Inhomogeneous activity distribution of 177Lu-DOTA0-Tyr3-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice

详细信息    查看全文

• 作者：Jenny Oddstig (1)
  Peter Bernhardt (1)
  Helena Lizana (1)
  Ola Nilsson (2)
  H?kan Ahlman (3)
  Lars K?lby (3)
  Eva Forssell-Aronsson (1)
  
• 关键词：Radionuclide therapy ; Somatostatin receptors ; [177Lu ; DOTA0 ; Tyr3] ; octreotate ; Midgut carcinoid ; Dosimetry
• 刊名：Tumor Biology
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：33
• 期：1
• 页码：229-239
• 全文大小：433KB
• 参考文献：1. De Jong M, Valkema R, Jamar F, Kvols LK, Kwekkeboom DJ, Breeman WA, Bakker WH, Smith C, Pauwels S, Krenning EP. Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. Semin Nucl Med. 2002;32(2):133-0. CrossRef
  2. Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, O'Dorisio TM, Valkema R, Bodei L, Chinol M, Maecke HR, Krenning EP. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med. 2005;46 Suppl 1:62S-S.
  3. Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooij PP, de Herder WW, Feelders RA, van Eijck CH, Esser JP, Kam BL, Krenning EP. Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol. 2005;23(12):2754-2. CrossRef
  4. Sw?rd C, Bernhardt P, Ahlman H, Wangberg B, Forssel-Aronsson E, Larsson M, Svensson J, Rossi-Norrlund R, Kolby L. [177Lu-DOTA 0-Tyr 3]-octreotate treatment in patients with disseminated gastroenteropancreatic neuroendocrine tumors: the value of measuring absorbed dose to the kidney. World J Surg. 2010;34(6):1368-2. CrossRef
  5. Van Essen M, Krenning EP, De Jong M, Valkema R, Kwekkeboom DJ. Peptide receptor radionuclide therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol. 2007;46(6):723-4. CrossRef
  6. Andersson P, Forssell-Aronsson E, Johanson V, W?ngberg B, Nilsson O, Fj?lling M, Ahlman H. Internalization of indium-111 into human neuroendocrine tumor cells after incubation with indium-111-DTPA-D-Phe1-octreotide. J Nucl Med. 1996;37(12):2002-.
  7. De Jong M, Bernard BF, De Bruin E, Van Gameren A, Bakker WH, Visser TJ, Macke HR, Krenning EP. Internalization of radiolabelled [DTPA0]octreotide and [DOTA0, Tyr3]octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy. Nucl Med Commun. 1998;19(3):283-. CrossRef
  8. Hofland LJ, van Koetsveld PM, Waaijers M, Lamberts SW. Internalisation of isotope-coupled somatostatin analogues. Digestion. 1996;57 Suppl 1:2-. CrossRef
  9. Storch D, Behe M, Walter MA, Chen J, Powell P, Mikolajczak R, Macke HR. Evaluation of [99mTc/EDDA/HYNIC0]octreotide derivatives compared with [111In-DOTA0, Tyr3, Thr8]octreotide and [111In-DTPA0]octreotide: does tumor or pancreas uptake correlate with the rate of internalization? J Nucl Med. 2005;46(9):1561-.
  10. Draznin B, Sherman N, Sussman K, Dahl R, Vatter A. Internalization and cellular processing of somatostatin in primary culture of rat anterior pituitary cells. Endocrinology. 1985;117(3):960-. CrossRef
  11. Morel G, Pelletier G, Heisler S. Internalization and subcellular distribution of radiolabeled somatostatin-28 in mouse anterior pituitary tumor cells. Endocrinology. 1986;119(5):1972-. CrossRef
  12. Behe M, Koller S, Püsken M, Gross M, Alfke H, Keil B. Irradiation-induced upregulation of somatostatin and gastrin receptors in vitro and in vivo. Eur J Nucl Med Mol Imaging. 2004;31:S237-.
  13. Oddstig J, Bernhardt P, Nilsson O, Ahlman H, Forssell-Aronsson E. Radiation-induced up-regulation of somatostatin receptor expression in small cell lung cancer in vitro. Nucl Med Biol. 2006;33(7):841-. CrossRef
  14. Bernhardt P, Oddstig J, K?lby L, Nilsson O, Ahlman H, Forssell-Aronsson E. Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice. Cancer Biother Radiopharm. 2007;22(5):644-3. CrossRef
  15. Capello A, Krenning E, Bernard B, Reubi JC, Breeman W, de Jong M. 111In-labelled somatostatin analogues in a rat tumour model: somatostatin receptor status and effects of peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2005;32(11):1288-5. CrossRef
  16. Melis M, Forrer F, Capello A, Bijster M, Bernard BF, Reubi JC, Krenning EP, De Jong M. Up-regulation of somatostatin receptor density on rat CA20948 tumors escaped from low dose [(177)Lu-DOTA(0), Tyr(3)]octreotate therapy. Q J Nucl Med Mol Imaging. 2007;51(4):324-3.
  17. K?lby L, Bernhardt P, Ahlman H, W?ngberg B, Johanson V, Wigander A, Forssell-Aronsson E, Karlsson S, Ahren B, Stenman G, Nilsson O. A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake. Am J Pathol. 2001;158(2):745-5. CrossRef
  18. Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, Macke HR. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000;27(3):273-2. CrossRef
  19. Reubi JC, Waser B, Schaer JC, Laissue JA. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001;28(7):836-6. CrossRef
  20. de Jong M, Breeman WA, Bernard BF, Bakker WH, Schaar M, van Gameren A, Bugaj JE, Erion J, Schmidt M, Srinivasan A, Krenning EP. [177Lu-DOTA(0), Tyr3] octreotate for somatostatin receptor-targeted radionuclide therapy. Int J Cancer. 2001;92(5):628-3. CrossRef
  21. Schmitt A, Bernhardt P, Nilsson O, Ahlman H, K?lby L, Maecke HR, Forssell-Aronsson E. Radiation therapy of small cell lung cancer with 177Lu-DOTA-Tyr3-octreotate in an animal model. J Nucl Med. 2004;45(9):1542-.
  22. Bernhardt P, Forssell-Aronsson E, Jacobsson L, Skarnemark G. Low-energy electron emitters for targeted radiotherapy of small tumours. Acta Oncol. 2001;40(5):602-. CrossRef
  23. Uusij?rvi HCN, Bernhardt P, Ferrer L, Bardiès M, Forssell-Aronsson E. Comparison of electron dose-point kernels in water generated by the Monte Carlo codes, PENELOPE, GEANT4, MCNPX, and ETRAN. Cancer Biother Radiopharm. 2009;24(4):461-. CrossRef
  24. Salvat F, Fernándes-Varea J, Sempau J. PENELOPE-2006: a code system for Monte Carlo simulations of electron and photon transport. Paris: OECD Nuclear Energy Agency; 2006.
  25. Browne E, Firestone R. Table of radioactive isotopes. New York: Wiley/Interscience; 1986.
  26. K?lby L, Bernhardt P, Johanson V, Schmitt A, Ahlman H, Forssell-Aronsson E, M?cke H, Nilsson O. Successful receptor-mediated radiation therapy of xenografted human midgut carcinoid tumour. Br J Cancer. 2005;93(10):1144-1. CrossRef
  27. Nordberg ESA, Persson M, Sundberg AL, Carlsson J, Glimelius B. Cellular uptake of radioiodine delivered by trastuzumab can be modified by the addition of epidermal growth factor. Eur J Nucl Med Mol Imaging. 2005;32(7):771-. CrossRef
  28. Thurber GM, Schmidt MM, Wittrup KD. Factors determining antibody distribution in tumors. Trends Pharmacol Sci. 2008;29(2):57-1.
  29. Thurber GM, Zajic SC, Wittrup KD. Theoretic criteria for antibody penetration into solid tumors and micrometastases. J Nucl Med. 2007;48(6):995-. CrossRef
  30. Williams L, Bares R, Fass J, Hauptmann S, Schumpelick V, Buell U. Uptake of radiolabeled anti-CEA antibodies in human colorectal primary tumors as a function of tumor mass. Eur J Nucl Med. 1993;20(4):345-. CrossRef
  31. Williams L, Duda R, Proffitt R, Beatty B, Beatty D, Wong J, Shively J, Paxton R. Tumor uptake as a function of tumor mass: a mathematic model. J Nucl Med. 1988;29(1):103-.
  32. Sw?rd C, Bernhardt P, Johanson V, Schmitt A, Ahlman H, Stridsberg M, Forssell-Aronsson E, Nilsson O, K?lby L. Comparison of [177Lu-DOTA0, Tyr3]-octreotate and [177Lu-DOTA0, Tyr3]-octreotide for receptor-mediated radiation therapy of the xenografted human midgut carcinoid tumor GOT1. Cancer Biother Radiopharm. 2008;23(1):114-0. CrossRef
  33. Forssell-Aronsson E, Bernhardt P, Nilsson O, Tisell LE, W?ngberg B, Ahlman H. Biodistribution data from 100 patients i.v. injected with 111In-DTPA-D-Phe1-octreotide. Acta Oncol. 2004;43(5):436-2. CrossRef
  
