Positron Emission Tomography Imaging Of Cell Death And Tumor With Various Radiolabeled Tracers

Duramycin binds specifically to phosphatidylethanolamine (PE), a novelmolecular target for cell death. N-(2-18F-Fluoropropionyl)duramycin([18F]FPDuramycin) was prepared as a novel positron emission tomography (PET)tracer from the reaction of duramycin with4-nitrophenyl2-[18F]fluoropropionate([18F]NFP). The overall uncorrected radiochemical yield of [18F]FPDuramycin was10±5.0%(n=8) from18F-. And the total synthesis time was120min. The specificactivity was greater than23.7±13.7GBq/μmol (n=8). Compared with control cells(viable tumor cells), the in vitro binding of [18F]FPDuramycin with apoptotic cellsinduced by anti-Fas antibody resulted in a doubling increase, while the binding of[18F]FPDuramycin with necrotic cells induced by three freeze and thaw cyclesresulted in a threefold increase. Biodistribution study in mice exhibited its rapid bloodand renal clearance and predominant accumulation in liver and spleen over120minpostinjection. Small-animal PET/CT imaging with [18F]FPDuramycin proved to be asuccessful method to visualize in vivo therapeutic-induced tumor cell death. Insummary,[18F]FPDuramycin could be a potential PET probe candidate fornoninvasive visualization of in vivo cell death sites induced by chemotherapy intumors. We have synthesized precursors of [18F]ML-8(analogues to ML-10) and[18F]-DFESB, and finished the radiolabeling procedure and the bioevaluation studies.For the tumor imaging studies, we have previously reported that N-(2-[18F]fluoropropionyl)-L-methionine ([18F]FPMET) selectively accumulates in tumors.However, due to the poor pharmacokinetics of [18F]FPMET in vivo, the potentialclinical application of this observation is difficult. Therefore, we designed andsynthesized [18F] or [11C]labeled N-position L-glutamic acid analogues for tumorimaging. N-(2-[18F]fluoropropionyl)-L-glutamic acid ([18F]FPGLU) was synthesizedwith a30±10%(n=10, decay-corrected) overall radiochemical yield and a specificactivity of40±25GBq/μmol (n=10) after130min of radiosynthesis. In vitro cellexperiments showed that [18F]FPGLU was primarily transported through the XAG–system and was not incorporated into protein.[18F]FPGLU was stable in urine, tumortissues and blood. We were able to use [18F]FPGLU in PET imaging and obtainedhigh tumor to background ratios when visualizing tumors tissues in animal models. In addition, we have accomplished some preliminary evaluations of [18F]FPWAVGHLMand [18F]FPArg as tumor imaging PET tracers.In addition, we have presented synthetic works, epi-Estriol is the precursor of[18F]FES (a PET tracer used for the detection of mammary cancer).