Metal-binding targeted polypeptide constructs

A method of enhancing an MR image of an internal region of a subject comprising administering to a subject an effective amount of the complex of the formula (II):

• ##STR13## in which, "B" is a saturated or unsaturated aliphatic or aromatic hydrocarbon backbone comprising 1-20 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• "P" is a polypeptide comprising 2-200 amino, said polypeptide capable of targeting particular cells, tissues or organs of the body;
• "A" may be the group --NR'--NR'-- or the group --NR'--NR"--L-- in which L may be an aliphatic or aromatic linker group comprising 1-12 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• R, R', R" may be the same or different and may be hydrogen or an aliphatic group comprising 1-6 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• and
• m is an integer.gtoreq.2, provided that the groups R, R', R", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain;
• n is an integer.gtoreq.0.ltoreq.2;
• o is an integer.gtoreq.1.ltoreq.m;
• "M" is a metallic moiety;
• or a pharmaceutically acceptable salt thereof in which said metallic moiety is paramagnetic, and recording the MR image of an internal region of said subject.

A method of enhancing a sonographic image of an internal region of a subject comprising administering to a subject an effective amount of the complex of the formula (II);

• ##STR14## in which, "B" is a saturated or unsaturated aliphatic or aromatic hydrocarbon backbone comprising 1-20 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• "P" is a polypeptide comprising 2-100 amino acids, said polypeptide capable of targeting particular cells, tissues or organs of the body;
• "A" may be the group --NR'--NR'-- or the group --NR'--NR"--L-- in which L may be an aliphatic or aromatic linker group comprising 1-12 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• R, R', R" may be the same or different and may be hydrogen or an aliphatic group comprising 1-6 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• and
• m is an integer.gtoreq.2, provided that the groups R, R', R", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain;
• n is an integer.gtoreq.0.ltoreq.2;
• o is an integer.gtoreq.1.ltoreq.m;
• "M" is a metallic moiety;
• or a pharmaceutically acceptable salt thereof and recording the sonographic image of an internal region of said subject.

A method of enhancing an X-ray image of an internal region of a subject comprising administering to a subject an effective amount of the complex of the formula (II):

• ##STR15## in which, p1 "B" is a saturated or unsaturated aliphatic or aromatic hydrocarbon backbone comprising 1-20 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• "P" is a polypeptide comprising 2-100 amino acids, said polypeptide capable of targeting particular cells, tissues or organs of the body;
• "A" may be the group --NR'--NR'-- or the group --NR'--NR"--L-- in which L may be an aliphatic or aromatic linker group comprising 1-12 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• R, R', and R" may be the same or different and may be hydrogen or an aliphatic group comprising 1-6 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• and
• m is an integer.gtoreq.2, provided that the groups R, R', R", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain;
• n is an integer.gtoreq.0.ltoreq.2;
• o is an integer.gtoreq.1.ltoreq.m;
• "M" is a metallic moiety;
• or a pharmaceutically acceptable salt thereof and recording the X-ray image of an internal region of said subject.

A pharmaceutical kit comprising a predetermined amount of the compound of the formula (I):

• ##STR16## in which, "B" is a saturated or unsaturated aliphatic or aromatic hydrocarbon backbone comprising 1-20 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• "P" is a polypeptide comprising 2-100 amino acids, said polypeptide capable of targeting particular cells, tissues or organs of the body;
• "A" may be the group --NR'--NR"-- or the group --NR,NR"--L-- in which L may be an aliphatic or aromatic linker group comprising 1-12 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• R,R', and R" may be the same or different and may be hydrogen or an aliphatic group comprising 1-6 carbon atoms and, optionally, one or more heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur;
• m is an integer .gtoreq.2, provided that the groups R, R', r", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain;
• n is an integer .gtoreq.0.ltoreq.2;
• or a pharmaceutically acceptable salt thereof, and, optionally, a pharmaceutically acceptable carrier, stabiizer, or preservative.