British police have identified 38 potential suspects in the disappearance of Madeleine McCann.
London police have begun their own investigation after Madeleine went missing from her room at the Praia da Luz holiday resort in the Algarve on May 2007.
"We continue to believe that there is a possibility that Madeleine is alive," said Detective Chief Inspector Andy Redwood.
"It is a positive step in our hunt for Madeleine that our understanding of the evidence has enabled us to shift from review to investigation."
Despite massive international interest and numerous reported sightings from Belgium and Spain to Morocco, France and Malta, and investigations stretching as far away as Australia, the little girl's fate remains a mystery.
"We have identified 38 persons of interest from a number of European countries," Chief Insp Redwood said. "Twelve of those people are UK nationals who we believe were in Portugal at the time Madeleine disappeared."
Her parents were named as official suspects by Portuguese police four months after Madeleine's disappearance but in 2008 they were cleared and Portugal's public prosecutor later dropped the case, citing a lack of evidence.
London police launched a review of the case in 2011 after the couple wrote to British Prime Minister David Cameron saying not enough was being done to find their daughter.
Since then British detectives have made 16 trips to Portugal and pulled together thousands of documents collected from Britain, Portugal and private investigators from seven different companies who had worked on the case.
That had led to "in excess of 3,800 actions", yielding new findings and new evidence from witnesses, they said.
Officers from his team have now formally requested that Britain's Crown Prosecution Service submit a letter to the Portuguese authorities asking for help in obtaining evidence relating to potential leads.
"Kate and Gerry warmly welcome the shift in the Met's emphasis from review to investigation," the McCanns said in a statement to media.