The Experts below are selected from a list of 29589 Experts worldwide ranked by ideXlab platform
Willem H. Bakker - One of the best experts on this subject based on the ideXlab platform.
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comparison of 111in labeled somatostatin analogues for tumor scintigraphy and radionuclide therapy
Cancer Research, 1998Co-Authors: M De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Leo J. Hofland, Ananth Srinivasan, Wouter A P Breeman, Peter P M Kooij, M Schmidt, Jack L ErionAbstract:We evaluated the following (111)In-labeled somatostatin (SS) analogues (diethylenetriaminepentaacetic acid, DTPA; tetraazacyclododecanetetraacetic acid, DOTA): [DTPA0]Octreotide, [DTPA0,Tyr3]Octreotide, [DTPA0,D-Tyr1]Octreotide, [DTPA0,Tyr3]octreotate [Thr(ol) in Octreotide replaced with Thr], and [DOTA0,Tyr3]Octreotide, in vitro and in vivo. In vitro, all compounds showed high and specific binding to SS receptors in mouse pituitary AtT20 tumor cell membranes, and IC50s were in the nanomolar range. Furthermore, all compounds showed specific internalization in rat pancreatic tumor cells; uptake of [(111)In-DTPA0,Tyr3]octreotate was the highest of the compounds tested, and that of [(111)In-DTPA0,D-Tyr1]Octreotide was the lowest. Biodistribution experiments in rats showed that, 4, 24, and 48 h after injection of [(111)In-DTPA0,Tyr3]Octreotide, [(111)In-DTPA0,Tyr3]octreotate, and [(111)In-DOTA0,Tyr3]Octreotide, radioactivity in the Octreotide-binding, receptor-expressing tissues and tumor-to-blood ratios were significantly higher than those after injection of [(111)In-DTPA0]Octreotide. Uptake of [(111)In-DTPA0,Tyr3]octreotate in the target organs was also, in vivo, the highest of the radiolabeled peptides tested, whereas that of [(111)In-DTPA0,D-Tyr1]Octreotide was the lowest. Uptake of [(111)In-DTPA0,Tyr3]Octreotide, [(111)In-DTPA0,Tyr3]octreotate, and [(111)In-DOTA0,Tyr3]Octreotide in target tissues was blocked by >90% by 0.5 mg of unlabeled Octreotide, indicating specific binding to the Octreotide receptors. Blockade of [(111)In-DTPA0,D-Tyr1]Octreotide was >70%. In conclusion, radiolabeled [DTPA0,Tyr3]Octreotide and, especially, [DTPA0,Tyr3]octreotate and their DOTA-coupled counterparts are most promising for scintigraphy and radionuclide therapy of SS receptor-positive tumors in humans.
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Pre-clinical comparison of [DTPA0] Octreotide, [DTPA0,Tyr3] Octreotide and [DOTA0,Tyr3] Octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
International journal of cancer, 1998Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Leo J. Hofland, Ananth Srinivasan, Michelle A. Schmidt, Martin Behe, Helmut R. MäckeAbstract:We have evaluated the potential usefulness of radiolabelled [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide as radiopharmaceuticals for somatostatin receptor-targeted scintigraphy and radiotherapy. In vitro somatostatin receptor binding and in vivo metabolism in rats of the compounds were investigated in comparison with [ III In-DTPA 0 ] Octreotide. Comparing different peptide-chelator constructs, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 , Tyr 3 ]Octreotide were found to have a higher affinity than [DTPA 0 ]Octreotide for subtype 2 somatostatin receptors (sst 2 ) in mouse AtT20 pituitary tumour cell membranes (all IC 50 values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both III In-labelled [DOTA 0 ,Tyr 3 ]Octreotide and [DTPA 0 ,Tyr 3 ]Octreotide in sst 2 -expressing tissues than after injection of [ III In-DTPA 0 ]Octreotide, showing that substitution of Tyr for Phe at position 3 in Octreotide results in an increased affinity for its receptor and in a higher target tissue uptake. Uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled Octreotide/rat, indicating specific binding to sst 2 . Comparing different radionuclides, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide had the highest uptake in sst 2 -positive organs, followed by the [ III In-DOTA 0 ,Tyr 3 ]Octreotide, whereas [DOTA 0 , 125 I-Try 3 ]Octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 , Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide was reduced over 50% by an i.v. injection of 400 mglkg D-lysine, whereas radioactivity in blood, pancreas and adrenals was not affected.
