Ghost 12 - Can't lock volume because it contains the OS or has an active paging file?

I just bought myself a Seagate 2TB external USB harddisk, and tried to use Ghost 12 to backup the C:\ drive to it.
I got a:

-Error E0BB001B: Cannot lock volume \\?\Volume{aaaaaaaa-bbbb-cccc-dddd-eeeeeeeeeeee}\ because it contains the OS or has an active paging file.

I recall successfully using Ghost 12 to backup the C:\ drive to a second internal harddisk not too long ago.

Why the failure now?