Physical measurement of
tumor volume reduction is the most commonly used approach to assess
tumor progression and treatment efficacy in mouse
tumor models. However, it is relatively insensitive, and often requires long treatment courses to achieve gross physical
tumor destruction. As alternatives, several non-invasive imaging methods such as bioluminescence imaging (BLI), fluorescence imaging (FLI) and positron emission tomography (PET) have been developed for more accurate measurement. As
tumors have elevated
glucose metabolism, 18F-fludeoxyglucose (18F-FDG) has become a sensitive PET imaging tracer for
cancer detection, diagnosis, and efficacy assessment by measuring alterations in
glucose metabolism. In particular, the ability of
18F-FDG imaging to detect
drug-induced effects on
tumor metabolism at a very early phase has dramatically improved the speed of decision-making regarding treatment efficacy. Here we demonstrated an approach with FLI that offers not only comparable performance to PET imaging, but also provides additional benefits, including ease of use, imaging throughput, probe stability, and the potential for multiplex imaging. In this report, we used
sorafenib, a
tyrosine kinase inhibitor clinically approved for
cancer therapy, for treatment of a mouse
tumor xenograft model. The
drug is known to block several key signaling pathways involved in
tumor metabolism. We first identified an appropriate
sorafenib dose, 40 mg/kg (daily on days 0-4 and 7-10), that retained ultimate therapeutic efficacy yet provided a 2-3 day window post-treatment for imaging early, subtle metabolic changes prior to gross
tumor regression. We then used
18F-FDG PET as the gold standard for assessing the effects of
sorafenib treatment on
tumor metabolism and compared this to results obtained by measurement of
tumor size,
tumor BLI, and
tumor FLI changes. PET imaging showed ~55-60% inhibition of
tumor uptake of
18F-FDG as early as days 2 and 3 post-treatment, without noticeable changes in
tumor size. For comparison, two FLI probes, BombesinRSense™ 680 (BRS-680) and
Transferrin-Vivo™ 750 (TfV-750), were assessed for their potential in metabolic imaging. Metabolically active
cancer cells are known to have elevated
bombesin and
transferrin receptor levels on the surface. In excellent agreement with PET imaging, the BRS-680 imaging showed 40% and 79% inhibition on days 2 and 3, respectively, and the TfV-750 imaging showed 65% inhibition on day 3. In both cases, no significant reduction in
tumor volume or BLI signal was observed during the first 3 days of treatment. These results suggest that metabolic FLI has potential preclinical application as an additional method for detecting
drug-induced metabolic changes in
tumors.