Bioluminescence imaging correlates with tumor serum marker, organ weights, histology, and Human DNA levels during treatment of orthotopic tumor xenografts with antibodies

摘要

Purpose: In this study, we correlate results of bioluminescence measurements with established readouts for assessing therapeutic efficacy of antibodies in orthotopic cancer xenografts. Procedures: An orthotopic tumor model of pancreatic cancer (AsPC-1-luc) and experimental lung metastasis (A549-luc) were established. Whole-body bioluminescence imaging (BLI) was performed to observe tumor progression under therapy with antibodies targeting different receptor kinases (primary readout). For purpose of verification, anti-tumoral efficacy was cross-validated with results obtained by measurement of organ weights, histology, tumor serum marker analysis (CYFRA 21-1), and quantification of human DNA concentration in the organ of interest (secondary readouts). Results: Anti-tumoral efficacy is demonstrated for the antibodies tested. In the pancreas xenograft, a tumor growth inhibition of 95% (p < 0.01) was achieved as compared to control. Therapeutic efficacy could be identified as soon as 1 week after initiation of treatment. In the model of experimental lung metastasis, antibody treatment significantly suppressed tumor growth up to 75% (p < 0.05). All imaging results were confirmed by correlation analysis showing excellent agreement with the secondary readouts. Conclusions: BLI was demonstrated to be a reliable tool for monitoring early drug responses in orthotopic small animal cancer models. BLI allows rapid and non-invasive assessment of tumor load in the animal over time and, thus, provides a suitable method for routine use in preclinical cancer research. ? 2012 World Molecular Imaging Society.