Measurement of renal tumour and normal tissue perfusion using positron emission tomography in a phase II clinical trial of razoxane.
Measurement of tumour and normal tissue perfusion in vivo in cancer patients will aid the clinical development of antiangiogenic and antivascular agents. We investigated the potential antiangiogenic effects of the drug razoxane by measuring the changes in parameters estimated from H(2)(15)O and C(15)O positron emission tomography (PET) to indicate alterations in vascular physiology. The study comprised 12 patients with primary or metastatic renal tumours >3 cm in diameter enrolled in a Phase II clinical trial of oral razoxane. Perfusion, fractional volume of distribution of water (VD) and blood volume (BV) were measured in tumour and normal tissue before and 4-8 weeks after treatment with 125 mg twice-daily razoxane. Renal tumour perfusion was variable but lower than normal tissue: mean 0.87 ml min(-1) ml(-1) (range 0.33-1.67) compared to renal parenchyma: mean 1.65 ml min(-1) ml(-1) (range 1.16-2.88). In eight patients, where parallel measurements were made during the same scan session, renal tumour perfusion was significantly lower than in normal kidney (P=0.0027). There was no statistically significant relationship between pretreatment perfusion and tumour size (r=0.32, n=13). In six patients scanned before and after razoxane administration, there was no statistically significant change in tumour perfusion: mean perfusion pretreatment was 0.81 ml min(-1) ml(-1) (range 0.46-1.26) and perfusion post-treatment was 0.72 ml min(-1) ml(-1) (range 0.51-1.15, P=0.15). Tumour VD and BV did not change significantly following treatment: mean pretreatment VD=0.66 (range 0.50-0.87), post-treatment VD=0.71 (range 0.63-0.82, P=0.22); pretreatment BV=0.18 ml ml(-1) (range 0.10-0.25), post-treatment BV=0.167 ml ml(-1) (range 0.091-0.24, P=0.55). Tumour perfusion, VD and BV did not change significantly with tumour progression. This study has shown that H(2)(15)O and C(15)O PET provide useful in vivo physiological measurements, that even highly angiogenic renal cancers have poor perfusion compared to surrounding normal tissue, and that PET can provide valuable information on the in vivo biology of angiogenesis in man and can assess the effects of antiangiogenic therapy.
Anderson
H
H
Cancer Research UK PET Oncology Group, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. anne.mason@man.ac.uk
Yap
J T
JT
Wells
P
P
Miller
M P
MP
Propper
D
D
Price
P
P
Harris
A L
AL
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002248:Carbon Monoxide; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D009389:Neovascularization, Pathologic; D010104:Oxygen Radioisotopes; D011929:Razoxane / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012039:Regional Blood Flow; D014055:Tomography, Emission-Computed; D014867:Water
D000970:Antineoplastic Agents; D010104:Oxygen Radioisotopes; D014867:Water; D011929:Razoxane; D002248:Carbon Monoxide