TY - JOUR T1 - Quantitative in vivo imaging of slowly diffusing radiotracers JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 48 LP - 48 VL - 54 IS - supplement 2 AU - Moses Wilks AU - Scott Knowles AU - Anna Wu AU - Sung-Cheng Huang Y1 - 2013/05/01 UR - http://jnm.snmjournals.org/content/54/supplement_2/48.abstract N2 - 48 Objectives Previous studies have shown disagreement between in vivo and in vitro measurements of kinetic parameters in large molecule tracers. For such tracers (like labeled antibodies), standard kinetic models fail sometimes to accurately measure tracer kinetics, necessitating models incorporating the diffusion rate of tracer in tissue. The reaction-diffusion equations central to these improved models are highly non-linear, leading to problems of parameter identifiability. Here we propose and implement a method to overcome these problems for in vivo imaging using Bayesian priors based on in vitro measurements. Methods Quartz crystal microbalance (QCM) experiments were performed on PSCA antigen to measure kon and koff of the of 124I-PSCA minibody (A11) in vitro. Mice implanted with PSCA over-expressing tumors were then injected with ~100 µCi A11 and scanned intermittently over 44 hours. ROIs were drawn on the left ventricle and the implanted tumor to measure plasma and tumor activity in each mouse. The tumor time activity curves (TAC) were then fit with both standard kinetic models and the diffusion-kinetic model with Bayesian priors. Results QCM experiments estimated Kd of A11 as ~4nM. With diffusion-kinetic models, TACs were fit with high accuracy and fitted parameters agreed closely with a priori estimates of binding affinities (estimated Kd ~ 2nM). TACs were also fit well using standard kinetic models, but showed large divergence from in vitro estimates of kon and koff , with a fitted Kd of ~10μM. There were also large differences in fitted parameters of receptor density, with estimated receptor density 300% larger when diffusion is not taken into account. Conclusions Using standard kinetic models for quantification of in vivo imaging with large molecule tracers leads to large errors in estimates of important biological parameters. These problems can be overcome by accounting for diffusion rate of tracer and incorporating some Bayesian priors. This method can be used to accurately measure changes in receptor density as a function of treatment response. ER -