Preparation And Biological Evaluation Of^99mTc-labeled Tanaproget Deirvative As Nonsteroidal Progesterone Receptor Imaging Agent

Tanaproget is a new type of nonsteroidal progesterone receptor (PR) regulator, highselectivity and relative compatibility for PR.As tanaproget analogue,5-{4-[3-(Bis-pyridin-2-ylmethyl-amino)-propyl]-4-methyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl}-1H-pyr-role-2-carbonitrile(DPPT) is also a progesterone receptor regulator.When lableled with99mTc, it might be useful for Single-Photon Emission Computed Tomography (SPECT)imaging of PR-positive breast tumors.In this study, we choose1-(2-amino-5-bromophenyl)ethanone, Borane-tetrahydrofuran,Methanesulfonyl chloride and2,2’-Dipicolylamine as raw material to prepare Tanaprogetanalogue DPPT by eight steps of reaction: Grignard reaction, CDI condensation, Suzukicoupling reaction of pyrrole-boric acid, cyano substitution, hydroboration-oxidation,mesylation, aminolysis, removal of the BOC.Important intermediate and target compoundshave been confirmed IR infrared spectrum, nuclear magnetic resonance (NMR), MS andelemental analysis for structure confirmation.The novel Tanaproget analogue DPPT was labeled with Tricarbonyl technetium toprepare99mTc(CO)3-DPPT. The factors which influence the RCP, such as the amount ofligand and99mTcO4-, pH value, were investigated to preparation of99mTc(CO)3-DPPT.The best conditions are as follows: the dosage of99mTcO4-is4mCi, pH is between2-4and dosage of ligands is4mg.Under optimization conditions, the radiochemical purity wasover95%and the lable complex was stable at least up to6h in vitro.The biological study of partition coefficients, plasma protein binding ratios,pharmacokinetics and biodistribution study were started to assess the properties of99mTc(CO)3-DPPT. The results show that99mTc(CO)3–DPPT are hydrophilic and transportfaster in the blood. Quick clearance in soft tissues were obtained from their pharmacokineticsand biodistribution study. These results demonstrate that the drugs for breast cancer have acertain target and this radiolabeled tanaproget derivative may be considered as potential breastcancer imaging agents.