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Internalization of radiolabelled [DTPA0]Octreotide and [DOTA0,Tyr3]Octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
Nuclear medicine communications, 1998Co-Authors: M. De Jong, Bert F. Bernard, E. De Bruin, A. Van Gameren, Willem H. Bakker, Theo J. Visser, Helmut R. Mäcke, E. P. KrenningAbstract:We compared the internalization of [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide with that of [ 125 I-Tyr 3 ]Octreotide and [ 111 In-DTPA 0 ]Octreotide in the subtype 2 somatostatin receptor (sst 2 )-positive rat pancreatic tumour cell lines CA20948 and AR42J and in the somatostatin receptor-negative human anaplastic thyroid tumour cell line ARO. We demonstrated that [ 111 In-DTPA 0 ]Octreotide, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide are internalized by a receptor-specific, time- and temperature-dependent process. The amount of [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide internalized was higher than that of [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DTPA 0 ]Octreotide.
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yttrium 90 and indium 111 labelling receptor binding and biodistribution of dota0 d phe1 tyr3 Octreotide a promising somatostatin analogue for radionuclide therapy
European Journal of Nuclear Medicine and Molecular Imaging, 1997Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Martin Behe, Eric P. Krenning, Marcel E Van Der Pluijm, Eduard Jermann, Pia PowellAbstract:In vitro Octreotide receptor binding of [111In-DOTA0,d-Phe1,Tyr3]Octreotide (111In-DOTATOC) and the in vivo metabolism of90Y or111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]Octreotide [111In-DTPAOC).111In-DOTATOC was found to have an affinity similar to Octreotide itself for the Octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of90Y or111In-labelled DOTATOC, uptake of radioactivity in the Octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2–6 that after injection of111In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled Octreotide, indicating specific binding to the Octreotide receptors. These findings strongly indicate that90Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that111In-DOTATOC is of potential value for diagnosis of patients with Octreotide receptor-positive lesions, such as most neuroendocrine tumours.
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somatostatin receptor scintigraphy with indium 111 dtpa d phe 1 Octreotide in man metabolism dosimetry and comparison with iodine 123 tyr 3 Octreotide
The Journal of Nuclear Medicine, 1992Co-Authors: E. P. Krenning, Willem H. Bakker, Theo J. Visser, M De Jong, Wouter A P Breeman, Peter P M Kooij, C Bruns, H Y Oei, Jean Claude Reubi, D J KwekkeboomAbstract:Scintigraphy with 123I-Tyr-3-Octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-Octreotide, has consequently been proposed. DTPA-D-Phe-1-Octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-Octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-Octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-Octreotide and with 111In-DTPA-D-Phe-1-Octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-Octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-Octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.
Theo J. Visser - One of the best experts on this subject based on the ideXlab platform.
