Aiming to design radioactive compounds based on the core “99mTc(CO)3” for probing inducible nitric oxide synthase (iNOS) levels in vivo, we have synthesized conjugates containing a pyrazolyl-diamine chelating unit and pendant L-arginine analogues (substrates and inhibitors of NOS). Reaction of the conjugates with fac-[M(CO)3]+ (M = Re, 99mTc) gave bioorganometallic complexes of the type fac-[M(CO)3(k3-L)] in good yield. After in vitro testing using the oxyhemoglobin NO capture assay, we concluded that the affinity of the inhibitor-containing conjugates to iNOS seems to be less affected upon metallation with rhenium than the substrate-containing conjugates. The complexes bearing guanidino substituted analogues of L-arginine still present considerable inhibitory action (Nω-monomethyl-L-arginine, Ki = 36 μM; Nω-nitro-L-arginine, Ki = 84 μM), being the first examples of organometallic complexes able to inhibit the iNOS. These results seem to indicate that 99mTc(CO)3-labeled L-argininine analogues, namely NOS inhibitors, may hold potential for monitoring increased levels of iNOS in vivo.
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