Measurement of proliferation activity in human melanoma xenografts by magnetic resonance imaging

Abstract

Tumor proliferation may be predictive for malignant progression and response to fractionated therapy of cancer. The purpose of the present work was to investigate whether the proliferation activity of solid tumors can be assessed in vivo from the proton relaxation times, T 1 and T 2. Tumors of four amelanotic human melanoma xenograft lines were studied. Three parameters were used to represent tumor proliferation activity; the volume doubling time, T vol, the potential doubling time, T pot, and the fraction of cells in S-phase. T vol was determined from volumetric growth data. T pot and S-phase fraction were determined by flow cytometric analysis of tumor cells after bromodeoxyuridine (BrdU) incorporation in vivo. T 1 and T 2 were measured by 1H-MRI in vivo, using spin-echo pulse sequences. The proliferation parameters and relaxation times differed considerably among the tumor lines. Significant correlations were found between the proliferation parameters and the relaxation times, regardless of whether T vol, T pot, or S-phase fraction was considered. Tumors with short T vol and T pot and high S-phase fraction had long T 1 and T 2 compared to tumors with long T vol and T pot and low S-phase fraction. The elongated T 1 and T 2 of fast growing tumors were probably due to increased interstitial and/or intravascular water content. The present results suggest that in vivo spin-echo 1H-MRI can be used to discriminate between tumors of high and low proliferation activity.