Bioluminescence Imaging Correlates with Tumor Serum Marker, Organ Weights, Histology, and Human DNA Levels during Treatment of Orthotopic Tumor Xenografts with Antibodies

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.