Imagen molecular del microentorno del cáncer

Alberto Signore, Filippo Galli, Sveva Auletta

Resumen

En las últimas décadas los investigadores han centrado su atención en la observación de las células cancerosas, en búsqueda de nuevos sitios blanco. Sin embargo, el crecimiento del tumor se produce en un entorno que, o inhibe, o contribuye a la expansión del tumor y su metástasis. Varios esfuerzos han estado enfocados al estudio del microentorno del cáncer, con propósitos diagnósticos o terapéuticos. La Medicina Nuclear puede contribuir a la comprensión de la complejidad y del papel que juega el microentorno del tumor, mediante la obtención de las imágenes de varios de sus componentes (receptores de quimioquinas, células inmunes, antígenos del estroma, factores vasculares, etc.). En un tumor, cada componente del microentorno ofrece muchos blancos potenciales para varias drogas o radiofármacos. El cáncer puede ser estudiado mediante diferentes estrategias y enfoques: mediante la imagen de marcadores tumorales, o la diferenciación de estos, con propósitos diagnósticos a fin de planificar terapias personalizadas (receptores agonistas o superagonistas); mediante la imagen del estroma del tumor y la vascularización, para monitorear la adhesión celular, la metástasis, la angiogénesis y la hipoxia; mediante la imagen de la respuesta del huésped de las células cancerosas, con el objetivo de monitorear la eficacia de las estrategias inmunoterapéuticas.

Palabras clave

linfocitos, imágenes, moléculas, linfocinas, metástasis, diagnóstico, terapia, endotelio, crecimiento

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Referencias

JOYCE JA & POLLARD JW. Micro environmental regulation of metastasis. Nature Reviews Cancer. 2009; 9(4): 239-252.

BALKWILL F & MANTOVANI A. Inflammation and cancer: back to Virchow? Lancet. 2001; 357(9255): 539-545.

GOUBRAN HA, KOTB RR, STAKIW J, et. al. Regulation of tumour growth and metastasis: the role of tumour microenvironment. Cancer Growth and Metastasis. 2014; 7: 9-18.

MANTOVANI A, ALLAVENA P, SICA A, BALKWILL F. Cancer related-related inflammation. Natue. 2008; 454(7203): 436-444.

ERLER JT, BENNEWITH KL, COX TR, et. al. Hypoxia-induced lysyl oxidise is a critical mediator of bone marrow cell recruitment to form the pre-metastatic niche. Cancer Cell. 2009; 15 (1): 35-44.

ZENG J, XIE K, WU H, et. al. Identification and functional study of cytokines and chemokines involved in tumourgenesis. Combinatorial Chemistry and High Throughput Screening. 2012; 15(3): 276-85.

FOLKMAN J. Role of angiogenesis in tumour growth and metastasis. Semin Oncol. 2002; 29 (6 Suppl 16): 15-8.

MAERTENS L, ERPICUM C, DETRY B, et. al. Bone marrow-derived mesenchymal stem cells drive lymph angiogenesis. PloS One. 2014; 9(9): e106976.

OLSSON AK, DIMBERG A, KREUGER J, CLAESSON-WELSH L. VEGF receptor signalling- in control of vascular function. Nat Rev. Mol Cell Biol. 2006; 7(5): 359-371.

MARU Y, YAMAGUCHI S, SHIBUYA M. Flt-1, a receptor for vascular endothelial growth factor, has trasforming and morphogenic potentials. Oncogene. 1998; 16(20): 2585-95.

GOEL HL, MERCURIO AM. VEGF targets the tumour cell. Nat Rev Cancer. 2013; 13(12): 871-82.

HOOD JD, CHERESH DA. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002; 2(2): 91-100.

BAUME DM, ROBERTSON MJ, LEVINE H, et. al. Differential responses to interleukin 2 defines functionally distinct subsets of human natural killer cells. Eur J Immunol. 1992; 22(1): 1-6.

PATEL KN, SHAHA AR. Poorly differentiated and anaplastic thyroid cancer. Cancer Control. 2006; 13(2): 119-28.