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comparison of 111in labeled somatostatin analogues for tumor scintigraphy and radionuclide therapy
Cancer Research, 1998Co-Authors: M De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Leo J. Hofland, Ananth Srinivasan, Wouter A P Breeman, Peter P M Kooij, M Schmidt, Jack L ErionAbstract:We evaluated the following (111)In-labeled somatostatin (SS) analogues (diethylenetriaminepentaacetic acid, DTPA; tetraazacyclododecanetetraacetic acid, DOTA): [DTPA0]Octreotide, [DTPA0,Tyr3]Octreotide, [DTPA0,D-Tyr1]Octreotide, [DTPA0,Tyr3]octreotate [Thr(ol) in Octreotide replaced with Thr], and [DOTA0,Tyr3]Octreotide, in vitro and in vivo. In vitro, all compounds showed high and specific binding to SS receptors in mouse pituitary AtT20 tumor cell membranes, and IC50s were in the nanomolar range. Furthermore, all compounds showed specific internalization in rat pancreatic tumor cells; uptake of [(111)In-DTPA0,Tyr3]octreotate was the highest of the compounds tested, and that of [(111)In-DTPA0,D-Tyr1]Octreotide was the lowest. Biodistribution experiments in rats showed that, 4, 24, and 48 h after injection of [(111)In-DTPA0,Tyr3]Octreotide, [(111)In-DTPA0,Tyr3]octreotate, and [(111)In-DOTA0,Tyr3]Octreotide, radioactivity in the Octreotide-binding, receptor-expressing tissues and tumor-to-blood ratios were significantly higher than those after injection of [(111)In-DTPA0]Octreotide. Uptake of [(111)In-DTPA0,Tyr3]octreotate in the target organs was also, in vivo, the highest of the radiolabeled peptides tested, whereas that of [(111)In-DTPA0,D-Tyr1]Octreotide was the lowest. Uptake of [(111)In-DTPA0,Tyr3]Octreotide, [(111)In-DTPA0,Tyr3]octreotate, and [(111)In-DOTA0,Tyr3]Octreotide in target tissues was blocked by >90% by 0.5 mg of unlabeled Octreotide, indicating specific binding to the Octreotide receptors. Blockade of [(111)In-DTPA0,D-Tyr1]Octreotide was >70%. In conclusion, radiolabeled [DTPA0,Tyr3]Octreotide and, especially, [DTPA0,Tyr3]octreotate and their DOTA-coupled counterparts are most promising for scintigraphy and radionuclide therapy of SS receptor-positive tumors in humans.
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Pre-clinical comparison of [DTPA0] Octreotide, [DTPA0,Tyr3] Octreotide and [DOTA0,Tyr3] Octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
International journal of cancer, 1998Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Leo J. Hofland, Ananth Srinivasan, Michelle A. Schmidt, Martin Behe, Helmut R. MäckeAbstract:We have evaluated the potential usefulness of radiolabelled [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide as radiopharmaceuticals for somatostatin receptor-targeted scintigraphy and radiotherapy. In vitro somatostatin receptor binding and in vivo metabolism in rats of the compounds were investigated in comparison with [ III In-DTPA 0 ] Octreotide. Comparing different peptide-chelator constructs, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 , Tyr 3 ]Octreotide were found to have a higher affinity than [DTPA 0 ]Octreotide for subtype 2 somatostatin receptors (sst 2 ) in mouse AtT20 pituitary tumour cell membranes (all IC 50 values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both III In-labelled [DOTA 0 ,Tyr 3 ]Octreotide and [DTPA 0 ,Tyr 3 ]Octreotide in sst 2 -expressing tissues than after injection of [ III In-DTPA 0 ]Octreotide, showing that substitution of Tyr for Phe at position 3 in Octreotide results in an increased affinity for its receptor and in a higher target tissue uptake. Uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled Octreotide/rat, indicating specific binding to sst 2 . Comparing different radionuclides, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide had the highest uptake in sst 2 -positive organs, followed by the [ III In-DOTA 0 ,Tyr 3 ]Octreotide, whereas [DOTA 0 , 125 I-Try 3 ]Octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 , Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide was reduced over 50% by an i.v. injection of 400 mglkg D-lysine, whereas radioactivity in blood, pancreas and adrenals was not affected.
