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Pre‐clinical comparison of [DTPA 0 ] octreotide, [DTPA 0 ,Tyr 3 ] octreotide and [DOTA 0 ,Tyr 3 ] octreotide as carriers for somatostatin receptor‐targeted scintigraphy and radionuclide therapy
Author(s) -
De Jong Marion,
Bakker Willem H.,
Breeman Wout A. P.,
Bernard Bert F.,
Hofland Leo J.,
Visser Theo J.,
Srinivasan Ananth,
Schmidt Michelle,
Béhé Martin,
Mäcke Helmut R.,
Krenning Eric P.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980130)75:3<406::aid-ijc14>3.0.co;2-6
Subject(s) - octreotide , somatostatin , somatostatin receptor , endocrinology , medicine , radionuclide therapy
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 [ 111 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 111 In‐labelled [DOTA 0 ,Tyr 3 ]octreotide and [DTPA 0 ,Tyr 3 ]octreotide in sst 2 ‐expressing tissues than after injection of [ 111 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 111 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 [ 111 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 111 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 mg/kg d‐lysine, whereas radioactivity in blood, pancreas and adrenals was not affected. Int. J. Cancer 75:406–411, 1998. © 1998 Wiley‐Liss, Inc.