Conclusiones

La introducción de nuevos agentes radiofarmacéuticos basados en pequeños péptidos marcados constituyen una importante alternativa en el tratamiento de tumores neuroendocrinos. Debido a sus atractivas propiedades farmacocinéticas y elevada afinidad por el receptor específico sobre-expresado en tumor. No obstante, aún quedan por resolver problemas relacionados con la distribución heterogénea del radiopéptido sobre la lesión, principalmente en tumores sólidos de gran tamaño inoperables. Nuevos agentes radioterapéuticos más efectivos continúan en estudio. El futuro uso clínico de los mismos posibilitará reducir aún más el tamaño tumoral, controlar los síntomas, y por ende, contribuirá con el mejoramiento de la calidad de vida y prolongación de la sobrevida de los pacientes oncológicos.

Referencias bibliográficas

1.     Ronald E. Weiner and Mathew L. Thakur. Radiolabeled Peptides in Oncology Role in Diagnosis and Treatment. Biodrugs 2005; 19 (3): 145 - 63.

2.     Kaltsas G, Mukherjee JJ, Plowman PN et al. The role of chemotherapy in the nonsurgical management of malignant neuroendocrine tumours. Clinical Endocrinology 2001; 55: 575–87.

3.     Oates JA: The carcinoid syndrome. N Engl J Med 1986; 315:702-4.

4.     Quintana J C. Terapia de Tumores Neuroendocrinos: Generalidades. Medwave. Edición Mayo 2005. Año 5, No. 4.

5.     Benevento A, Boni L, Frediani L et al. Result of liver resection as treatment for metastases from noncolorectal cancer. J Surg Oncol 2000, 74:24-9.

6.     Bombardieri et al. Position of nuclear medicine techniques in the diagnostic work-up of neuroendocrine tumors. Q J Nucl Med Mol Imaging 2004; 48:150-63.

7.     Oberg K, Astrup L, Eriksson B et al. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms).I. General overview. Acta Oncology 2004 ;43: 617–25.

8.     Kaltsas GA, Besser GM & Grossman AB The diagnosis and medical management of advanced neuroendocrine tumors. Endocrine Reviews 2004; 25 : 458–511.

9.     Oberg K: Endocrine tumors of the gastrointestinal tract: systemic treatment. Anticancer Drugs 1994, 5:503-19.

10.   Veenendaal LM, Borel Rinkes IHM, Cornelis JM Lips et al. Review Liver metastases of neuroendocrine tumours; early reduction of tumour load to improve life expectancy. World Journal of Surgical Oncology 2006, 4:35.

11.   Liu LX, Zhang WH, Jiang HC: Current treatment for liver metastases from colorectal cancer. World J Gastroenterol 2003, 9:193-200.

12.   Roche A: [Hepatic chemo-embolization]. Bull Cancer 1989, 76:1029-37.

13.   Florman S, Toure B, Kim L et al: Liver transplantation for neuroendocrine tumors. J Gastrointest Surg 2004, 8:208-12.

14.   Wettstein M, Vogt C, Cohnen M et al: Serotonin release during percutaneous radiofrequency ablation in a patient with symptomatic liver metastases of a neuroendocrine tumor. Hepatogastroenterology 2004, 51:830-2.

15.   Anna M Wu, Peter D Senter. Arming antibodies: prospects and challenges for inmunoconjugates. Nature Biotechnology 2005; 23 (9); 1137-46.

16.   Jain RK. Tumor physiology and antobody delivery. Front. Radiat. Ther. Oncol2, 1990. 32-46; 64-8.

17.   Ruiz-Cabello F, Cabrera T, López-Nevot MA & Garrido F. Impaired surface antigen presentation in tumors: implications for T cell-based immunotherapy. Semin Cancer Bio 2002. 12:15-24.

18.   Krenning EP, de Jong M, Kooij PP et al. Radiolabelled somatostatin analogue (s) for peptide receptor scintigraphy and radionuclide therapy. Annals of Oncology 1999; 10 (Suppl 2) S23–S29.

19.   Kwekkeboom DJ, Krenning EP, de Jong M. Peptide receptor imaging and therapy. J Nucl Med. 2000;41:1704 –13.

20.   Merlo A, Hausmann O, Wasner M, et al. Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0- D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas. Clin Cancer Res. 1999; 5:1025–33.

21.   Wiseman GA & Kvols LK. Therapy of neuroendocrine tumors with radiolabeled MIBG and somatostatin analogues. Seminars in Nuclear Medicine 1995; 25 272–8.

22.   de Herder WW, Hofland LJ, van der Lely AJ et al. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocrine-Related Cancer 2003; 10: 451–8.

23.   Guillemin R. Peptide in the brain: The new endocrinology of the neurons. Science 1978; 202 : 390- 402.

24.   Amin I. Kassis & S. James Adelstein. Radiobiologic Principles in Radionuclide Therapy. Journal Of Nuclear Medicine 2005; 46 :1 (Suppl) .

25.   Stepanek J, Larsson B, Weinreich R. Auger-electron spectra of radionuclides for therapy and diagnostics. Acta Oncology 1996; 35 : 863 - 8.

26.   Pauwels S, Barone R, Walrand S et al. Practical dosimetry of peptide receptor radionuclide therapy with 90Y-labeled somatostatin analogs. J Nucl Med 2005; 46 (Suppl 1) 92S - 98S.

