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Because of the way that DropBox works this is not technically possible. There is no feature in DropBox that informs the local app that the file in question is open elsewhere.
You could probably write your own crude check mechanism if you wrote a script/batch file (depending on OS) to check if a marker file that you created during the Calibre launch existed. However you would have to handle issues like making sure that the file was removed when Calibre cleanly exited; having an over-ride capability for case where Calibre crashed and also making sure that wherever you started Calibre you had an active internet connection so that DropBox could replicate the required file changes. Therefore whether it is worth it might be something to consider.
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