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Internalization of radiolabelled [DTPA0]Octreotide and [DOTA0,Tyr3]Octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
Nuclear medicine communications, 1998Co-Authors: M. De Jong, Bert F. Bernard, E. De Bruin, A. Van Gameren, Willem H. Bakker, Theo J. Visser, Helmut R. Mäcke, E. P. KrenningAbstract:We compared the internalization of [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide with that of [ 125 I-Tyr 3 ]Octreotide and [ 111 In-DTPA 0 ]Octreotide in the subtype 2 somatostatin receptor (sst 2 )-positive rat pancreatic tumour cell lines CA20948 and AR42J and in the somatostatin receptor-negative human anaplastic thyroid tumour cell line ARO. We demonstrated that [ 111 In-DTPA 0 ]Octreotide, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide are internalized by a receptor-specific, time- and temperature-dependent process. The amount of [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide internalized was higher than that of [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DTPA 0 ]Octreotide.
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yttrium 90 and indium 111 labelling receptor binding and biodistribution of dota0 d phe1 tyr3 Octreotide a promising somatostatin analogue for radionuclide therapy
European Journal of Nuclear Medicine and Molecular Imaging, 1997Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Martin Behe, Eric P. Krenning, Marcel E Van Der Pluijm, Eduard Jermann, Pia PowellAbstract:In vitro Octreotide receptor binding of [111In-DOTA0,d-Phe1,Tyr3]Octreotide (111In-DOTATOC) and the in vivo metabolism of90Y or111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]Octreotide [111In-DTPAOC).111In-DOTATOC was found to have an affinity similar to Octreotide itself for the Octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of90Y or111In-labelled DOTATOC, uptake of radioactivity in the Octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2–6 that after injection of111In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled Octreotide, indicating specific binding to the Octreotide receptors. These findings strongly indicate that90Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that111In-DOTATOC is of potential value for diagnosis of patients with Octreotide receptor-positive lesions, such as most neuroendocrine tumours.
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somatostatin receptor scintigraphy with indium 111 dtpa d phe 1 Octreotide in man metabolism dosimetry and comparison with iodine 123 tyr 3 Octreotide
The Journal of Nuclear Medicine, 1992Co-Authors: E. P. Krenning, Willem H. Bakker, Theo J. Visser, M De Jong, Wouter A P Breeman, Peter P M Kooij, C Bruns, H Y Oei, Jean Claude Reubi, D J KwekkeboomAbstract:Scintigraphy with 123I-Tyr-3-Octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-Octreotide, has consequently been proposed. DTPA-D-Phe-1-Octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-Octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-Octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-Octreotide and with 111In-DTPA-D-Phe-1-Octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-Octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-Octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.
Bert F. Bernard - One of the best experts on this subject based on the ideXlab platform.
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comparison of 111in labeled somatostatin analogues for tumor scintigraphy and radionuclide therapy
Cancer Research, 1998Co-Authors: M De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Leo J. Hofland, Ananth Srinivasan, Wouter A P Breeman, Peter P M Kooij, M Schmidt, Jack L ErionAbstract:We evaluated the following (111)In-labeled somatostatin (SS) analogues (diethylenetriaminepentaacetic acid, DTPA; tetraazacyclododecanetetraacetic acid, DOTA): [DTPA0]Octreotide, [DTPA0,Tyr3]Octreotide, [DTPA0,D-Tyr1]Octreotide, [DTPA0,Tyr3]octreotate [Thr(ol) in Octreotide replaced with Thr], and [DOTA0,Tyr3]Octreotide, in vitro and in vivo. In vitro, all compounds showed high and specific binding to SS receptors in mouse pituitary AtT20 tumor cell membranes, and IC50s were in the nanomolar range. Furthermore, all compounds showed specific internalization in rat pancreatic