Crucial role for somatostatin receptor subtype 2 in determining the uptake of [111In-DTPA-D-Phe1]octreotide in somatostatin receptor-positive organs

Leo J. Hofland*, Steven W.J. Lamberts, P. Martin van Hagen, Jean Claude Reubi, James Schaeffer, Marlijn Waaijers, Peter M. Van Koetsveld, Ananth Srinivasan, Eric P. Krenning, Wout A.P. Breeman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

68 Citations (Scopus)


Human somatostatin (SS) receptor (sst)-positive tumors can be visualized by gamma camera scintigraphy after the injection of [111In- diethylenetriaminepentaacetic acid (DTPA)-D-Phe1] octreotide. Uptake of [111In-DTPA-D-Phe1]octreotide is dependent on sst-mediated internalization of the radioligand by the tumor cells. Human sst-positive tumors frequently express multiple sst subtypes. In vitro studies have demonstrated that the 5 sst subtypes (ssti1-5) differentially internalize sst-bound ligand. The present study was performed to evaluate the role of sst2 in vivo in determining the uptake of [ 111In-DTPA-D-Phe1]octreotide, as well as of the more "universal" ligand [111In-DTPA]SS-14, by sst-positive organs expressing multiple sst subtypes. Methods: Wild-type and sst2 knockout mice (n = 4 per treatment group) were injected intravenously with 1 MBq (0.1 μg) [111In-DTPA-D-Phe1]octreotide or [ 111In-DTPA]SS-14. After 24 h, the animals were sacrificed and radioactivity in the organs under investigation was determined. In addition, the sst subtype messenger RNA (mRNA) expression pattern in these organs was determined by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Results: RT-PCR analysis demonstrated the presence of all 5 sst subtype mRNAs in the adrenals and pituitary of wild-type mice but no sst2 in the knockout mice. The thymus expressed mRNA for sst2 and sst4 mRNA in wild-type mice, whereas no sst2 was detected in knockout mice. In wildtype mice, the in vivo uptake values (in percentage injected dose per gram of tissue) of [111In-DTPA-D-Phe1]octreotide for the pituitary, adrenals, pancreas, and thymus amounted to 1.2 ± 0.2, 0.26 ± 0.03, 0.18 ± 0.03, and 0.30 ± 0.05, respectively, in wild-type mice. Compared with wild-type mice, sst2 knockout mice had dramatically lower uptake values in these organs - lower by 97%, 83%, 96%, and 94%, respectively (P < 0.01 vs. wild type). Comparable differences in the uptake of radioactivity between wild-type and knockout mice were found using [111In-DTPA]SS-14 as the radiotracer. Interestingly, in some organs expressing sst2 mRNA (liver, muscle, and peripheral blood mononuclear cells), no specific binding of [111In-DTPA-D-Phe1] octreotide or [111In-DTPA]SS-14 to sst in vivo was found, suggesting that the sst2 protein expression level was very low in these tissues. Conclusion: The uptake of [111In-DTPA-D-Phe1]octreotide and [111In-DTPA]SS-14 in sst-positive organs is determined predominantly by sst2.

Original languageEnglish
Pages (from-to)1315-1321
Number of pages7
JournalJournal of Nuclear Medicine
Issue number8
Publication statusPublished - Aug 2003


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