Welcome gumtree,

an ISO image won't work in most cases. You should use CloneCD's native format and it depends on the used protection if you're able to create a working image. So I would sugggest find out the used protection using a protection scanner and use the search function for example with the game title as keyword/s to take a look if this problem has already been discussed and a solution has been found. Good start is here and at first it all may look a bit complicated but in my opinion it's quite easy if you follow the instructions carefully, good luck.

p.s. PowerISO won't be much help here.