CREACH KM, NUSSENBAUM B, SIEGEL BA, GRIGSBY PW. Thyroid carcinoma uptake of 18F- fluoodeoxyglucose inpatients with elevated serum thyroglobulin and negative 131I scintigraphy. Am J Otolaryngol. 2013 Jan-Feb; 34(1): 51-6.

MIDDENDORP M, SELKINSKI I, HAPPEL C, et. al. Comparison of positron emission tomography with [(18)F]FDG and [(68)Ga]DOTATOC in recurrent differentiated thyroid cancer: preliminary data. Q J Nucl Med Mol Imaging. 2010; 54(1): 76-83.

PALMEDO H, BUCERIUS J, JOE A, et. al. Integrated PET/CT in differentiated thyroid cancer: diagnostic accuracy and impact on patient management. J. Nucl Med. 2006; 47(4): 616-624.

SHAMMAS A, DEGIRMENCY B, MOUNTZ JM, et. al. 18F-FDG PET/CT in patients with suspected recurrent or metastatic well-differentiated thyroid cancer. J. Nucl Med. 2007; 48(2): 221-226.

LAURI C, DI TRAGLIA S, GALLI F, PIZZICHINI P, SIGNORE A. Current status of PET imaging of differentiated thyroid cancer with second generation radiopharmaceuticals. Q J Nucl Med Mol Ima-ging. 2015; 59(1): 105-15.

DURANTE C, PUXEDDU E, FERRETTI E, et. al. BRAF mutations in papillary thyroid carcinoma inhibit genes involved in iodine metabolism. J Clin Endocrinol Metab. 2007; 92(7): 2840-3.

CORSETTI F, CHIANELLI M, CORNELISSEN B, et. al. Radioiodinated recombinant human TSH: a novel radiopharmaceutical for thyroid cancer metastases detection. Cancer Biother Radiopharm. 2004; 19(1): 57-63.

SZKUDLINSKI MW, GROSSMANN M, LEITOLF H, WEINTRAUB BD. Human thyroid-stimulating hormone: structure-function analysis. Methods. 2000; 21(1): 67-81.

GALLI F, MANNI I, PIAGGIO G, et. al. (99m)Tc-labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer. Thyroid. 2014; 24(8): 1297-308.

PHAN HT, JAGER PL, PLUKKER JT, et. al. Comparison of 11C-methionine PET and 18F-fluoodeoxyglucose PET in differentiated thyroid cancer. Nucl Med Commun. 2008; 29(8): 711-6.

PERRI F, PEZZULLO L, CHIOFALO MG, et. al. Targeted therapy: a new hope for thyroid carcinomas. Crit Rev Oncol Hematol. 2014; 94(1): 55-63.

DIJKGRAAF I, BOERMAN OC. Molecular imaging of angiogenesis with SPECT. Eur J Nucl Med Mol Imaging. 2010; 37(Suppl 1): S104-13.

YOSHIMOTO M, KINUYA S, KAWASHIMA A, et. al. Radioiodinated VEGF to image tumour angiogenesis in a LS180 tumour xenograft model. Nucl Med Biol. 2006; 33(8): 963-969.

LI S, PECK-RADOSAVLJEVIC M, KIENAST O, et. al. Imaging gastrointestinal tumours using vascular endothelial growth factor-165 (VEGF165) receptor scintigraphy. .Ann Oncol. 2003; 14(8): 1274-7.

BLANKENBERG FG, BACKER MV, LEVASHOVA Z, et. al. In vivo tumour angiogenesis imaging with site-specific labeled (99m)Tc-HYNIC-VEGF. Eur J Nucl Med Mol Imaging. 2006; 33(7): 841-8.

CHAN C, SANDHU J, GUHA A, et. al. A human transferrin-vascular endothelial growth factor (hnTf-VEGF) fusion protein containing an integrated binding site for (111)In for imaging tumour angiogenesis. J Nucl Med. 2005; 46(10): 1745-52.

LI S, PECK-RADOSAVLJEVIC M, KIENAST O, et. al. Iodine-123-vascular endothelial growth factor-165 (123I-VEGF165). Biodistribution, safety and radiation dosimetry in patients with pancreatic carcinoma. Q J Nucl Med Mol Imaging. 2004; 48(3): 198-206.

