Biodistribution and catabolism of 18F-labeled neurotensin(8–13) analogs
4-([ 18F]fluoro)benzoyl-neurotensin(8–13) ( 18FB-Arg 8-Arg 9-Pro 10-Tyr 11- Ile 12-Leu 13-OH, 1) and two analogs stabilized in one and two positions ( 18FB-Arg 8ψ(CH 2NH)Arg 9-Pro 10-Tyr 11- Ile 12-Leu 13-OH, 2, 18FB-Arg 8ψ(CH 2NH)Arg 9-Pro 10-Tyr 11-Tle 12-Leu 13-OH, 3) were synthesized in a radioc...
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Published in | Nuclear medicine and biology Vol. 29; no. 1; pp. 61 - 72 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier Inc
2002
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | 4-([
18F]fluoro)benzoyl-neurotensin(8–13) (
18FB-Arg
8-Arg
9-Pro
10-Tyr
11- Ile
12-Leu
13-OH,
1) and two analogs stabilized in one and two positions (
18FB-Arg
8ψ(CH
2NH)Arg
9-Pro
10-Tyr
11- Ile
12-Leu
13-OH,
2,
18FB-Arg
8ψ(CH
2NH)Arg
9-Pro
10-Tyr
11-Tle
12-Leu
13-OH,
3) were synthesized in a radiochemical yield of 25–36% and a specific activity of 5–15 GBq/mmol. The peptides were evaluated
in vitro and
in vivo for their potential to image tumors overexpressing neurotensin receptor 1 (NTR1) by positron emission tomography (PET). All analogs exhibited
in vitro binding affinity in the low nanomolar range to NTR1-expressing human tumors, measured by quantitative receptor autoradiography, HT-29 and WiDr cells, and to sections of tumors derived from these cell lines in mice. The radiotracers were internalized in the cells
in vitro, and the fluorinated peptides were able to mobilize intracellular Ca
2+ of WiDr cells. In
in vivo studies in rats and in mice bearing HT-29 cell tumors, only a moderate uptake of the radioligands into the studied tumors was observed, presumingly due to degradation
in vivo and fast elimination by the kidneys. In comparison with the other analogs, the specific tumor uptake expressed as tumor-to-muscle relation was highest for the radioligand 3. The blood clearance of 3 was reduced by co-injection of peptidase inhibitors. The catabolic pathways of the radiofluorinated peptides were elucidated. The results suggest that the high binding affinity to NTR1 and the stabilization against proteolytic degradation are not yet sufficient for tumor imaging by PET. |
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ISSN: | 0969-8051 1872-9614 |
DOI: | 10.1016/S0969-8051(01)00284-0 |