tumor cells; uptake of [(111)In-DTPA0,Tyr3]octreotate was the highest of the compounds tested, and that of [(111)In-DTPA0,D-Tyr1]Octreotide was the lowest. Biodistribution experiments in rats showed that, 4, 24, and 48 h after injection of [(111)In-DTPA0,Tyr3]Octreotide, [(111)In-DTPA0,Tyr3]octreotate, and [(111)In-DOTA0,Tyr3]Octreotide, radioactivity in the Octreotide-binding, receptor-expressing tissues and tumor-to-blood ratios were significantly higher than those after injection of [(111)In-DTPA0]Octreotide. Uptake of [(111)In-DTPA0,Tyr3]octreotate in the target organs was also, in vivo, the highest of the radiolabeled peptides tested, whereas that of [(111)In-DTPA0,D-Tyr1]Octreotide was the lowest. Uptake of [(111)In-DTPA0,Tyr3]Octreotide, [(111)In-DTPA0,Tyr3]octreotate, and [(111)In-DOTA0,Tyr3]Octreotide in target tissues was blocked by >90% by 0.5 mg of unlabeled Octreotide, indicating specific binding to the Octreotide receptors. Blockade of [(111)In-DTPA0,D-Tyr1]Octreotide was >70%. In conclusion, radiolabeled [DTPA0,Tyr3]Octreotide and, especially, [DTPA0,Tyr3]octreotate and their DOTA-coupled counterparts are most promising for scintigraphy and radionuclide therapy of SS receptor-positive tumors in humans.
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Pre-clinical comparison of [DTPA0] Octreotide, [DTPA0,Tyr3] Octreotide and [DOTA0,Tyr3] Octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
International journal of cancer, 1998Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Leo J. Hofland, Ananth Srinivasan, Michelle A. Schmidt, Martin Behe, Helmut R. MäckeAbstract:We have evaluated the potential usefulness of radiolabelled [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide as radiopharmaceuticals for somatostatin receptor-targeted scintigraphy and radiotherapy. In vitro somatostatin receptor binding and in vivo metabolism in rats of the compounds were investigated in comparison with [ III In-DTPA 0 ] Octreotide. Comparing different peptide-chelator constructs, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 , Tyr 3 ]Octreotide were found to have a higher affinity than [DTPA 0 ]Octreotide for subtype 2 somatostatin receptors (sst 2 ) in mouse AtT20 pituitary tumour cell membranes (all IC 50 values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both III In-labelled [DOTA 0 ,Tyr 3 ]Octreotide and [DTPA 0 ,Tyr 3 ]Octreotide in sst 2 -expressing tissues than after injection of [ III In-DTPA 0 ]Octreotide, showing that substitution of Tyr for Phe at position 3 in Octreotide results in an increased affinity for its receptor and in a higher target tissue uptake. Uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled Octreotide/rat, indicating specific binding to sst 2 . Comparing different radionuclides, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide had the highest uptake in sst 2 -positive organs, followed by the [ III In-DOTA 0 ,Tyr 3 ]Octreotide, whereas [DOTA 0 , 125 I-Try 3 ]Octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 , Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide was reduced over 50% by an i.v. injection of 400 mglkg D-lysine, whereas radioactivity in blood, pancreas and adrenals was not affected.
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Internalization of radiolabelled [DTPA0]Octreotide and [DOTA0,Tyr3]Octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
Nuclear medicine communications, 1998Co-Authors: M. De Jong, Bert F. Bernard, E. De Bruin, A. Van Gameren, Willem H. Bakker, Theo J. Visser, Helmut R. Mäcke, E. P. KrenningAbstract:We compared the internalization of [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide with that of [ 125 I-Tyr 3 ]Octreotide and [ 111 In-DTPA 0 ]Octreotide in the subtype 2 somatostatin receptor (sst 2 )-positive rat pancreatic tumour cell lines CA20948 and AR42J and in the somatostatin receptor-negative human anaplastic thyroid tumour cell line ARO. We demonstrated that [ 111 In-DTPA 0 ]Octreotide, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide are internalized by a receptor-specific, time- and temperature-dependent process. The amount of [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide internalized was higher than that of [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DTPA 0 ]Octreotide.