LU E, WAGNER WR, SCHELLENBERGER U, et. al. Targeted in vivo labelling of receptors for vascular endothelial growth factor: approach to identification of ischemic tissue. Circulation. 2003; 108(1): 97-103.

HAUBNER R, BEER AJ, WANG H, CHEN X. Positron emission tomography tracers for imaging angiogenesis. Eur J Nucl Med Mol Imaging. 2010; (37 Suppl 1): S86-103. [34] CAI W, CHEN K, MOHAMEDALI KA, et. al. PET of vascular endothelial growth factor receptor expression. J Nucl Med. 2006; 47(12): 2048-56.

NAGENGAST WB, HOOGE MN, van STRATEN EM, et. al. VEGF-SPECT with ¹¹¹In-bevacizumab in stage III/IV melanoma patients. Eur J Cancer. 2011; 47(10): 1595-602.

HOSSEINIMEHR SJ, ORLOVA A, TOLMACHEV V. Preparation and in vitro evaluation of 111In-CHX-A”-DTPA-labeled anti-VEGF monoclonal antibody bevacizumab. Hum Antibodies. 2010; 19(4): 107-11.

PAUDYAL B, PAUDYAL P, ORIUCHI N, et. al. Positron emission tomography imaging and biodistribution of vascular endothelial growth factor with 64Cu-labeled bevacizumab in colorectal cancer xenografts. Cancer Sci. 2011; 102(1): 117-21.

ASHRAFI SA, HOSSEINIMEHR SJ, VARMIRA K, ABEDI SM. Radioimmunotherapy with ¹³¹I-bevacizumab as a specificmolecule for cells with overexpression of the vascular endothelial growth factor. Cancer Biother Radiopharm. 2012; 27(7): 420-5.

GAYKEMA SB, SCHRÖDER CP, VITFELL-RASMUSSEN J, et. al. 89Zr-trastuzumab and 89Zr-bevacizumab PET to evaluate the effect of the HSP90 inhibitor NVP-AUY922 in metastatic breast cancer patients. Clin Cancer Res. 2014; 20(15): 3945-54.

KÄRRE K, LJUNGGREN HG, PIONTEK G, KIESSLING R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. J Immunol. 2005; 174(11): 6566-9.

SCHOTT M. Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers. Endocr Relat Cancer. 2006; 13(3): 779-95.

CHENG M, CHEN Y, XIAO W, et. al. NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol. 2013; 10(3): 230-52.

SHI Y, PARHAR RS, ZOU M, et. al. Gene therapy of anaplastic thyroid carcinoma with a single-chain interleukin-12 fusion protein. Hum Gene Ther. 2003; 14(18): 1741-51.

MELDER RJ, BROWNELL AL, SHOUP TM, et. al . Imaging of activated natural killer cells in mice by positron emission tomography: preferential uptake in tumours. Cancer Res. 1993; 53(24): 5867-71.

MEIER R, PIERT M, PIONTEK G, et. al. Tracking of [18F]FDG-labeled natural killer cells to HER2/neu-positive tumours. Nucl Med Biol. 2008; 35(5): 579-88.

MELLER B, FROHN C, BRAND JM, et. al. Monitoring of a new approach of immunotherapy with allogenic (111)In-labelled NK cells in patients with renal cell carcinoma. Eur J Nucl Med Mol Imaging. 2004; 31(3): 403-7.

MATERA L, GALETTO A, BELLO M, et. al. In vivo migration of labeled autologous natural killer cells to liver metastases in patients with colon carcinoma. J Transl Med. 2006; 4: 49.

SCHÄFER E, DUMMER R, EILLES C, et. al . Imaging pattern of radiolabeled lymphokine-activated killer cells in patients with metastatic malignant melanoma. Eur J Nucl Med. 1991; 18(2): 106-10.

GALLI F, HISTED S, ARAS O. NK cell imaging by in vitro and in vivo labelling approaches. Q J Nucl Med Mol Imaging. 2014; 58(3): 276-83.

