Pre-clinical comparison of [DTPA0] octreotide, [DTPA0,Tyr3] octreotide and [DOTA0,Tyr3] octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy
✍ Scribed by Marion De Jong; Willem H. Bakker; Wout A. P. Breeman; Bert F. Bernard; Leo J. Hofland; Theo J. Visser; Ananth Srinivasan; Michelle Schmidt; Martin Béhé; Helmut R. Mäcke; Eric P. Krenning
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 124 KB
- Volume
- 75
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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.