Dataset Information

Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo.

ABSTRACT: The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model to estimate the density of receptors available for binding in the tissue. Applying this approach to mice with deep-seated gliomas that overexpress the EGF receptor produced an estimate of available receptor density of 2.3 ± 0.5 nM (n = 5), consistent with values estimated in comparative invasive imaging and ex vivo studies.

SUBMITTER: Davis SC

PROVIDER: S-EPMC3670304 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo.

Davis Scott C SC Samkoe Kimberley S KS Tichauer Kenneth M KM Sexton Kristian J KJ Gunn Jason R JR Deharvengt Sophie J SJ Hasan Tayyaba T Pogue Brian W BW

Proceedings of the National Academy of Sciences of the United States of America 20130513 22

The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent t ...[more]

PMID: 23671066

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Project description:Pulmonary perfusion with dynamic contrast-enhanced (DCE-) MRI is typically assessed using a single-input tracer kinetic model. Preliminary studies based on perfusion CT are indicating that dual-input perfusion modeling of lung tumors may be clinically valuable as lung tumors have a dual blood supply from the pulmonary and aortic system. This study aimed to investigate the feasibility of fitting dual-input tracer kinetic models to DCE-MRI datasets of thoracic malignancies, including malignant pleural mesothelioma (MPM) and nonsmall cell lung cancer (NSCLC), by comparing them to single-input (pulmonary or systemic arterial input) tracer kinetic models for the voxel-level analysis within the tumor with respect to goodness-of-fit statistics. Fifteen patients (five MPM, ten NSCLC) underwent DCE-MRI prior to radiotherapy. DCE-MRI data were analyzed using five different single- or dual-input tracer kinetic models: Tofts-Kety (TK), extended TK (ETK), two compartment exchange (2CX), adiabatic approximation to the tissue homogeneity (AATH) and distributed parameter (DP) models. The pulmonary blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), fractional interstitial volume (vI ), and volume transfer constant (KTrans ) were calculated for both single- and dual-input models. The pulmonary arterial flow fraction (?), pulmonary arterial blood flow (BFPA ) and systemic arterial blood flow (BFA ) were additionally calculated for only dual-input models. The competing models were ranked and their Akaike weights were calculated for each voxel according to corrected Akaike information criterion (cAIC). The optimal model was chosen based on the lowest cAIC value. In both types of tumors, all five dual-input models yielded lower cAIC values than their corresponding single-input models. The 2CX model was the best-fitted model and most optimal in describing tracer kinetic behavior to assess microvascular properties in both MPM and NSCLC. The dual-input 2CX-model-derived BFA was the most significant parameter in differentiating adenocarcinoma from squamous cell carcinoma histology for NSCLC patients.

Dataset Information

Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo.

Publications

Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo.

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