NELSON BH. CD20+ B cells: the other tumour-infiltrating lymphocytes. J Immunol. 2010; 185(9): 4977-82.

CORONELLA-WOOD JA, HERSH EM. Naturally occurring B-cell responses to breast cancer. Cancer Immunol. Immunother. 2003; 52(12): 715-738.

CHIN Y, JANSEENS J, VANDEPITTE J, et. al. Phenotypic analysis of tumour-infiltrating lymphocytes from human breast cancer. Anticancer Res. 1992; 12(5): 1463-1466.

MARSIGLIANTE S, VISCOSO L, MARRA A, et. al. Computerised counting of tumour infiltrating lymphocytes in 90 breast cancer specimens. Cancer Lett. 1999; 139(1): 33-41.

GMEINER STOPAR T, FETTICH J, ZVER S, et. al. 99mTc-labelled rituximab, a new non-Hodgkin’s lymphoma imaging agent: first clinical experience. Nucl Med Común. 2008; 29(12): 1059-65.

MALVIYA G, ANZOLA KL, PODESTA E, et. al. (99m)Tc-labeled Rituximab for Imaging B Lymphocyte Infiltration in Inflammatory Autoimmune Disease Patients. Mol Imaging Biol. 2012; 14(5): 637-46.

DAVIS TA, KAMINSKI MS, LEONARD JP, et. al. The radioisotope contributes significantly to the activity of radioimmunotherapy. Clin Cancer Res. 2004; 10(23): 7792-7798.

IVANOV A, KRYSOV S, CRAGG MS, ILLIDGE T. Radiation therapy with tositumomab (B1) anti-CD20 monoclonal antibody initiates extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent cell death that overcomes resistance to apoptosis. Clin Cancer Res. 2008; 14(15): 4925-4934.

CURIEL TJ. Tregs and rethinking cancer immunotherapy. J Clin Invest. 2007; 117(5): 1167-74.

SIGNORE A, ANNOVAZZI A, BARONE R, et. al. 99mTc-interleukin-2 scintigraphy as a potential tool for evaluating tumour-infiltrating lymphocytes in melanoma lesions: a validation study. J Nucl Med. 2004; 45(10): 1647-52.

RENARD V, STAELENS L, SIGNORE A, et. al. Iodine-123-interleu-kin-2 scintigraphy in metastatic hypernephroma: a pilot study. Q J Nucl Med Mol Imaging. 2007; 51(4): 352-6.

LOOSE D, SIGNORE A, STAELENS L, et. al. (123) I-Interleukin-2 uptake in squamous cell carcinoma of the head and neck carcinoma. Eur J Nucl Med Mol Imaging. 2008; 35(2): 281-6.

SIGNORE A, CAPRIOTTI G, CHIANELLI M, et. al. Detection of insulitis by pancreatic scintigraphy with 99mTc-labeled IL-2 and MRI in patients with LADA (Action LADA 10). Diabetes Care. 2015; 38(4): 652-8.

CHIANELLI M, PARISELLA MG, VISALLI N, et. al. Pancreatic scintigraphy with 99mTc-interleukin-2 at diagnosis of type 1 diabetes and after 1 year of nicotinamide therapy. Diabetes Metab Res Rev. 2008; 24(2): 115-22.

ANNOVAZZI A, BIANCONE L, CAVIGLIA R, et. al. 99mTc-interleukin-2 and (99m)Tc-HMPAO granulocyte scintigraphy in patients with inactive Crohn’s disease. Eur J Nucl Med Mol Imaging. 2003; 30(3): 374-82.

SIGNORE A, CHIANELLI M, ANNOVAZZI A, et. al. Imaging active lymphocytic infiltration in coeliac disease with iodine-123-inter-leukin-2 and the response to diet. Eur J Nucl Med. 2000; 27(1): 18-24.

CHIANELLI M, MATHER SJ, GROSSMAN A, et. al. 99mTc-interleukin-2 scintigraphy in normal subjects and in patients with autoimmune thyroid diseases: a feasibility study. Eur J Nucl Med Mol Imaging. 2008; 35(12): 2286-93.