The emergence of argon - based gas cluster ion beams for SIMS experiments opens new possibilities for molecular depth profiling and 3D chemical imaging. These beams generally leave less surface chemical damage and yield mass spectra with reduced fragmentation when compared to smaller cluster projectiles. For nanoscale bioimaging applications, however, limited sensitivity due to low ionization probability and technical challenges of beam focusing remain problematic. The use of gas cluster ion beams based upon systems other than argon offer an opportunity to resolve these difficulties. Here we report on the prospects of employing CO2 as a simple alternative to argon. Ionization efficiency, chemical damage, sputter rate and beam focus are investigated on model compounds using a series of CO2 and Ar cluster projectiles (cluster size 1000~5000) with the same mass. The results show that the two projectiles are very similar in each of these aspects. Computer simulations comparing the impact of Ar2000 and (CO2)2000 on an organic target also confirm that the CO2 molecules in the cluster projectile remain intact, acting as a single particle of m/z 44. The imaging resolution employing CO2 cluster projectiles is improved by more than a factor of 2. The advantage of CO2 vs Ar is also related to the increased stability which, in addition, facilitates the operation of the GCIB system at lower backing pressure.