27.   Bodei L, Cremonesi M, Grana C et al. Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. European Journal of Nuclear Medicine and Molecular Imaging 2004; 31: 1038–46.

28.   Kaltsas GA, Papadogias D, Makras P et al. Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues Endocrine-Related Cancer 2005; 12: 683 - 99.

29.   Krenning EP, Bakker WH, Breeman WA. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet 1989; 4: 242-4.

30.   de Jong M, Valkema R, Jamar F et al. Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. Sem Nucl Med 2002; 32:133 - 40.

31.   McMurry TJ, Brechbiel M, Kumar K et al. Convenient Synthesis of Bifunctional Tetraaza Macrocycles. Bioconjugate Chem 1992; 3:108 -17.

32.   Reubi JC, Korner M, Waser B et al. High expression of peptide receptors as a novel target in gastrointestinal stromal tumours. European Journal of Nuclear Medicine and Molecular Imaging 2004; 31: 803–10.

33.   Reubi JC, Macke HR & Krenning EP Candidates for peptide receptor radiotherapy today and in the future. Journal of Nuclear Medicine 2005; 46 (Suppl 1): 67S–75S.

34.   Virgolini I, Britton K, Buscombe J et al. a In- and Y-DOTA-lanreotide: results and implications of the MAURITIUS trial. Seminars in Nuclear Medicine 2002; 32: 148–55.

35.   Virgolini I, Traub T, Novotny C et al. Experience with indium-111 and yttrium-90-labeled somatostatin analogs. Current Pharmacy Design 2002; 8: 1781–807.

36.   de Jong M, Breeman WA, Valkema R, Bernard BF & Krenning EP Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs. Journal of Nuclear Medicine 2005; 46 (Suppl 1): 13S–17S.

37.   Krenning EP, Kwekkeboom DJ, Valkema R et al. Peptide receptor radionuclide therapy. Annals of the New York Academy of Sciences 2004; 1014: 234–45.

38.   O’Donoghue JA, Bardies M, Wheldon TE. Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med 1995; 36:1902–9.

39.   Valkema R, Pauwels SA, Kvols LK et al. Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0),Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate. Journal of Nuclear Medicine 2005; 46 (Suppl 1): 83S–91S.

40.   Lewington VJ. Targeted radionuclide therapy for neuroendocrine tumours. Endocrine-Related Cancer 2003;10 : 497–501.

41.   Chinol M, Bodei L, Cremonesi M & Paganelli G Receptor-mediated radiotherapy with Y-DOTA-DPhe-Tyr-octreotide: the experience of the European Institute of Oncology Group. Seminars in Nuclear Medicine 2002; 32: 141–7.

42.   Waldherr C, Pless M, Maecke HR et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4GBq (90)Y-DOTATOC. Journal of Nuclear Medicine 2002; 43: 610–6.

43.   Krenning EP, Valkema R, Kwekkeboom DJ et al. Molecular imaging as in vivo molecular pathology for gastroenteropancreatic neuroendocrine tumors: implications for follow-up after therapy. Journal of Nuclear Medicine 2005; 46 (Suppl 1): 76S - 82S.

44.   Kwekkeboom DJ, Mueller-Brand J, Paganelli G et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. Journal of Nuclear Medicine 2005; 46 (Suppl 1) 62S–66S.

45.   Kwekkeboom DJ, Bakker WH, Teunissen JJM et al. Treatment with Lu-177-DOTA-Tyr3-octreotate in patients with neuroendocrine tumors: interim results [abstract]. Eur J Nucl Med Mol Imaging 2003; 30(suppl 2) : S231.

46.   Lam MG, Lips CJ, Jager PL et al: Repeated [131I]metaiodobenzylguanidine therapy in two patients with malignant pheochromocytoma. J Clin Endocrinol Metab 2005, 90:5888-95.

47.   Larson SM & Krenning EP A pragmatic perspective on molecular targeted radionuclide therapy. Journal of Nuclear Medicine 2005; 46 (Suppl 1): 1S–3S.

48.   Kaltsas GA, Besser M & Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocrine Reviews 2004; 25: 458–511.

49.   Varner JA. The role of vascular cell integrins alpha v beta 3 and alpha v beta 5 in angiogenesis. EXS. 1997;79: 361–90.

50.   Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD andintegrins. Science. 1987;238:491–7.

51.   Astrid Capello, Eric P. Krenning, Bert F. Bernard et al. Anticancer Activity of Targeted Proapoptotic Peptides J Nucl Med 2006; 47:122–9.

52.   Chen Y, Xu X, Hong S, et al.RGD-Tachyplesin inhibits tumor growth.Cancer Res 2001;61:2434–38.

53.   Anuradha CD, Kanno S, Hirano S. RGD peptide-induced apoptosis in human leukemia HL-60 cells requires caspase-3 activation. Cell Biol Toxicol. 2000;16:275–83.

54.   Chatterjee S, Brite KH, Matsumura A. Induction of apoptosis of integrinexpressing human prostate cancer cells by cyclic Arg-Gly-Asp peptides. Clin Cancer Res. 2001;7:3006–11.

55.   Bernard B, Capello A, van Hagen M, et al. Radiolabeled RGD-DTPA-Tyr3- octreotate for receptor-targeted radionuclide therapy. Cancer Biother Radiopharm. 2004;19:173–80.

56.   Nagy A, Schally AV, Halmos G, et al. Synthesis and biological evaluation of cytotoxic analogs of somatostatin containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin, Proc Natl Acad Sci USA. 1998;95:1794–99.