Assessment of 11C-labeled-4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline as a positron emission tomography agent to monitor epidermal growth factor receptor expression

Cancer Sci. 2007 Sep;98(9):1413-6. doi: 10.1111/j.1349-7006.2007.00562.x. Epub 2007 Jul 11.

Abstract

The aim of the present study was to investigate the biodistribution of (11)C-labeled-4-N-(3-bromoanilino), 6,7-dimethoxyquinazoline ((11)C-PD153035) and the relationship between accumulation of the tracer and epidermal growth factor receptor (EGFR) expression levels. Biodistribution studies of (11)C-PD153035 were performed in tumor-bearing nude mice. The amount of radioactivity in the lungs was small while concentrations were highest in the liver and intestine. From in vitro studies, the level of (11)C-PD153035 accumulation was detected in MDA-MB-468, A549, and MDA-MB-231 cells. The uptake of (11)C-PD153035 in cells was closely correlated with the EGFR expression level of cells (r(2) = 0.85; P < 0.001), and the results obtained in excised tumors were also significantly correlated (r(2) = 0.63; P = 0.003). Binding in MDA-MB-468, A549, and MDA-MB-231 tumors was reduced to background level at 60 min post injection( 11)C-PD153035 by pretreatment with cold PD153035. The present study showed that whether in vitro or ex vivo the uptake of (11)C-PD153035 closely correlated with EGFR expression levels. In contrast, blocking studies revealed specific binding in the three kinds of tumors. Thus (11)C-PD153035 may be used as a positron emission tomography tracer to yield useful information about tumors, particularly for lung cancer with different EGFR expression levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Carbon Radioisotopes / metabolism*
  • Cell Line, Tumor
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Lung Neoplasms / metabolism
  • Mammary Neoplasms, Experimental / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Organ Specificity
  • Positron-Emission Tomography
  • Quinazolines / metabolism*

Substances

  • Biomarkers, Tumor
  • Carbon Radioisotopes
  • Quinazolines
  • ErbB Receptors
  • 4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline