Prostate-cancer-targeted N-(2-hydroxypropyl)methacrylamide copolymer/docetaxel conjugates

Macromol Biosci. 2012 Mar;12(3):412-22. doi: 10.1002/mabi.201100340.

Abstract

Biodistribution, pharmacokinetics, and efficacy of prostate-cancer-targeted HPMA copolymer/DTX conjugates are evaluated in nude mice bearing prostate cancer C4-2 xenografts. PSMA-specific monoclonal antibodies 3F/11 are used as the targeting moiety. Control conjugates tumor accumulation to total background organs (heart, lung, kidney, liver, spleen and blood) accumulation increase substantially with time for the targeted conjugate, and the ratio at 48 h is 7-fold higher than that at 6 h. Preliminary evaluation of the efficacy of the conjugates in vivo show tumor growth inhibition for all HPMA copolymer/DTX conjugates.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acrylamides / chemical synthesis*
  • Acrylamides / pharmacokinetics
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antigens, Surface / immunology
  • Docetaxel
  • Drug Delivery Systems*
  • Glutamate Carboxypeptidase II / immunology
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacokinetics*
  • Iodine Radioisotopes
  • Male
  • Mice
  • Mice, Nude
  • Polymers / chemical synthesis*
  • Polymers / pharmacokinetics
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology
  • Taxoids / chemistry*
  • Taxoids / pharmacokinetics
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Acrylamides
  • Antibodies, Monoclonal
  • Antigens, Surface
  • Immunoconjugates
  • Iodine Radioisotopes
  • Polymers
  • Taxoids
  • Docetaxel
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • N-(2-hydroxypropyl)methacrylamide