A long-circulating co-polymer in "passive targeting" to solid tumors.
A co-polymer of O-methyl polyethylene(glycol)-O'-succinate (MPEGs, m.w. 5100) and poly-l-lysine (PL, median m.w. 32700, degree of polymerization 256) has been synthesized by covalent grafting. The resultant MPEGs-PL (30% modification degree of epsilon-amino groups) had a hydrodynamic diameter corresponding to a 690 kD protein. Free amino groups (180/mol of the co-polymer) were used for conjugation of diethylene pentaacetic or succinic acid residues to MPEGs-PL. The potential of the resultant compound as a carrier of therapeutic and diagnostic drugs was studied using a rodent carcinoma models. The co-polymer had a blood pool half-life of 36h in adenocarcinoma-bearing rats. Radioactively labeled preparations were resistant to trans-chelation with apotransferrin and stable in blood for 24 h. The co-polymer accumulated in solid tumors at the level of 1.5-2% injected dose/g of tumor in 24 h. At that time, 34-40% of the accumulated polymer was associated with tumor cell fraction. The co-polymer non-covalently associated with cis-diamminedichloroplatinum(II), showed a cytostatic effect against mouse F9 carcinoma, and induced a reversal in tumor growth after intravenous administration.
Bogdanov
A
A
Department of Radiology, Massachusetts General Hospital, Boston 02129, USA. abogdanov@helix.mgh.harvard.edu
Wright
S C
SC
Marecos
E M
EM
Bogdanova
A
A
Martin
C
C
Petherick
P
P
Weissleder
R
R
D000818:Animals; D004337:Drug Carriers; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011107:Polylysine / Q000008:administration & dosage*; D051381:Rats; D016284:Technetium Tc 99m Pentetate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; C094185:technetium Tc 99m methoxypoly(ethylene)glycol-polylysyl-DTPA; D011107:Polylysine; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D016284:Technetium Tc 99m Pentetate