title: Magnetic resonance imaging of therapy-induced necrosis using gadolinium-chelated polyglutamic acids.
abstract: OBJECTIVE
  Necrosis is the most common morphologic alteration found in tumors and surrounding normal tissues after radiation therapy or chemotherapy. Accurate measurement of necrosis may provide an early indication of treatment efficacy or associated toxicity. The purpose of this report is to evaluate the selective accumulation of polymeric paramagnetic magnetic resonance (MR) contrast agents--gadolinium p-aminobenzyl-diethylenetriaminepentaacetic acid-poly(glutamic acid) (L-PG-DTPA-Gd and D-PG-DTPA-Gd)--in necrotic tissue.
  
  
  METHODS
  Two different solid tumor models, human Colo-205 xenograft and syngeneic murine OCA-1 ovarian tumors, were used in this study. Necrotic response was induced by treatment with poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL). T(1)-weighted spin-echo images were obtained immediately and up to 4 days after contrast injection and compared with corresponding histologic specimens. Two low-molecular-weight contrast agents, DTPA-Gd and oligomeric(L-glutamic acid)-DTPA-Gd, were used as nonspecific controls.
  
  
  RESULTS
  Initially, there was minimal tumor enhancement after injection of either L-PG-DTPA-Gd or D-PG-DTPA-Gd, but rapid enhancement after injection of low-molecular-weight agents. However, polymeric contrast agents, but not low-molecular-weight contrast agents, caused sustained enhancement in regions of tumor necrosis in both tumors treated with PG-TXL and untreated tumors. These data indicate that high molecular weight, rather than in vivo biodegradation, is necessary for the specific localization of polymeric MR contrast agents to necrotic tissue. Moreover, biotinylated L-PG-DTPA-Gd colocalized with macrophages in the tumor necrotic areas, suggesting that selective accumulation of L- and D-PG-DTPA-Gd in necrotic tissue was mediated through residing macrophages.
  
  
  CONCLUSIONS
  Our data suggest that MR imaging with PG-DTPA-Gd may be a useful technique for noninvasive characterization of treatment-induced necrosis.
authors: Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Edward F
authors: EF
authors: Jackson
authors: Emilio
authors: E
authors: Esparza-Coss
authors: Xiaoxia
authors: X
authors: Wen
authors: Chaan S
authors: CS
authors: Ng
authors: Sherita L
authors: SL
authors: Daniel
authors: Roger E
authors: RE
authors: Price
authors: Belinda
authors: B
authors: Rivera
authors: Chusilp
authors: C
authors: Charnsangavej
authors: Juri G
authors: JG
authors: Gelovani
authors: Chun
authors: C
authors: Li
mesh_terms: D000818:Animals; D002614:Chelating Agents; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000532:radiotherapy; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000532:radiotherapy; D011099:Polyglutamic Acid; D011833:Radiation Injuries, Experimental / Q000175:diagnosis*
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D011099:Polyglutamic Acid; D019786:Gadolinium DTPA