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I would think so. You would have to mess with things like the engine mounts and stuff. But a lot of the work is going to depend on the transmission and transfer case.
wouldnt you need to beef up the springs? not a real expert (but learning !) isnt the 460 a bit heavier then lets say a 351? though a 400m is pretty heavy...
A set of conversion motor mounts, the oil filter relocation kit or as some have suggested, notch the crossmember at the oil filter point (it should only interfere a little), make sure you get a transmission that bolts to the 460 (351M, 400M, 429, 460 all work). The 460 weighs about 200lbs more than a 351W, it's like 720-725 lbs vs. 525ish. If it's four wheel drive, that can become a whole new ball game. I'm just finishing up a 460 swap in a 250 4x4, and I have to get both driveshafts made for it. You may also need to swap the oil pan and pickup/screen to a rear sump on the 460 if yours is 4x4, not sure if that would be the case on a 2x4. If you pick up a 460 with a front sump pan and pickup, anyways.
one of my friends did this swap. i sold him an 85 F250 2wd with a 460. he got the c6 behind the 460 made into a 4x4 tranny with the parts from his windsor c6. the oil pan cleared, its already a rear sum. the oil filter on the 85 truck is indexable so to speak... you can roll it if you know what i'm saying.. it pivots on a bolt and its at about a 30 or so degree angle. so you can turn it into a position that works for you...he did have to do a lot of double checking on that one to make sure it wouldnt hit. used the rad out of the f250. but it was all basically straight forward.. just tedious. helps if you have a donor truck like that for misc. parts. or an engine with everything from one of those.. but a filter relocation kit would work perfect too...maybe even a little easier. the 85 f250 also had an engine oil cooler.. so it had an extra block inbetween the engine and filter with fittings in it. i dont think he used it though.