UZH-Logo

Preparation, 99mTc-labeling and biodistribution studies of a PNA oligomer containing a new ligand derivative of 2,2'-dipicolylamine


Gasser, G; Jaeger, K; Zenker, M; Bergmann, R; Steinbach, J; Stephan, H; Metzler-Nolte, N (2010). Preparation, 99mTc-labeling and biodistribution studies of a PNA oligomer containing a new ligand derivative of 2,2'-dipicolylamine. Journal of Inorganic Biochemistry, 104(11):1133-1140.

Abstract

Anew azido derivative of 2,2 `-dipicolylamine (Dpa), 2-azido-N,N-bis((pyridin-2-yl)methyl)ethanamine, (Dpa-N-3) was readily prepared from the known 2-(bis(pyridin-2-ylmethyl)amino)ethanol (Dpa-OH). It was demonstrated that Dpa-N-3 could be efficiently labeled with both Re(CO)(3)(H2O)(3)]Br and Tc-99m(H2O)(3)(CO)(3)] to give Re(CO)(3)(Dpa-N-3)]Br and Tc-99m(CO)(3)(Dpa-N-3)](+), respectively. Furthermore, Dpa-N3 was successfully coupled, on the solid phase, to a Peptide Nucleic Acid (PNA) oligomer (H-4-pentynoic acid-spacer-spacer-tgca-tgca-tgca-Lys-NH2; spacer = -NH-(CH2)(2)-O-(CH2)(2)-O-CH2-CO-) using the Cu(I)-catalyzed 2 + 3] azide/alkyne cycloaddition (Cu-AAC, often referred to as the prototypical ``click'' reaction) to give the Dpa-PNA oligomer. Subsequent labeling of Dpa-PNA with Tc-99m(H2O)(3)(CO)(3)](+) afforded Tc-99m(CO)(3)(Dpa-PNA)] in radiochemical yields > 90%. Partitioning experiments in a 1-octanol/water system were carried out to get more insight on the lipophilicity of Tc-99m(CO)(3)(Dpa-N-3)(+) and Tc-99m(CO)(3)(Dpa-PNA)]. Both compounds were found rather hydrophilic (log D-o/w values at pH = 7.4 are -0.50: Tc-99m(CO)(3)(Dpa-N-3)](+) and 0.85: Tc-99m(CO)(3)(Dpa-PNA)]. Biodistribution studies of Tc-99m(CO)(3)(Dpa-PNA)] in Wistar rats showed a very fast blood clearance (0.26 +/- 0.1 SUV, 1 h p.i.) and modest accumulation in the kidneys (5.45 +/- 0.45 SUV, 1 h p.i.). There was no significant activity in the thyroid and the stomach, demonstrating a high in vivo stability of the Tc-99m-labeled Dpa-PNA conjugate. (C) 2010 Elsevier Inc. All rights reserved.

Anew azido derivative of 2,2 `-dipicolylamine (Dpa), 2-azido-N,N-bis((pyridin-2-yl)methyl)ethanamine, (Dpa-N-3) was readily prepared from the known 2-(bis(pyridin-2-ylmethyl)amino)ethanol (Dpa-OH). It was demonstrated that Dpa-N-3 could be efficiently labeled with both Re(CO)(3)(H2O)(3)]Br and Tc-99m(H2O)(3)(CO)(3)] to give Re(CO)(3)(Dpa-N-3)]Br and Tc-99m(CO)(3)(Dpa-N-3)](+), respectively. Furthermore, Dpa-N3 was successfully coupled, on the solid phase, to a Peptide Nucleic Acid (PNA) oligomer (H-4-pentynoic acid-spacer-spacer-tgca-tgca-tgca-Lys-NH2; spacer = -NH-(CH2)(2)-O-(CH2)(2)-O-CH2-CO-) using the Cu(I)-catalyzed 2 + 3] azide/alkyne cycloaddition (Cu-AAC, often referred to as the prototypical ``click'' reaction) to give the Dpa-PNA oligomer. Subsequent labeling of Dpa-PNA with Tc-99m(H2O)(3)(CO)(3)](+) afforded Tc-99m(CO)(3)(Dpa-PNA)] in radiochemical yields > 90%. Partitioning experiments in a 1-octanol/water system were carried out to get more insight on the lipophilicity of Tc-99m(CO)(3)(Dpa-N-3)(+) and Tc-99m(CO)(3)(Dpa-PNA)]. Both compounds were found rather hydrophilic (log D-o/w values at pH = 7.4 are -0.50: Tc-99m(CO)(3)(Dpa-N-3)](+) and 0.85: Tc-99m(CO)(3)(Dpa-PNA)]. Biodistribution studies of Tc-99m(CO)(3)(Dpa-PNA)] in Wistar rats showed a very fast blood clearance (0.26 +/- 0.1 SUV, 1 h p.i.) and modest accumulation in the kidneys (5.45 +/- 0.45 SUV, 1 h p.i.). There was no significant activity in the thyroid and the stomach, demonstrating a high in vivo stability of the Tc-99m-labeled Dpa-PNA conjugate. (C) 2010 Elsevier Inc. All rights reserved.

Citations

25 citations in Web of Science®
28 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 03 Mar 2011
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:November 2010
Deposited On:03 Mar 2011 16:03
Last Modified:05 Apr 2016 14:52
Publisher:Elsevier
ISSN:0162-0134
Publisher DOI:10.1016/j.jinorgbio.2010.06.011
PubMed ID:20674031
Other Identification Number:ISI:000282193700001
Permanent URL: http://doi.org/10.5167/uzh-47373

Download

[img]Filetype: PDF - Registered users only
Size: 1MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations