Biologically compatible linear block copolymers of polyalkylene oxide and peptide units

DETAILED DESCRIPTION INCLUSIVE OF PREFERRED EMBODIMENTS We have discovered that linear block copolymers comprising blocks of poly(alkylene oxide) (PAGs) and peptides attached via --CH.
sub.
2 CHOHCH.
sub.
2 N(R)-- based linking groups are useful as imaging agents, prodrugs, drugs and drug delivery systems.
Preferred copolymers are of the formula; --(PAG)N(R)CH.
sub.
2 CHOHCH.
sub.
2 OC.
sub.
6 H.
sub.
4 CO(Peptide)NH(CH.
sub.
2).
sub.
p C.
sub.
6 H.
sub.
4 OCH.
sub.
2 CHOHCH.
sub.
2 N(R)-- Formula A or --(PAG)CH.
sub.
2 CHOHCH.
sub.
2 N(R)CH.
sub.
2 CO(Peptide)NH(CH.
sub.
2).
sub.
p NHCOCH.
sub.
2 NR CH.
sub.
2 CHOHCH.
sub.
2 -- Formula B wherein R is a 1-4 carbon alkyl; and p is from 1 to 6 and the peptide is preferably Gly-Phe-Leu-Gly or Lys-Gly-Phe-Leu-Gly.
The compounds can be tailored for specific uses by altering the size of the polymer or altering the peptide composition to provide differing blood pool residence time, enzymatic breakdown rates, and tissue distributions.
As an imaging agent, said composition preferably has a molecular weight of at least about 5000 and a metal ion useful as a contrast enhancer, fluorophore or x-ray opaque ion associated therewith, and thus suitable for use as an agent for diagnostic imaging.
An imaging metal is defined as a metal useful in x-ray imaging or a metal useful in magnetic resonance imaging, preferably a paramagnetic metal and more preferably a lanthanide metal or transition metal; or a metal useful in fluorescence imaging, preferably a lanthanide metal, most preferably Europium.
This invention further provides a method of performing a diagnostic imaging procedure in a body comprising administering to the body a contrast enhancing amount of the polymer described above, and then exposing the body to a magnetic resonance measurement step to image at least a portion of the body.
It is a particularly advantageous feature that the polymeric chelates of this invention provide effective imaging contrast enhancement of the blood pool within the vascular system for remarkably long periods of time