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yttrium 90 and indium 111 labelling receptor binding and biodistribution of dota0 d phe1 tyr3 Octreotide a promising somatostatin analogue for radionuclide therapy
European Journal of Nuclear Medicine and Molecular Imaging, 1997Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Martin Behe, Eric P. Krenning, Marcel E Van Der Pluijm, Eduard Jermann, Pia PowellAbstract:In vitro Octreotide receptor binding of [111In-DOTA0,d-Phe1,Tyr3]Octreotide (111In-DOTATOC) and the in vivo metabolism of90Y or111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]Octreotide [111In-DTPAOC).111In-DOTATOC was found to have an affinity similar to Octreotide itself for the Octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of90Y or111In-labelled DOTATOC, uptake of radioactivity in the Octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2–6 that after injection of111In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled Octreotide, indicating specific binding to the Octreotide receptors. These findings strongly indicate that90Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that111In-DOTATOC is of potential value for diagnosis of patients with Octreotide receptor-positive lesions, such as most neuroendocrine tumours.
M. De Jong - One of the best experts on this subject based on the ideXlab platform.
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Pre-clinical comparison of [DTPA0] Octreotide, [DTPA0,Tyr3] Octreotide and [DOTA0,Tyr3] Octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
International journal of cancer, 1998Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Leo J. Hofland, Ananth Srinivasan, Michelle A. Schmidt, Martin Behe, Helmut R. MäckeAbstract:We have evaluated the potential usefulness of radiolabelled [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide as radiopharmaceuticals for somatostatin receptor-targeted scintigraphy and radiotherapy. In vitro somatostatin receptor binding and in vivo metabolism in rats of the compounds were investigated in comparison with [ III In-DTPA 0 ] Octreotide. Comparing different peptide-chelator constructs, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 , Tyr 3 ]Octreotide were found to have a higher affinity than [DTPA 0 ]Octreotide for subtype 2 somatostatin receptors (sst 2 ) in mouse AtT20 pituitary tumour cell membranes (all IC 50 values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both III In-labelled [DOTA 0 ,Tyr 3 ]Octreotide and [DTPA 0 ,Tyr 3 ]Octreotide in sst 2 -expressing tissues than after injection of [ III In-DTPA 0 ]Octreotide, showing that substitution of Tyr for Phe at position 3 in Octreotide results in an increased affinity for its receptor and in a higher target tissue uptake. Uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled Octreotide/rat, indicating specific binding to sst 2 . Comparing different radionuclides, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide had the highest uptake in sst 2 -positive organs, followed by the [ III In-DOTA 0 ,Tyr 3 ]Octreotide, whereas [DOTA 0 , 125 I-Try 3 ]Octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 , Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide was reduced over 50% by an i.v. injection of 400 mglkg D-lysine, whereas radioactivity in blood, pancreas and adrenals was not affected.
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Internalization of radiolabelled [DTPA0]Octreotide and [DOTA0,Tyr3]Octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
Nuclear medicine communications, 1998Co-Authors: M. De Jong, Bert F. Bernard, E. De Bruin, A. Van Gameren, Willem H. Bakker, Theo J. Visser, Helmut R. Mäcke, E. P. KrenningAbstract:We compared the internalization of [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide with that of [ 125 I-Tyr 3 ]Octreotide and [ 111 In-DTPA 0 ]Octreotide in the subtype 2 somatostatin receptor (sst 2 )-positive rat pancreatic tumour cell lines CA20948 and AR42J and in the somatostatin receptor-negative human anaplastic thyroid tumour cell line ARO. We demonstrated that [ 111 In-DTPA 0 ]Octreotide, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide are internalized by a receptor-specific, time- and temperature-dependent process. The amount of [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide internalized was higher than that of [ 111 In-DOTA 0 ,Tyr 3 ]Octreotide and [ 111 In-DTPA 0 ]Octreotide.
