) and F-18-FDG. Cancer 2008;112:2447–55.
14. Gabriel M, Decristoforo C, Kendler D, et al. Ga-68-DOTA-Tyr(3)-octreotide PET in euroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007; 48:508–18.
15. Shapiro B, Gross MD, Shulkin B. Radioisotope diagnosis and therapy of malignant pheochromocytoma. Trends Endocrinol Metab 2001; 12:469–475.
16. Binderup T, Knigge U, Loft A, Mortensen J, Pfeifer A, Federspiel B, et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med Soc Nuc Med 2010; 51:704–12.
17. Denoyer D, Perek N, Le Jeune N, Frere D, Dubois F. Evidence that 99mTc-(V)-DMSA uptake is mediated by NaPi cotransporter type III in tumour cell lines. Eur J Nucl Med Mol Imaging 2004; 31:77-84.
18. Clarke SE, Lazarus CR, Wraight P, Sampson C, Maisey MN. Pentavalent [99mTc]DMSA, [131I]MIBG, and [99mTc]MDP--an evaluation of three imaging techniques in patients with medullary carcinoma of the thyroid. J Nucl Med 1988; 29:33-8.
19. Adams S, Acker P, Lorenz M, Staib-Sebler E, Hor G. Radioisotope-guided surgery in patients with pheochromocytoma and recurrent medullary thyroid carcinoma—a comparison of preoperative and intraoperative tumor localization with histopathologic findings. Cancer 2001; 92:263–70.
20. de Groot JWB, Links TP, Jager PL, Kahraman T, Plukker JTM. Impact of F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in patients with biochemical evidence of recurrent or residual medullary thyroid cancer. Ann Surg Oncol 2004; 11:786–94.
21. Diehl M, Risse JH, Brandt-Mainz K, et al. Fluorine-18fluorodeoxyglucose positron emission tomography in medullary thyroid cancer: results of a multicentre study. Eur J Nucl Med 2001; 28:1671–6.
22. Carrasquillo JA, Chen CC. Molecular imaging of neuroendocrine tumors. Semin Oncol 2010; 37:662-79.
23. Beheshti M, Pocher S, Vali R, et al. The value of F-18-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with F-18-FDG PET-CT. Eur Radiol 2009; 19:1425–34.
24. Conry BG, Papathanasiou ND, Prakash V, et al. Comparison of Ga-68-DOTATATE and F-18-fluorodeoxyglucose PET/CT in the detection of recurrent medullary thyroid carcinoma. Eur J Nucl Med Mol Imag 2010; 37:49–57.
25. Taieb D, Tessonnier L, Sebag F, et al. The role of F-18-FDOPA and F-18-FDG-PET in the management of malignant and multifocal phaeochromocytomas. Clin Endocrinol 2008; 69:580–6.
26. Timmers H, Chen CC, Carrasquillo JA, et al. Comparison of F-18-fluoro-L-DOPA, F-18-fluoro-deoxyglucose, and F-18-fluorodopamine PET and I-123-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. Clin Endocrinol Metab 2009; 94:4757–67.
27. Wouter W de Herder. GEP-NETs update: Functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs). Eur J Endocrinology 2014; 170: 173–183
28. Fani M, Peitl PK, Velikyan I. Current Status of Radiopharmaceuticals for the Theranostics of Neuroendocrine Neoplasms. Pharmaceuticals (Basel) 2017; 10(1):30.
29. Hörsch D, Kulkarni HR, Baum RP. THERANOSTICS—clinical aimshots in surgical warfare against well-differentiated neuroendocrine neoplasms. Ann Transl Med 2014;2(1):1.
30. Adams S, Baum RP, Hertel A, Schumm-Draeger PM, Usadel KH, Hör G. Intraoperative gamma probe detection of neuroendocrine tumors. J Nucl Med 1998; 39:1155–60.