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Purpose: Pharmacokinetic modeling can be applied to quantify the kinetics of fluorescently labeled compounds using longitudinal micro-computed tomography and fluorescence-mediated tomography (μCT-FMT). However, fluorescence blurring from neighboring organs or tissues and the vasculature within tissues impede the accuracy in the estimation of kinetic parameters. Contributions of elimination and retention activities of fluorescent probes inside the kidneys and liver can be hard to distinguish by a kinetic model. This study proposes a deconvolution approach using a mixing matrix to model fluorescence contributions to improve whole-body pharmacokinetic modeling. Procedures: In the kinetic model, a mixing matrix was applied to unmix the fluorescence blurring from neighboring tissues and blood vessels and unmix the fluorescence contributions of elimination and retention in the kidney and liver compartments. Accordingly, the kinetic parameters of the hepatobiliary and renal elimination routes and five major retention sites (the kidneys, liver, bone, spleen, and lung) were investigated in simulations and in an in vivo study. In the latter, the pharmacokinetics of four fluorescently labeled compounds (indocyanine green (ICG), HITC-iodide-microbubbles (MB), Cy7-nanogels (NG), and OsteoSense 750 EX (OS)) were evaluated in BALB/c nude mice. Results: In the simulations, the corrected modeling resulted in lower relative errors and stronger linear relationships (slopes close to 1) between the estimated and simulated parameters, compared to the uncorrected modeling. For the in vivo study, MB and NG showed significantly higher hepatic retention rates (P<0.05 and P<0.05, respectively), while OS had smaller renal and hepatic retention rates (P<0.01 and P<0.01, respectively). Additionally, the bone retention rate of OS was significantly higher (P<0.01). Conclusions: The mixing matrix correction improves pharmacokinetic modeling and thus enables a more accurate assessment of the biodistribution of fluorescently labeled pharmaceuticals by μCT-FMT. [ABSTRACT FROM AUTHOR]

The process of angiogenesis, an essential hallmark for tumour development as well as for several inflammatory diseases and physiological phenomena, is of growing interest for diagnosis and therapy in oncology. In the context of biochemical characterisation of key molecules involved in angiogenesis, several targets for imaging and therapy could be identified in the last decade. Optical imaging (OI) relies on the visualisation of near infrared (NIR) light, either its absorption and scattering in tissue (non-enhanced OI) or using fluorescent contrast agents. OI offers excellent signal to noise ratios due to virtually absent background fluorescence in the NIR range and is thus a versatile tool to image specific molecular target structures in vivo. This work intends to provide a survey of the different approaches to imaging of angiogenesis using OI methods in preclinical research as well as first clinical trials. Different imaging modalities as well as various optical contrast agents are briefly discussed. [ABSTRACT FROM AUTHOR]

Optical imaging would be desirable for cancer diagnostics since it can potentially resolve relevant oncological target structures in vivo. We therefore synthesised an αvβ3 targeted fluorochrome and imaged tumour xenografts with different αvβ3 expression levels using both planar and tomographic optical imaging methods. An αvβ3-targeted RGD peptide was labelled with a cyanine dye (Cy 5.5). Binding of the optical tracer was tested on M21 melanoma ( n = 5), HT-1080 fibrosarcoma ( n = 6) and MCF-7 adenocarcinoma ( n = 5) cells and their tumour xenografts. All optical imaging studies were performed using two-dimensional planar fluorescence reflectance imaging (FRI) technology and three-dimensional fluorescence-mediated tomography (FMT). In vitro, the peptide-dye conjugate showed a clear binding affinity to αvβ3-positive M21 and HT-1080 cells while αvβ3-negative MCF-7 cells and pre-dosing with the free RGD peptide revealed little to no fluorescence. In vivo, tumour xenografts were clearly visualised by FRI and FMT up to 24 h post injection. FMT allowed quantification of the fluorochrome distribution in deeper tissue sections showing an average fluorochrome concentration of 417.61 ± 105.82 n M Cy 5.5 (M21), 353.68 ± 54.02 n M Cy 5.5 (HT-1080) and 262.83 ± 155.36 n M Cy 5.5 (MCF-7) in the target tissue 60 min after tracer administration. Competition with the free RGD peptide resulted in a reduction in the fluorochrome concentration in M21 tumour tissue (294.35 ± 84.27 n M). RGD-Cy 5.5 combined with novel tomographic optical imaging methods allows non-invasive imaging of tumour-associated αvβ3 expression and may thus be a promising strategy for sensitive evaluation of tumour target expression. [ABSTRACT FROM AUTHOR]