Pre-clinical comparison of [DTPA0] octreotide, [DTPA0,Tyr3] octreotide and [DOTA0,Tyr3] octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy

Int J Cancer. 1998 Jan 30;75(3):406-11. doi: 10.1002/(sici)1097-0215(19980130)75:3<406::aid-ijc14>;2-6.


We have evaluated the potential usefulness of radiolabelled [DTPA0,Tyr3]octreotide and [DOTA0,Tyr3]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 [111In-DTPA0] octreotide. Comparing different peptide-chelator constructs, [DTPA0,Tyr3]octreotide and [DOTA0,Tyr3]octreotide were found to have a higher affinity than [DTPA0]octreotide for subtype 2 somatostatin receptors (sst2) in mouse AtT20 pituitary tumour cell membranes (all IC50 values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both 111In-labelled [DOTA0,Tyr3]octreotide and [DTPA0,Tyr3]octreotide in sst2-expressing tissues than after injection of [111In-DTPA0]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 111In-labelled [DTPA0]octreotide, [DTPA0,Tyr3]octreotide and [DOTA0,Tyr3]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 sst2. Comparing different radionuclides, [90Y-DOTA0,Tyr3]octreotide had the highest uptake in sst2-positive organs, followed by the [111In-DOTA0,Tyr3]octreotide, whereas [DOTA0,125I-Try3]octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of 111In-labelled [DTPA0]octreotide, [DTPA0,Tyr3]octreotide and [DOTA0,Tyr3]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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Carriers
  • Heterocyclic Compounds / pharmacokinetics
  • Heterocyclic Compounds / pharmacology
  • Heterocyclic Compounds, 1-Ring*
  • Indium Radioisotopes / administration & dosage
  • Iodine Radioisotopes / administration & dosage
  • Isotope Labeling
  • Kidney / metabolism
  • Male
  • Mice
  • Octreotide / analogs & derivatives*
  • Octreotide / pharmacokinetics
  • Octreotide / pharmacology
  • Pentetic Acid / pharmacokinetics
  • Pentetic Acid / pharmacology
  • Radioisotopes / administration & dosage*
  • Radiopharmaceuticals / metabolism
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / pharmacology*
  • Rats
  • Rats, Inbred Lew
  • Rats, Wistar
  • Receptors, Somatostatin / metabolism*
  • Tissue Distribution
  • Yttrium Radioisotopes / administration & dosage


  • Drug Carriers
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • Indium Radioisotopes
  • Iodine Radioisotopes
  • Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • Yttrium Radioisotopes
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Pentetic Acid
  • Octreotide