Method for forming cationic technetium complexes useful as radiodiagnostic agents

Claim 1

A method for preparing cationic lipophilic technetium complexes for radiodagnostic imaging, said method comprising (1) admising 99m Tc-pertechnetate with a target-seeking ligand or aqueous salt thereof, said ligand having the following structure: ##STR9## wherein: i is an integer from 1 to 6; R, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are each independently selected from hydrogen or substituted or unsubstituted alkyl, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups, and R plus R i may be taken together to form a cyclic compound or separately to form a linear compound; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 are independently selected from hydrogen or substituted or unsubstituted alkyl, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; A 1 , A 2 , A 3 , A 4 , A 5 and A 6 are each, independently, a donor atom having a free-electron pair available for complexing with Tc-99m or Tc-99 to form a cationic complex; and k 1 , k 2 , k 3 , k 4 , k 5 and k 6 are each independently zero or one; or ##STR10## wherein: R, R' and R" are independently selected from hydrogen or substituted or unsubstituted alkyl, aryl, alkylaryl, arylalkyl, monocylcloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; X and X' are saturated or unsaturated alkyl groups; A, A' and A" are independently selected from the group of donor atoms having a pair of electrons available for complexing with Tc-99m or Tc-99 to form a cationic complex; t and t' are independently 0 or 1; n is 0, 1 or 2; and n' and n" are independently the integer 1 or 2; or ##STR11## wherein R, R', R" and R'" are independently selected from hydrogen or substituted or unsubstituted alkyl, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; A', A" and A'" are independently selected from the group of donor atoms having a pair of electrons available for complexing with Tc-99m or Tc-99 to form a cationic complex; B is an atom from the group of donor atoms having a pair of electrons available for complexing with Tc-99m or Tc-99, boron, or from the elements of Group IV A of the periodic table; m is 0 or 1; and n, n', n" and n'" are independently the integer 1 or 2; and (2) heating the admixture to a temperature greater than 100° C. for a suitable length of time to complete the labelling reaction.

Claim 2

A method for preparing cationic lipophilic technetium complexes for radiodagnostic imaging, said method comprising (1) admising 99m Tc-pertechnetate with a target-seeking ligand or aqueous salt thereof, said ligand having the following structure: ##STR9## wherein: i is an integer from 1 to 6; R, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are each independently selected from hydrogen or substituted or unsubstituted alkyl, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups, and R plus R i may be taken together to form a cyclic compound or separately to form a linear compound; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 are independently selected from hydrogen or substituted or unsubstituted alkyl, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; A 1 , A 2 , A 3 , A 4 , A 5 and A 6 are each, independently, a donor atom having a free-electron pair available for complexing with Tc-99m or Tc-99 to form a cationic complex; and k 1 , k 2 , k 3 , k 4 , k 5 and k 6 are each independently zero or one; or ##STR10## wherein: R, R' and R" are independently selected from hydrogen or substituted or unsubstituted alkyl, aryl, alkylaryl, arylalkyl, monocylcloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; X and X' are saturated or unsaturated alkyl groups; A, A' and A" are independently selected from the group of donor atoms having a pair of electrons available for complexing with Tc-99m or Tc-99 to form a cationic complex; t and t' are independently 0 or 1; n is 0, 1 or 2; and n' and n" are independently the integer 1 or 2; or ##STR11## wherein R, R', R" and R'" are independently selected from hydrogen or substituted or unsubstituted alkyl, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; A', A" and A'" are independently selected from the group of donor atoms having a pair of electrons available for complexing with Tc-99m or Tc-99 to form a cationic complex; B is an atom from the group of donor atoms having a pair of electrons available for complexing with Tc-99m or Tc-99, boron, or from the elements of Group IV A of the periodic table; m is 0 or 1; and n, n', n" and n'" are independently the integer 1 or 2; and (2) heating the admixture to a temperature greater than 100° C. for a suitable length of time to complete the labelling reaction.