Sparr C, Purkayastha N, Yoshinari T, Seebach D, Maschauer S, Prante O, Hübner H, Gmeiner P, Kolesinska B, Cescato R, Waser B, Reubi JC (2013)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2013
Original Authors: Sparr C., Purkayastha N., Yoshinari T., Seebach D., Maschauer S., Prante O., Hubner H., Gmeiner P., Kolesinska B., Cescato R., Waser B., Reubi J.C.
Publisher: Wiley-VCH Verlag / Wiley-Blackwell
Book Volume: 10
Pages Range: 2101-2121
Journal Issue: 12
Neurotensin(8-13) (NTS(8-13)) analogs with C- and/or N-terminal β-amino acid residues and three DOTA derivatives thereof have been synthesized (i.e., 1-6). A virtual docking experiment showed almost perfect fit of one of the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivatives, 6a, into a crystallographically identified receptor NTSR1 (Fig. 1). The affinities for the receptors of the NTS analogs and derivatives are low, when determined with cell-membrane homogenates, while, with NTSR1-exhibiting cancer tissues, affinities in the single-digit nanomolar range can be observed (Table 2). Most of the β-amino acid-containing NTS(8-13) analogs (Table 1 and Fig. 2), including the Ga complexes of the DOTA-substituted ones (6; Figs. 2 and 5), are stable for ca. 1 h in human serum and plasma, and in murine plasma. The biodistributions of two Ga complexes (of 6a and 6b) in HT29 tumor-bearing nude mice, in the absence and in the presence of a blocking compound, after 10, 30, and 60 min (Figs. 3 and 4) lead to the conclusion that the amount of specifically bound radioligand is rather low. This was confirmed by PET-imaging experiments with the tumor-bearing mice (Fig. 6). Comparison of the in vitro plasma stability (after 1 h) with the ex vivo blood content (after 10-15 min) of the two Ga complexes shows that they are rapidly cleaved in the animals (Fig. 5). Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.
APA:
Sparr, C., Purkayastha, N., Yoshinari, T., Seebach, D., Maschauer, S., Prante, O.,... Reubi, J.C. (2013). Syntheses, receptor bindings, in vitro and in vivo stabilities and biodistributions of DOTA-neurotensin(8-13) derivatives containing β-amino acid residues - A lesson about the importance of animal experiments. Chemistry & Biodiversity, 10(12), 2101-2121. https://dx.doi.org/10.1002/cbdv.201300331
MLA:
Sparr, Christof, et al. "Syntheses, receptor bindings, in vitro and in vivo stabilities and biodistributions of DOTA-neurotensin(8-13) derivatives containing β-amino acid residues - A lesson about the importance of animal experiments." Chemistry & Biodiversity 10.12 (2013): 2101-2121.
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