New SPECT imaging agents for the translocator protein

A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the Author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the Author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. Abstract During the course of the studies outlined in this thesis, a new short and efficient synthesis of PK11195 was developed using Pd(0)-mediated reactions to effect the key carbon-carbon bond forming reactions. PK11195 is a ligand that interacts with the translocator protein (TSPO) in the brain. During brain injury the concentration of TSPO increases, making TSPO an ideal and sensitive biomarker. Using single photon emission computed tomography along with [ 123 I]PK11195, medical practitioners are able to visualize the receptor. In addition to the synthesis of PK11195, three other analogues were devised using the same methodology as for PK11195. Firstly, a Heck reaction was used to form the isoquinoline core, followed by a Suzuki reaction to couple the correct phenyl ring.