Quantitative Distribution Studies in Animals: Cross-Validation of Radioluminography versus Liquid-Scintillation Measurement

Steinke, Wolfram; Archimbaud, Yves; Becka, Michael; Binder, Rudolf; Busch, Ulrich; Dupont, Patrick; Maas, Jochen

doi:10.1006/rtph.2000.1384

Cited by 30 publications

(13 citation statements)

References 7 publications

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“…The MicroComputer Imaging Device (MCiD Analysis, version 7; Imaging Research Inc., ON, Canada) was used to quantify the concentrations of radioactivity in the calibration standards and tissues of whole-body sections, as described by Potchoiba et al (1995) for 14 C xenobiotics. The quantitation method described here was demonstrated to be as accurate and precise as the values obtained from gamma or liquid scintillation counter methods (Potchoiba et al, 1995(Potchoiba et al, , 1998Busch et al, 2000;Steinke et al, 2000). The lower limit of quantification was determined by the lower detected concentration in the calibration standards (0.01 Ci/ml).…”

Section: Methodsmentioning

confidence: 70%

Effect of Immune Complex Formation on the Distribution of a Novel Antibody to the Ovarian Tumor Antigen CA125

Pastuskovas¹,

Mallet²,

Clark³

et al. 2010

Drug Metab Dispos

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ABSTRACT:3A5 is a novel antibody that binds repeated epitopes within CA125, an ovarian tumor antigen that is shed into the circulation. Binding to shed antigen may limit the effectiveness of therapeutic antibodies because of unproductive immune complex (IC) formation and/or altered antibody distribution. To evaluate this possibility, we characterized the impact of shed CA125 on the in vivo distribution of 3A5. In vitro, 3A5 and CA125 were found to form ICs in a concentration-dependent manner. This phenomenon was then evaluated in vivo using quantitative whole-body autoradiography to assess the tissue distribution of 125 I-3A5 in an orthotopic OVCAR-3 tumor mouse model at different stages of tumor burden. Low doses of 3A5 (75 g/kg) and pathophysiological levels of shed CA125 led to the formation of ICs in vivo that were rapidly distributed to the liver. Under these conditions, increased clearance of 3A5 from normal tissues was observed in mice bearing CA125-expressing tumors. Of importance, despite IC formation, 3A5 uptake by tumors was sustained over time. At a therapeutically relevant dose of 3A5 (3.5 mg/kg), IC formation was undetectable and distribution to normal tissues followed that of blood. In contrast, increased levels of radioactivity were observed in the tumors. These data demonstrate that CA125 and 3A5 do form ICs in vivo and that the liver is involved in their uptake. However, at therapeutic doses of 3A5 and clinically relevant CA125 levels, IC formation consumes only a minor fraction of 3A5, and tumor targeting seems to be unaffected.

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Section: Methodsmentioning

confidence: 70%

Effect of Immune Complex Formation on the Distribution of a Novel Antibody to the Ovarian Tumor Antigen CA125

Pastuskovas¹,

Mallet²,

Clark³

et al. 2010

Drug Metab Dispos

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“…Sample preparation is of key importance particularly con- (Adapted with permission from Ref. 19) cerning the choice of matrix and application method with regard to the ultimate crystal size, which may become the limiting step for high spatial resolution imaging analysis. It is important to note that, for ME-SIMS, the ion yields will be determined by the matrix application process (i.e., tissue extraction and cocrystallization), and thus, there is a significant loss of surface specificity in relation to the regular "surface sputtering" SIMS.…”

Section: Sample Optimizationmentioning

confidence: 99%

Autoradiography, MALDI-MS, and SIMS-MS Imaging in Pharmaceutical Discovery and Development

Solon¹,

Schweitzer

Stoeckli

et al. 2009

AAPS J

230

203

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Abstract. Whole-body autoradiography ((WBA) or quantitative WBA (QWBA)), microautoradiography (MARG), matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI), and secondary ion mass spectrometric imaging (SIMS-MSI) are high-resolution, molecular imaging techniques used to study the tissue distribution of radiolabeled and nonlabeled compounds in ex vivo, in situ biological samples. WBA, which is the imaging of the whole-body of lab animals, and/or their organ systems; and MARG, which provides information on the localization of radioactivity in histological preparations and at the cellular level, are used to support drug discovery and development efforts. These studies enable the conduct of human radiolabeled metabolite studies and have provided pharmaceutical scientists with a high resolution and quantitative method of accessing tissue distribution. MALDI-MSI is a mass spectrometric imaging technique capable of label-free and simultaneous determination of the identity and distribution of xenobiotics and their metabolites as well as endogenous substances in biological samples. This makes it an interesting extension to WBA and MARG, eliminating the need for radiochemistry and providing molecular specific information. SIMS-MSI offers a complementary method to MALDI-MSI for the acquisition of images with higher spatial resolution directly from biological specimens. Although traditionally used for the analysis of surface films and polymers, SIMS has been used successfully for the study of biological tissues and cell types, thus enabling the acquisition of images at submicrometer resolution with a minimum of samples preparation.

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“…This means that less than 25% of the initial 50 keV electrons are able to cross the protective layers. However, self-absorption Steinke et al, 2000) of the material on which the isotopes were spotted will also limit the transmission of these low energy electrons. In our experiments we used silica gel coated TLC plates (thickness of silica gel layer: 250 m).…”

Section: Properties Of the Tested Radioisotopesmentioning

confidence: 97%

In vitro and ex vivo storage phosphor imaging of short-living radioisotopes

Knol

Bruin

Jong

et al. 2008

Journal of Neuroscience Methods

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Quantitative Distribution Studies in Animals: Cross-Validation of Radioluminography versus Liquid-Scintillation Measurement

Cited by 30 publications

References 7 publications

Effect of Immune Complex Formation on the Distribution of a Novel Antibody to the Ovarian Tumor Antigen CA125

Effect of Immune Complex Formation on the Distribution of a Novel Antibody to the Ovarian Tumor Antigen CA125

Autoradiography, MALDI-MS, and SIMS-MS Imaging in Pharmaceutical Discovery and Development

In vitro and ex vivo storage phosphor imaging of short-living radioisotopes

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