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yttrium 90 and indium 111 labelling receptor binding and biodistribution of dota0 d phe1 tyr3 Octreotide a promising somatostatin analogue for radionuclide therapy
European Journal of Nuclear Medicine and Molecular Imaging, 1997Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Martin Behe, Eric P. Krenning, Marcel E Van Der Pluijm, Eduard Jermann, Pia PowellAbstract:In vitro Octreotide receptor binding of [111In-DOTA0,d-Phe1,Tyr3]Octreotide (111In-DOTATOC) and the in vivo metabolism of90Y or111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]Octreotide [111In-DTPAOC).111In-DOTATOC was found to have an affinity similar to Octreotide itself for the Octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of90Y or111In-labelled DOTATOC, uptake of radioactivity in the Octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2–6 that after injection of111In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled Octreotide, indicating specific binding to the Octreotide receptors. These findings strongly indicate that90Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that111In-DOTATOC is of potential value for diagnosis of patients with Octreotide receptor-positive lesions, such as most neuroendocrine tumours.
Leo J. Hofland - One of the best experts on this subject based on the ideXlab platform.
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comparison of 111in labeled somatostatin analogues for tumor scintigraphy and radionuclide therapy
Cancer Research, 1998Co-Authors: M De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Leo J. Hofland, Ananth Srinivasan, Wouter A P Breeman, Peter P M Kooij, M Schmidt, Jack L ErionAbstract:We evaluated the following (111)In-labeled somatostatin (SS) analogues (diethylenetriaminepentaacetic acid, DTPA; tetraazacyclododecanetetraacetic acid, DOTA): [DTPA0]Octreotide, [DTPA0,Tyr3]Octreotide, [DTPA0,D-Tyr1]Octreotide, [DTPA0,Tyr3]octreotate [Thr(ol) in Octreotide replaced with Thr], and [DOTA0,Tyr3]Octreotide, in vitro and in vivo. In vitro, all compounds showed high and specific binding to SS receptors in mouse pituitary AtT20 tumor cell membranes, and IC50s were in the nanomolar range. Furthermore, all compounds showed specific internalization in rat pancreatic tumor cells; uptake of [(111)In-DTPA0,Tyr3]octreotate was the highest of the compounds tested, and that of [(111)In-DTPA0,D-Tyr1]Octreotide was the lowest. Biodistribution experiments in rats showed that, 4, 24, and 48 h after injection of [(111)In-DTPA0,Tyr3]Octreotide, [(111)In-DTPA0,Tyr3]octreotate, and [(111)In-DOTA0,Tyr3]Octreotide, radioactivity in the Octreotide-binding, receptor-expressing tissues and tumor-to-blood ratios were significantly higher than those after injection of [(111)In-DTPA0]Octreotide. Uptake of [(111)In-DTPA0,Tyr3]octreotate in the target organs was also, in vivo, the highest of the radiolabeled peptides tested, whereas that of [(111)In-DTPA0,D-Tyr1]Octreotide was the lowest. Uptake of [(111)In-DTPA0,Tyr3]Octreotide, [(111)In-DTPA0,Tyr3]octreotate, and [(111)In-DOTA0,Tyr3]Octreotide in target tissues was blocked by >90% by 0.5 mg of unlabeled Octreotide, indicating specific binding to the Octreotide receptors. Blockade of [(111)In-DTPA0,D-Tyr1]Octreotide was >70%. In conclusion, radiolabeled [DTPA0,Tyr3]Octreotide and, especially, [DTPA0,Tyr3]octreotate and their DOTA-coupled counterparts are most promising for scintigraphy and radionuclide therapy of SS receptor-positive tumors in humans.
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Pre-clinical comparison of [DTPA0] Octreotide, [DTPA0,Tyr3] Octreotide and [DOTA0,Tyr3] Octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy.
