A spokesperson representing Madeleine's parents Kate and Gerry told the Mirror: "The letter is a significant development. It is necessary for British police to request the Portuguese authorities allow them to operate on their turf.
"It means they have the intention of arresting and interviewing X, Y or Z. We don't know who they have their sights on but it's likely it is the burglars.
"Whether the Portuguese will co-operate remains to be seen. It is a very sensitive issue with differences they have had."
The spokesperson added that while it could be a "significant new lead", Kate and Gerry did not want to build their hopes up too high.
The CPS sent the international letter of request last week, BBC News reported. The last time it did so was in July, when British police said they were investigating 38 "persons of interest" and that a review had been upgraded into a formal investigation.
The search for Madeleine, who police say could still be alive, was given new impetus in November with an episode of the BBC's Crimewatch programme.
Then, Detective Chief Inspector Andy Redwood, a senior detective investigating the disappearance, said several holidaymakers who were in Praia da Luz at the time had made contact with his team.
Mr Redwood said: "The media appeals produced a fantastic response from the public in all three countries with a total of 3500 calls and messages in the UK, 850 to Germany, and 650 in Holland."
- Independent