Zynaxis' longterm goal is commercialization of diagnostic and therapeutic products based on novel methods for tracking autologous cells in vivo. Phase I goals were synthesis and characterization of a lipophilic cell tracking reagent suitable for radioimaging in animal models. An iodinated cell tracking molecule (PKH95) was synthesized which exhibited excellent membrane binding stability, minimal effects on cell viability and function, and minimal in vivo dehalogenation. Phase II will test the use of radiolabeled cell tracking molecules to monitor immune cell trafficking to metastatic tumor sites. 123I, 131I, and 125I reagents will be evaluated.
Specific aims are: i) optimize radioiodination procedure, ii) determine maximum non-toxic dose of I-PKH95 for murine and human LAKs and TILs in vitro, and iii) compare kinetics of LAK and TIL trafficking to tumor in lung and soft tissue and identify optimal conditions for tumor imaging. Thus Phase II studies will provide well characterized imaging reagents for the biomedical research market and set the stage for development of analogs combining lipophilic linkers with chelators for nuclides used in clinical imaging (99mTc, 111In, Gd).