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

Tumor proliferation may be predictive for malignant progression and respons e to fractionated therapy of cancer. The purpose of the present work was to investigate whether the proliferation activity of solid tumors can be asse ssed in vivo from the proton relaxation times, T-1 and T-2. Tumors of four amelanotic human melanoma xenograft lines were studied. Three parameters we re 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 b y H-1-MRI in vivo, using spin-echo pulse sequences. The proliferation param eters and relaxation times differed considerably among the tumor lines. Sig nificant correlations were found between the proliferation parameters and t he relaxation times, regardless of whether T-vol, T-pot, or S-phase fractio n,vas considered. Tumors with short T-vol and T-pot and high S-phase fracti on had long T-1 and T-2 compared to tumors with long T-vol and T-pot and lo w S-phase fraction. The elongated T-1 and T-2 of fast growing tumors were p robably due to increased interstitial and/or intravascular water content. T he present results suggest that in vivo spin-echo H-1-MRI can be used to di scriminate between tumors of high and low proliferation activity. (C) 1999 Elsevier Science Inc.