Can of Compressed air,or remove fan first and have a look at heatsink fins. You can always remove it completely and give it an overhaul,although you would then have to clean heatsink and reapply thermal goo
On the couple of occasions I've needed to clean out my tower unit I've removed the side panel, laid the tower on it's side so the motherboard is at the bottom then used a selection of soft to firm brushes. [Wrap insulation tape around the metal part of the brush].
Use compressed air to remove the fluff from the CPU heatsink fins, then stand the tower unit back up the correct way and use a plastic nozzle on the end of a vacuum cleaner hose to remove all the fluff that is now sitting on the base of the case.
Remember to not only turn off the PC but to unplug from the socket as well. Modern motherboards still have a trickle feed to them even though turned off. This is a good point to remember if your inserting/removing any memory sticks or PCI cards as the board could cause a short if you touch the wrong part while it's live.
Thats fine as I explain in my post above but just for removing all the fluff and dust that you have dislodged and is now on the base of the case.
The only problem with using a vacuum cleaner is the power of suction and the plastic nozzle itself may move or even damage some of the extremely delicate parts on the board. By all means use as you suggest but with care. j.