Three chemical modification methods of carboxymethylation, quaternization and hydroxypropylation were used to synthesize water-soluble chitosan derivatives. In order to study the feasibility of these chitosan derivatives as backbones of nuclear imaging agents, folic acid (FA) and Technetium-99m were introduced onto the water-soluble chitosan chains. The bifunctional chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to the folate grafted chitosan derivatives for chelating with radionuclides such as 64Cu and 68Ga. The structures of these new ligands were characterized with multiple methods. The solubility and stability of the 99mTc-complexes were both favorable. Further study of their radiochemical and biological properties will be performed to evaluate the usefulness of these water-soluble chitosan derivatives for nuclear imaging agent design.

The (2-methoxyphenyl) piperazine (MPP) was selected as the functional group and conjugated to dithiocarbamate through different spacers. A series of new MPP derivatives (MPPnDTC, n = 2–6) were synthesized and radiolabelled with 99mTc-nitrido core or 99mTc-tricarboxyl core as potential 5-HT1A receptor imaging agents. All the six 99mTc-labelled complexes were lipophilic and neutral. Biodistribution results showed that those radiotracers had moderate initial brain and hippocampus uptake. There have no significant relation was observed between the biological properties of these tracers with the length of its carbon chain. The radioactivity concentrations of hippocampus of 99mTcN-MPP2DTC, 99mTcN-MPP3DTC, 99mTcN-MPP4DTC, 99mTcN-MPP5DTC, 99mTcN-MPP6DTC and 99mTc(CO)3-MPP3DTC at 2 min post-injection time (p.i.) were 0.43, 1.15, 0.99, 1.04, 1.13 and 0.83 %ID/g, respectively.

5-HT1A receptor is associated with a variety of pathophysiology of neuropsychiatric disorders. Accordingly, we have synthesized a new 5-HT1A receptor ligand (HYNIC-MPP4) and labeled it with 99mTc using N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA) as coligand. 99mTc-HEDTA/HYNIC-MPP4 was prepared under pH 6 at room temperature. Biodistribution of 99mTc-HEDTA/HYNIC-MPP4 in normal mice showed that this complex had moderate brain uptake (0.60% ID·g−1 at 2 min p.i.) and good retention. The hippocampus had the highest radioactivity uptake at 2 min p.i. (1.84% ID⋆g−1). The ratio of Hipp/CB was 3.1 at 2 min p.i. and increased to 4.4 at 60 min p.i. After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 1.84% ID·g−1 to 0.53% ID·g−1 at 2 min p.i., while the cerebellum had no significant decrease. This 99mTc complex could be a potent agent for 5-HT1A receptor imaging.