Synthesis Of Znic-dipicolylamines As New Positron Emission Tomography Imaging Agents For Apoptosis

Positron emission computed tomography （PET） is an imaging technique that canshow the metabolism of biological molecule, the activity of receptor andneurotransmitter. PET demonstrates the capability to obtain the three-dimendionalimage with best sensitivity and resolution among the nuclear medicine imagingmodalities. The half life of¹⁸F isotope is110min, which is longer than the otherclinieally used nuclides such as¹¹C,¹⁵O and¹³N. Therefore, it allows the preparationof complieated radiotracers labeled with¹⁸F isotop.A series of zinc （II） dipicolylamine (Zn²⁺-DPA) coordination compounds has beendeveloped that can report the presence of phosphatidylserine in the outer leaflet of acell membrane. Based on the previous methods for detection of apoptosis, weproposed to design a series of PET imaging agents for apoptosis and the workinvoloves the synthesis of [¹⁸F] FEDPA and [¹⁸F] EGDPA.The synthesis of [¹⁸F] FEDPA was departed in four parts:1. We first chose Pd on charcoal as catalyst, and the2-cyanopyridine was treatedwith hydrogen under pressure20atm to get the di（2-picolyl）amine.2. Commercially available5-hydroxy-isophthalic acid was conversed to diesterby esterification and subsequent reduction with lithium aluminium hydride （LAH）produced3,5-bishydroxy-methyl-phenol.3. Conversion of the triethylene glycol to the intermediate17by nucleophilicsubstitution, reduction and esterification.4.3,5-bishydroxy-methyl-phenol, di（2-picolyl）amine and compound10wereused to synthesize precursor. Then [¹⁸F] FEDPA was radiosynthesized.On the basis of the successful experience with the previous work of [¹⁸F] FEDPA,we expand this [¹⁸F] EGDPA to develop high performance imaging probes.All compounds presented in this work have either immediate applications indiagnostic imaging or the potential to help us understand more about the process ofmolecular recognition in a cell membrane interior.