PRECLINICAL 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

Citation
M. Dejong et al., PRECLINICAL 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, International journal of cancer, 75(3), 1998, pp. 406-411
Citations number
22
Categorie Soggetti
Oncology
ISSN journal
00207136
Volume
75
Issue
3
Year of publication
1998
Pages
406 - 411
Database
ISI
SICI code
0020-7136(1998)75:3<406:PCO[O[>2.0.ZU;2-2
Abstract
We have evaluated the potential usefulness of radiolabelled [DTPA(0),T yr(3)]octreotide and [DOTA(0),Tyr(3)]octreotide as radiopharmaceutical s 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 [In-111-DTPA(0)] o ctreotide, Comparing different peptide-chelator constructs, [DTPA(0),T yr(3)]octreotide and [DOTA(0),Tyr(3)]octreotide were found to have a h igher affinity than [DTPA(0)]octreotide for subtype 2 somatostatin rec eptors (sst(2)) in mouse AtT20 pituitary tumour cell membranes (all IC 50 values obtained were in the low nanomolar range), In vivo studies i n CA20948 tumor-bearing Lewis rats revealed a significantly higher upt ake of both In-111-labelled [DOTA(0),Tyr(3)]octreotide and [DTPA(0),Ty r(3)]octreotide in sst(2)-expressing tissues than after injection of [ In-111-DTPA(0)]octreotide, showing that substitution of Tyr for Phe at position 3 in octreotide results in an increased affinity for its rec eptor and in a higher target tissue uptake, Uptake of In-111-labelled [DTPA(0)]octreotide, [DTPA(0),Tyr(3)]octreotide and [DOTA(0),Tyr(3)]oc treotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled octreo tide/rat, indicating specific binding to sst(2), Comparing different r adionuclides, [Y-90-DOTA(0),Tyr(3)]octreotide had the highest uptake i n sst(2)-positive organs, followed by the [In-111-DOTA(0),Tyr(3)]octre otide, whereas [DOTA(0),I-125-Try(3)]octreotide uptake was low compare d to that of the other radiopharmaceuticals, when measured 24 hr after injection, Renal uptake of In-111-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.