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
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
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.