We compared intemalization of three radioiodinated octreotide (OCT) somatostatin (SS) analogs[125I-Tyr3]OCT, [DTPA°,125I-Tyr3]OCT, and [DOTA°,125I-Tyr3]OCT - by somatostatin receptor (SSR)-positive mouse AtT20 pituitary tumor cells and human insulinoma cells. The three SS analogs were internalized in a specific, time-dependent manner. Internalization was significantly inhibited by pertussis toxin (100 μg/l) by 38%, 43%, and 31%, and by an inhibitor of receptor-mediated endocytosis (phenyl arsine oxide; 10 μM) by 98%, 94%, and 92%, respectively. Binding affinities of the three radioligands were comparable (0.2, 0.2, and 0.3 nM, respectively). However, [DOTA°,125I-Tyr3]OCT was internalized in a five-fold higher amount in comparison with the two other radioligands. A comparably high uptake of [DOTA°,125I-Tyr3]OCT was found in SSR-positive organs (pituitary, pancreas, and adrenals) in vivo in rats (a ten-fold, five-fold, and eight- fold higher uptake 4 hr post injection, respectively, compared with the two other radioligands). This resulted in very high target-background ratios for [DOTA°,125I-Tyr3]OCT 4 hr post injection amounting to 274, 566, and 623 in the pituitary, adrenals, and pancreas, respectively. Both in vivo and in vitro there was a rapid dissociation of radioactivity from the SSR-positive cells. Main conclusions are that: 1) coupling of chelating groups like DTPA or DOTA to the SS analog [Tyr3]OCT does not prevent the internalization of OCT after binding to SSRs; 2) [DOTA°,125I-Tyr3]OCT is internalized in a significantly higher amount by AtT20 and human insulinoma cells and in vivo in rats in SSR-positive organs, in comparison with [DTPA°,125I-Tyr3]OCT and [125I-Tyr3]OCT; and 3) the very high target-background ratios in vivo make radioiodinated [DOTA°,Tyr3]OCT a very suitable ligand for SSR-targeted radioguided surgery of SSR-positive human neuroendocrine tumors.

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doi.org/10.1046/j.1525-1381.1999.09110.x, hdl.handle.net/1765/69707
Proceedings of the Association of American Physicians
Department of Internal Medicine

Hofland, L.J, Breeman, W.A.P, Krenning, E.P, de Jong, M, Waaijers, M, van Koetsveld, P.M, … Lamberts, S.W.J. (1999). Internalization of [DOTA°,125I-Tyr3]Octreotide by somatostatin receptor-positive cells in vitro and in vivo: Implications for somatostatin receptor-targeted radioguided surgery. In Proceedings of the Association of American Physicians (Vol. 111, pp. 63–69). doi:10.1046/j.1525-1381.1999.09110.x