Key result
Noninvasive optical bioluminescence tracking strongly correlates with cardiac gene expression in living rats.
Why the study?
Studies of cardiac gene transfer rely on postmortem analysis, and noninvasive imaging of cardiac gene expression in living subjects offers significant advantages.
This study demonstrates the feasibility of noninvasively imaging the location, magnitude, and time course of cardiac reporter gene expression in living rats using a cooled CCD camera.
Answers are grounded in this paper and cite their sources.
Optical imaging enables noninvasive cardiac gene expression tracking in rats; extends preclinical tools but leaves open clinical translation.
BACKGROUND: Studies of cardiac gene transfer rely on postmortem analysis using histologic staining or enzyme assays. Noninvasive imaging of the temporal and spatial characteristics of cardiac gene expression in the same subject offers significant advantages. METHODS AND RESULTS: Rats underwent direct myocardial injection via left thoracotomy with adenovirus-expressing firefly luciferase (Ad-CMV-Fluc; n=30). The reporter substrate D-luciferin was injected intraperitoneally. Serial images were acquired by use of a cooled charged couple detector (CCD) camera. Results are expressed as relative light unit per minute (RLU/min). Rats transduced with 1x10(9) plaque-forming units show decremental cardiac luciferase activity over time: 152 070+/-21 170 (day 2), 195 806+/-62 630 (day 5), 7250+/-2941 (day 8), and 2040+/-971 RLU/min (day 14). To assess the detection sensitivity, serially diluted titers of Ad-CMV-Fluc were injected: 1x10(9) (195 393+/-14 896), 1x10(8) (33 777+/-18 179), 1x10(7) (417+/-91), 1x10(6) (185+/-64), 1x10(5) (53+/-1), and control (54+/-1) (P<0.05 for 1x10(9), 1x10(8), and 1x10(7) plaque-forming units versus control adenovirus-expressing mutant thymidine kinase [Ad-CMV-HSV1-sr39tk]; n=3). Finally, rats were euthanized, and in vitro luciferase activity correlated with in vivo CCD signals (r2=0.92). CONCLUSIONS: This study demonstrates for the first time the feasibility of imaging the location, magnitude, and time course of cardiac reporter gene expression in living rats. Cardiac gene therapy studies could be aided with wider application of this approach.
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Wu et al. (2002) studied Cardiac gene transfer (n=33). Adenovirus-expressing firefly luciferase (Ad-CMV-Fluc) vs. Adenovirus-expressing mutant thymidine kinase (Ad-CMV-HSV1-sr39tk) was evaluated on Cardiac luciferase activity (RLU/min) (p=<0.05). Noninvasive optical imaging successfully detected cardiac reporter gene expression in living rats, with in vivo signals strongly correlating with in vitro luciferase activity (r2=0.92).
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