TY - JOUR T1 - Crucial Role for Somatostatin Receptor Subtype 2 in Determining the Uptake of [<sup>111</sup>In-DTPA-<span class="sc">d</span>-Phe<sup>1</sup>]Octreotide in Somatostatin Receptor–Positive Organs JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1315 LP - 1321 VL - 44 IS - 8 AU - Leo J. Hofland AU - Steven W.J. Lamberts AU - P. Martin van Hagen AU - Jean-Claude Reubi AU - James Schaeffer AU - Marlijn Waaijers AU - Peter M. van Koetsveld AU - Ananth Srinivasan AU - Eric P. Krenning AU - Wout A.P. Breeman Y1 - 2003/08/01 UR - http://jnm.snmjournals.org/content/44/8/1315.abstract N2 - 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 (sst1–5) 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 wild-type 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 &lt; 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. ER -