• 作者单位：Jenny Oddstig (1)
  Peter Bernhardt (1)
  Helena Lizana (1)
  Ola Nilsson (2)
  H?kan Ahlman (3)
  Lars K?lby (3)
  Eva Forssell-Aronsson (1)
  
  1. Department of Radiation Physics, Lundberg Laboratory for Cancer Research, University of Gothenburg, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
  2. Department of Pathology, Lundberg Laboratory for Cancer Research, University of Gothenburg, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
  3. Department of Surgery, Lundberg Laboratory for Cancer Research, University of Gothenburg, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
  
• ISSN：1423-0380

文摘

The aim of this study was to investigate the activity distribution in neouroendocrine tumors after diagnostic, or therapeutic, amounts of [177Lu-DOTA0-Tyr3]-octreotate and to investigate how the activity distribution influences the absorbed dose. Furthermore, the activity distribution of a second administration of radiolabeled octreotate was studied. Nude mice with subcutaneously grown human midgut carcinoid (GOT1) were injected intravenously with different amounts of 177Lu-octreotate. At different time points thereafter (4?h to 13?days), a second injection of [111In-DOTA0-Tyr3]-octreotate was given to estimate the somatostatin receptor (sstr) expression. The activity distribution in the tumors was then determined. Monte Carlo simulations with PENELOPE were performed for dosimetry. Fifty-one out of 58 investigated tumors showed a lower activity concentration in the peripheral part than in the central part of the tumor. The amount of activity injected, or time after administration, did neither influence the relative activity nor the sstr distribution in the tumor. After an initial down-regulation (at 4-4?h), there was an up-regulation of sstr (1.5- times, at 7-4?days). Monte Carlo simulations demonstrated an inhomogeneous absorbed dose distribution in the tumor using 177Lu, with twice as high absorbed dose centrally than peripherally. The high activity concentration centrally and the up-regulation of sstr demonstrated will facilitate fractionated therapy using radiolabeled somatostatin analogues if similar results will be obtained also in patients. The inhomogeneous activity distribution in the tumor has to be taken into account when the absorbed dose distribution in tumor is calculated.