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- W4254037662 abstract "Tumours depend on sufficient blood supply for their growth. They are able to promote new blood vessel formation (neoangiogenesis) via angiogenic factors. Inhibition of this process results in tumour involution or necrosis. RGD (Arg-Gly-Asp) peptides are described to antagonise neoangiogenesis, e.g., by binding to αvβ3 receptors on blood vessels. In order to visualise neoangiogenesis in tumours in vitro and in vivo, we introduced and tested an RGD analogue [c(Arg-Gly-Asp-D-Tyr-Lys)], coupled to the chelator diethyleletriamepentaacetic acid (DTPA). This analogue can be radiolabelled with both 111In and 125I. In autoradiography and immunohistochemistry studies, the 125I-labelled analogue appeared to bind specifically and with high affinity to αvβ3 receptors on neovascular blood vessel sections of different major human cancers, like prostate and breast cancer, which express these receptors. This radioiodinated radiopharmaceutical also bound to and internalised in human carcinoid Bon cells and rat pancreatic CA20948 tumour cells. Internalisation was receptor-specific and appeared to be time and temperature dependent. In vivo in rats, we investigated administration of different peptide amounts (0.1, 0.5, and 100 μg). The best amount of the radiolabelled analogue to be administered to rats appeared to be 0.1 μg/rat, as uptake decreased with increasing peptide amount. We also found receptor-specific accumulation of the 111In-labelled analogue in the transplantable pancreatic tumour CA20948. The introduction of the DTPA group in this peptide resulted in renal clearance of the radiopharmaceutical, in contrast to the non-DTPA-conjugated compound that is cleared predominantly via the liver. 111In emits Auger and conversion electrons besides gamma radiation, therefore, this radiopharmaceutical is suitable not only for tumour scintigraphy but also has potential for radionuclide therapy of major human cancers as well. Moreover, after coupling to the chelator DOTA, the analogue could be radiolabelled in a stable way with β-emitters, e.g., 90Y and 177Lu, enlarging its potential. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 186–198 (2000). © 2000 Wiley-Liss, Inc." @default.
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- W4254037662 date "2000-08-20" @default.
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- W4254037662 title "Evaluation of a radiolabelled cyclic DTPA‐RGD analogue for tumour imaging and radionuclide therapy" @default.
- W4254037662 doi "https://doi.org/10.1002/1097-0215(20000820)90:4<186::aid-ijc2>3.3.co;2-g" @default.
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