As long as you're using the latest d2x cIOS and a loader that supports Block IOS Reload, there's no reason Metroid Prime Trilogy shouldn't work normally; you shouldn't have to use the alternate dol method. I recommend you use ModMii to install the latest and recommended cIOS files. I also recommend you use the latest version of
Configurable USB Loader MOD (my favorite) or another loader that supports Block IOS Reload. In Configurable USB Loader MOD, Block IOS Reload is enabled by default.
If the above doesn't fix your problem, then it's probably a bad file. There are versions of Metroid Prime Trilogy ISOs that are bad and won't allow one to load Metroid Prime 3 (and there are ones that intentionally have Metroid Prime 3 cut out). I recommend you try getting your backup from another source.
Out of curiosity, which game are you trying to play?