Gangming Cai

Preliminary studies of 99mTc-memantine derivatives for NMDA receptor imaging

INTRODUCTION Novel technetium-labeled ligands, (99m)Tc-NCAM and (99m)Tc-NHAM were developed from the N-methyl-d-aspartate (NMDA) receptor agonist memantine as a lead compound by coupling with N(2)S(2). This study evaluated the binding affinity and specificity of the ligands for the NMDA receptor. METHODS Ligand biodistribution and uptake specificity in the brain were investigated in mice. Binding affinity and specificity were determined by radioligand receptor binding assay. Three antagonists were used for competitive binding analysis. In addition, uptake of the complexes into SH-SY5Y nerve cells was evaluated. RESULTS The radiochemical purity of (99m)Tc-labeled ligands was more than 95%. Analysis of brain regional uptake showed higher concentration in the frontal lobe and specific uptake in the hippocampus. (99m)Tc-NCAM reached a higher target to nontarget ratio than (99m)Tc-NHAM. The results indicated that (99m)Tc-NCAM bound to a single site on the NMDA receptor with a K(d) of 701.21 nmol/l and a B(max) of 62.47 nmol/mg. Specific inhibitors of the NMDA receptor, ketamine and dizocilpine, but not the dopamine D(2) and 5HT(1A) receptor partial agonist aripiprazole, inhibited specific binding of (99m)Tc-NCAM to the NMDA receptor. Cell physiology experiments showed that NCAM can increase the viability of SH-SY5Y cells after glutamate-induced injury. CONCLUSIONS The new radioligand (99m)Tc-NCAM has good affinity for and specific binding to the NMDA receptor, and easily crosses the blood-brain barrier; suggesting that it might be a potentially useful tracer for NMDA receptor expression.

Preliminary evaluation of novel 18F-AlF-NOTA-IF7 as a tumor imaging agent

Annexin 1 (Anxa1) is a highly specific surface marker of tumor vasculature. A carbohydrate ligand-mimicking 7-mer peptide, IFLLWQR (Ile-Phe-Leu–Leu-Trp-Gln-Arg, IF7) can target Anxa1 in tumor vasculature. IF7 was first conjugated with a macrocyclic chelator, 1, 4, 7- triazacyclononane-1, 4, 7- triacetic acid (NOTA), and the resulting bioconjugate NOTA-IF7 was then radiofluorinated via Al18F intermediate to synthesize 18F-AlF-NOTA-IF7. MicroPET studies demonstrated that 18F-AlF-NOTA-IF7 had good uptake in tumor. 18F-AlF-NOTA-IF7 is a promising radiopharmaceutical in tumor imaging. The favorable characterizations of 18F-AlF-NOTA-IF7 such as convenient synthesis, specific Anxa1 targeting and moderate tumor uptake make it possible for imaging of cancers.

3-(2-Fluoro-phen-oxy)propanoic acid.

In the title compound, C9H9FO3, the dihedral angle between the carboxyl group and the benzene ring is 79.4 (3)°. In the crystal, molecules form centrosymmetric dimers through pairs of classical O—H⋯O hydrogen bonds. These are further linked by weaker C—H⋯O interactions, forming a three-dimensional network.