RESEARCH ARTICLE

 

Modelling of the blood plasma species of biguanide derivatives exhibiting potential as diagnostic radiopharmaceuticals

 

 

Judith M. Wagener^{I, *} ; Midred K. Dithebe^I; Daniel Mogano^II; Ignacy Cukrowski^II; Jan Rijn Zeevaart^III

^IRadiochemistry, NECSA, P.O. Box 582, Pretoria 0001, South Africa
^IIDepartment of Chemistry, University of Pretoria, Pretoria 0002, South Africa
^IIICARST, North West University, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa

 

 

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ABSTRACT

^99mTc-DMSA (DMSA=dimercaptosuccinic acid), the gold standard for static renal imaging, has a long uptake time, which is a limiting factor in diagnostic procedures and also leads to a relatively high radiation dose to patients. The ligands dimethyl biguanide (DMBG), biuret (BIU), 2-imino-4-thiobiuret (ITB) and carboxy-biguanide (CBIG) have nitrogen donor atoms, which are able to complex transition elements. The formation constants needed in order to establish a blood plasma model for these ligands were determined by potentiometry and the results are reported herein. Based on blood plasma modelling, it was shown that the ligands had selectivity for ^99mTc over blood plasma metal ions at physiological pH and it was therefore hypothesized that the Tc-ligand complex would survive in blood plasma. Furthermore, no or few side effects related to the mobilization of blood plasma metal ions by these ligands are expected, once the radiopharmaceutical has been administered. It is also expected that these ligands should clear rapidly from the blood plasma.

Keywords: Biguanides, kidney agents, stability formation constants, blood plasma speciation, CBIG, DMBG, BIU, ITB

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Received 5 November 2007
Revised 15 April 2008
Accepted 30 April 2008

 

 

* To whom correspondence should be addressed. E-mail: jwagener@necsa.co.za