Santa Cruz, who is currently on loan at Malaga, only managed 24 appearances in all competitions for City since joining from Blackburn Rovers in 2009.
The Paraguayan has since had a loan spell back at Ewood Park as well as a season with Real Betis, but Brazil looks to be his next destination, according to his agent Robson Lima.
"Talks were very good, Botafogo are a very serious club. The player is excited about the possibility," Lima told Lancenet.
"We are negotiating with Botafogo but we can't say if the deal will work out in the end."