Synthesis and biodistribution of 64Cu and 68Ga radiolabelled dendritic polyglycerol sulfate derivatives


Synthesis and biodistribution of 64Cu and 68Ga radiolabelled dendritic polyglycerol sulfate derivatives

Pant, K.; Stephan, H.; Bergmann, R.; Steinbach, J.; Gröger, D.; Haag, R.

Dendrimers and their hyper-branched analogues, particularly highly biocompatible polyglycerols, claim an interesting area of research due to their multivalency, simplicity in preparation and large scale one-pot synthesis. They can be modified and functionalized using manifold strategies. Dendritic polyglycerol sulfates (dPGS) are potent substances that serve as candidates for anti-inflammatory drugs [1]. The presence of amino functionalities can be further exploited for the introduction of fluorescent dyes, drugs, radiolabels or any moiety of interest. To achieve detailed information about the in vivo fate of certain compounds, nuclear imaging techniques are the most reliable methodologies. Ex vivo imaging using 35S–isotopic labelling of these macromolecules has already been reported [2]. Positron emission tomography (PET) provides quantitative distribution data in vivo. The convenient detection of the emitted radiation from the radionuclides in combination with the high sensitivity underlines the utility of nuclear imaging techniques. If a metal is used as a radiolabel, the choice of an appropriate bifunctional chelator (BFC) is the crucial point. The BFCs shall permit an easy linkage to the polymers and rapid, unsophisticated, stable labelling.
Herein, protocols for the attachment of BFCs for the positron emitting radionuclides 64Cu (t1/2 = 12.7h) and 68Ga ((t1/2 = 68 min) on dPGS scaffolds are reported. For this reason, derivatives based on 1,4-bis(2-pyridylmethyl)-1,4,7-triazacyclononane (DMPTACN) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) equipped with suitable linker groups have been applied. Efficient radiolabelling procedures have been established (>99% RCY). The stability of the radiolabelled bioconjugates has been studied in presence of strong competing chelators (EDTA/Cyclam) as well as in presence of HSA (human serum albumin), SOD[3] (for Cu-Conjugates) and transferrin (for Ga-conjugates). Furthermore, PET studies using Wistar rats have been performed and discussed.

References
[1] J. Demedde, A. Rausch, M.Weinhart, S. Enders, R. Tauber, K. Licha, M. Schimer, U. Zugel, A. von Bonin, R. Haag, Proc. Natl. Acad. Sci. 107, 19679 (2010).
[2] C. Holzhausen, D. Groger, L. Mundhenk, P. Welker, R. Haag, A. D. Gruber, Nanomed. 9,

  • Lecture (Conference)
    5th EuCheMS Chemistry Congress, 31.08.-04.09.2014, Istanbul, Turkey

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