Different imaging modalities are being used to monitor disease progression and to analyze therapeutic efficacy in preclinical stages of drug development.
According to Werner Scheuer, Ph.D., group leader, preclinical optical imaging, pharmacology TR-PD, and pharmaceutical research at Roche Diagnostics, fluorescence and bioluminescence technologies are best because of their sheer simplicity, fast scanning times, nonhazardous radiation, and nonradioactive isotopes.
In pharmaceutical drug development, long acquisition times can hinder efforts to determine pharmacodynamics and pharmacokinetics in preclinical models. Speaking with GEN, Dr. Scheuer explained that optical imaging has very short acquisition times, ranging from one second to two minutes.
Using fluorescence-labeled antibodies targeting a tumor-associated surface antigen, accumulation in tumor tissue can be accomplished within six to 24 hours post-injection. As such, it is possible to monitor the biodistribution of the therapeutic antibodies in preclinical cancer xenografts. By using fluorophores that differ in their emission spectra, it is possible to examine a combination of antibodies. Such multiplexing studies cannot be performed using radioactive isotopes.
Further, in combination with luciferase-transfected tumor cells, it is possible to monitor binding kinetics and antitumoral efficacy noninvasively and simultaneously. Fluorescence-labeled antibodies are stable ranging from six to 12 months at -20°C, making them superior to radioactive isotopes. Furthermore, noninvasive fluorescence imaging in mice allows monitoring of blood peak levels, half-life, organ distribution and saturation kinetics. It improves the quality of data for pharmacokinetic and pharmacodynamic simulation. It also reduces the number of animals needed, reducing time and costs.
Combination of fluorescence with bioluminescence and subsequent examination of explanted organs by 3D multispectral fluorescence histology enables the monitoring of primary tumor growth, metastasis, and angiogenesis. Dr. Scheuer and his colleagues have demonstrated the advantages of optical imaging in the combined measurement of pharmacodynamics and pharmacokinetics in cancer xenografts.