Pharmacokinetics of 99mTc-labeled oligonucleotides

Oligonucleotides labeled with gamma-emitting radionuclides are likely to find eventual applications as radiopharmaceuticals. Accordingly, methods of radiolabeling single-stranded DNA by chelation with the gamma-emitting radionuclide 111In and, more importantly, with 99mTc, have been developed. As an emerging technology, the results of only two pharmacokinetic investigations with 99mTc-labeled DNA have been reported thus far, both from this laboratory. This review focuses on the pharmacokinetic properties in mice of 99mTc when radiolabeled by one method (SHNH) to a 22-base native phosphodiester and phosphorothioate DNA. The labeled phosphodiester DNA displayed an affinity for proteins through its 99mTc-SHNH chelate. The affinity for proteins of the labeled phosphorothioate DNA was even greater and was attributed in this case to both the chelate and to the modified, and lipophilic, DNA backbone. As a consequence of this binding, and the recognized increased stability of the phosphorothioate DNA towards nucleases, probably explained the long-term retention of label in organs such as liver, spleen and kidney. In conclusion, under the conditions of these investigations, the labeled phosphodiester and phosphorothioate DNAs studied were both judged to be unsuitable for most applications as radiopharmaceuticals.