Assessing Antibody Pharmacokinetics in Mice with In Vivo Imaging

Abstract

Recent advances in small-animal molecular imaging instrumentation combined with well characterized antibody-labeling chemistry have enabled detailed in vivo measurements of antibody distribution in mouse models. This article reviews the strengths and limitations of in vivo antibody imaging methods with a focus on positron emission tomography and singlephoton emission computed tomography and a brief discussion of the role of optical imaging in this application. A description of the basic principles behind the imaging techniques is provided along with a discussion of radiolabeling methods relevant to antibodies. Practical considerations of study design and execution are presented through a discussion of sensitivity and resolution tradeoffs for these techniques as defined by modality, signaling probe (isotope or fluorophore) selection, labeling method, and radiation dosimetry. Images and analysis results from a case study are presented with a discussion of output data content and relevant informatics gained with this approach to studying antibody pharmacokinetics.

Effect of Small-Molecule–Binding Affinity on Tumor Uptake In Vivo: A Systematic Study Using a Pretargeted Bispecific Antibody

“…Some signal is also observed in the antigen-negative tumors, as expected from the biodistribution data. It should be noted that while 111 In and 177 Lu have similar reconstructed resolutions, the average sensitivity of 111 In is about five times greater than 177 Lu in mice (24). …”

In VivoFluorescence Imaging of the Activity of CEA TCB, a Novel T-Cell Bispecific Antibody, Reveals Highly Specific Tumor Targeting and Fast Induction of T-Cell–Mediated Tumor Killing

“…Whole-body fluorescence reflectance imaging allows noninvasive and longitudinal assessment of drug biodistribution as well as pharmacokinetic profiles with high sensitivity and temporal resolution in a cost-efficient manner (15)(16)(17). Complementing macroscopic imaging, intravital multiphoton microscopy has to-date become an important tool for the study the in vivo mode of action of therapeutic molecules such as antibodies at cellular and subcellular resolution within the tissue physiologic context (18).…”

A high throughput capillary electrophoresis method to obtain pharmacokinetics and quality attributes of a therapeutic molecule in circulation

“…Small animal body optical imaging using fluorescent probes for either ex vivo studies of isolated organs or whole body in vivo studies to evaluate distribution is a popular tool in pre-clinical work. 5,17 Many of the fluorophores used in these studies emit in the near infrared spectrum as tissue absorption and auto fluorescence are reduced at these wavelengths. 5 Using the GXII we now present the possibility of also collecting physicochemical characteristics and concentration in serum of the molecules being studied; thereby, expanding the amount of information collected from a single study.…”

“…5,17 Many of the fluorophores used in these studies emit in the near infrared spectrum as tissue absorption and auto fluorescence are reduced at these wavelengths. 5 Using the GXII we now present the possibility of also collecting physicochemical characteristics and concentration in serum of the molecules being studied; thereby, expanding the amount of information collected from a single study. The research and development of new fluorochromes that provide exquisite spatial resolution of molecules in vivo, as well as the burgeoning of microfluidic devices enabling high throughput analysis of various attributes of the molecule, herald promise in meeting the challenges of quickly bringing well-characterized drugs into the market.…”