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Tissue distribution and metabolism of radioiodinated DTPA0, D-Tyr1 and Tyr3 derivatives of octreotide in rats.

Abstract：

UNLABELLED:Lesions containing somatostatin receptors (SSR) in rats and in man can be visualized in vivo using radiolabeled octreotide (OCT) analogs. SSR scintigraphy was initially performed with [123I-Tyr3]OCT and later with [111In-DTRA0]OCT. With the latter the residence time of radioactivity (111In) in SSR-positive targets is prolonged, most probably due to the DTPA group. Therefore, we hypothesized that its presence might also affect the metabolism of radioiodinated DTPA-OCT analogs. [D-Tyr1]OCT, [DTPA0, D-Tyr1]OCT, [Tyr3]OCT and [DTPA0,Tyr3]OCT were synthesized, and all 4 showed high and specific binding to the SSR in vitro, with IC50 values in the nanomolar range. The rate of internalization of the 4 radioiodinated OCT analogs by mouse AtT20 pituitary tumors cells was in accordance with the IC50 values. The metabolism and tissue distribution of the 4 radioiodinated analogs were investigated in rats at 4, 24 and 48 hours pi, and the tissue vs blood ratios were calculated. High uptake of all OCT analogs was found in the somatostatin receptor-positive tissues at 4 hours, but only remained high at 24 and 48 hours with [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT. Kidney uptake of [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT was also high. Blood clearance and disappearance from muscle was rapid for all 4 analogs. Urinary excretion of [125I-D-Tyr1]OCT, [DTPA0,125I-D-Tyr1]OCT,[125I-Tyr3]OCT and [DTPA0, 125I-Tyr3]OCT amounted to 63%, 67%, 31% and 80% of injected dose respectively. [DTPA0,125I-D-Tyr1]OCT showed highest tissue to blood ratio and residence time in SSR-positive tissues, such as adrenals (ratio: 31, 79, and 66 at 4, 24 and 48 hours respectively) and pancreas (ratio: 14, 48 and 44 at 4, 24 and 48 hours respectively). CONCLUSION:The position of the Tyr residues and the addition of the DTPA group greatly influence the biodistribution of radioiodinated [Tyr]OCT analogs.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Breeman WA,de Jong M,Bernard B,Hofland LJ,Srinivasan A,van der Pluijm M,Bakker WH,Visser TJ,Krenning EP

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

83-9

issue

eissn

0250-7005

issn

1791-7530

journal_volume

pub_type

杂志文章

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Tissue distribution and metabolism of radioiodinated DTPA0, D-Tyr1 and Tyr3 derivatives of octreotide in rats.