International journal of cancer, 1998Co-Authors: M. De Jong, Bert F. Bernard, Willem H. Bakker, Theo J. Visser, Wout A. P. Breeman, Leo J. Hofland, Ananth Srinivasan, Michelle A. Schmidt, Martin Behe, Helmut R. MäckeAbstract:We have evaluated the potential usefulness of radiolabelled [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide as radiopharmaceuticals for somatostatin receptor-targeted scintigraphy and radiotherapy. In vitro somatostatin receptor binding and in vivo metabolism in rats of the compounds were investigated in comparison with [ III In-DTPA 0 ] Octreotide. Comparing different peptide-chelator constructs, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 , Tyr 3 ]Octreotide were found to have a higher affinity than [DTPA 0 ]Octreotide for subtype 2 somatostatin receptors (sst 2 ) in mouse AtT20 pituitary tumour cell membranes (all IC 50 values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both III In-labelled [DOTA 0 ,Tyr 3 ]Octreotide and [DTPA 0 ,Tyr 3 ]Octreotide in sst 2 -expressing tissues than after injection of [ III In-DTPA 0 ]Octreotide, showing that substitution of Tyr for Phe at position 3 in Octreotide results in an increased affinity for its receptor and in a higher target tissue uptake. Uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 ,Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled Octreotide/rat, indicating specific binding to sst 2 . Comparing different radionuclides, [ 90 Y-DOTA 0 ,Tyr 3 ]Octreotide had the highest uptake in sst 2 -positive organs, followed by the [ III In-DOTA 0 ,Tyr 3 ]Octreotide, whereas [DOTA 0 , 125 I-Try 3 ]Octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of III In-labelled [DTPA 0 ]Octreotide, [DTPA 0 , Tyr 3 ]Octreotide and [DOTA 0 ,Tyr 3 ]Octreotide was reduced over 50% by an i.v. injection of 400 mglkg D-lysine, whereas radioactivity in blood, pancreas and adrenals was not affected.
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111in dtpa d phe1 Octreotide a potential radiopharmaceutical for imaging of somatostatin receptor positive tumors synthesis radiolabeling and in vitro validation
Life Sciences, 1991Co-Authors: Willem H. Bakker, Leo J. Hofland, Wouter A P Breeman, R Albert, C Bruns, P Marbach, J Pless, D Pralet, B Stolz, Jan W KoperAbstract:Abstract Somatostatin receptor-positive human tumors can be detected using radioiodinated analogues of somatostatin, both in vitro and in vivo. [123I-Tyr3]-Octreotide has been successfully used in the visualization of somatostatin receptor-positive tumors by gamma camera scintigraphy, but this radiopharmaceutical has some major drawbacks, which can be overcome with other radionuclides such as 111In. As starting material for a potentially convenient radiopharmaceutical, a diethylenetriaminopentaacetic acid (DTPA) conjugated derivative of Octreotide (SMS 201–995) was prepared. This peptide, [DTPA-D-Phe1]-Octreotide (SDZ 215-811) binds more than 95 % of added 111In in an easy, single-step labeling procedure without necessity of further purification. The specific somatostatin-like biologic effect of these analogues was proven by the inhibition of growth hormone secretion by cultured rat pituitary cells in a dose-dependent fashion by Octreotide, [DTPA-D-Phe1]-Octreotide and non-radioactive [115In-DTPA-D-Phe1]-Octreotide. The binding of [111In-DTPA-D-Phe1]-Octreotide to rat brain cortex membranes proved to be displaced similarly by natural somatostatin as well as by Octreotide, suggesting specific binding of [111In-DTPA-D-Phe1]-Octreotide to somatostatin receptors. The binding of the indium-labeled compound showed a somewhat lower affinity when compared with the iodinated [Tyr3]-Octreotide, but indium-labeled [DTPA-D-Phe1]-Octreotide still binds with nanomolar affinity. In conjunction with in vivo studies, these results suggest that [111In-DTPA-D-Phe1]-Octreotide is a promising radiopharmaceutical for scintigraphic imaging of somatostatin receptor-positive tumors.
