Positron Emission Tomography (PET) offers the uniqueness of non-invasive in vivo quantification for a variety of biological diseases. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) has shown great promises to be a powerful unique clinical tool for the diagnosis and the staging of many carcinomas, especially when it is used simultaneously with Computed Tomography (CT). Nonetheless, the validity of FDG as a radiotracer for glucose metabolism in cancer cells is still not well understood. In order to explore this further, four human non-small cell lung cancer (NSCLC) lines (squamous, adenocarcinoma, large cell, and bronchioalveolar) will be immobilized with microcarriers in suspension. This 3-D tissue culture system where cells are isolated from other control factors is analogous to an isolated perfused heart system. Time activity curves (TAC) will be obtained in high temporal resolution by on-line dynamic measurement of FDG uptake into cells with two external gamma probes. The TAC will be further analyzed by a compartmental model for kinetic parameters associated with both the transport and phosphorylation steps.
Three specific aims for this proposal are: 1. To determine the growth conditions to obtain a steady state of immobilized cells per gram microcarrier for four common types of NSCLCs, 2. To characterize the metabolic and hemodynamic parameters (oxygen, glucose, lactate, CO2, pH, temperature) for all four cell types in the 3-D tissue culture system, 3. To investigate FDG kinetics and the lumped constant behaviour in all four cell types. Since the overexpression of glucose transporter and hexokinase isoforms are not expected to be the same for all carcinomas, FDG kinetics in these four NSCLCs should demonstrate certain degree of differential uptakes. Results obtained from the proposed research will provide a basis for the understanding of FDG kinetics in cancer cells and the identification of new non-invasive means to probe biological diseases. The same experimental setup can also be used with many other types of cells to probe biological diseases with either PET or SPECT ligands. FDG kinetics in NSCLCs was chosen only to demonstrate its potential utility by relating problems to a well-established clinical procedure in PET imaging. Therefore the long-term objective is to develop a versatile experimental setup that combines a 3-D tissue culture system with external gamma probes for the development and the evaluation of radiopharmaceuticals.
