Martin Zweifel1, Daniel Patterson1, N. Jane Taylor2, J. James Stirling2, Ian C. Simcock2, David J. Collins3, James A. d'Arcy3, Martin O. Leach3, Gordon J. Rustin1, Anwar R. Padhani2
1Dept of Medical Oncology, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, United Kingdom; 2Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, United Kingdom; 3CRUK-EPSRC Cancer Imaging Centre, Institute of Cancer Research & Royal Marsden Hospital, Sutton, Surrey SM2 5PT, United Kingdom
Repeated R2* measurements were performed during the first 4h after administration of the vascular disrupting agent OXi4503 (combretastatin A1 phosphate, CA1P) in the first in man phase I clinical trial in 22 patients with advanced tumours. DCE-MRI sequences were also performed at 4h. There was a significant dose Ktrans-response relationship. Significant increases in R2* at 3h and 4h were only seen in the intermediate dose/intermediate Ktrans-decrease group. While at intermediate doses, deoxygenated erythrocytes may become entrapped within the tumour vasculature, vascular collapse might result in the emptying of red blood cells and paradoxically not changing the R2* at higher doses.