Measurement of renal tumour and normal tissue perfusion using positron emission tomography in a phase II clinical trial of razoxane.
Measurement of renal tumour and normal tissue perfusion using positron emission tomography in a phase II clinical trial of razoxane.
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DOI：
10.1038/sj.bjc.6601105
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发表时间：
2003-07-21
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
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测量肿瘤和正常组织灌注在体内癌症患者将有助于临床开发的抗血管生成和抗血管剂。我们通过测量H215 O和C15 O正电子发射断层扫描（PET）估计的参数变化来研究药物雷佐生的潜在抗血管生成作用，以指示血管生理学的改变。该研究包括12名患有直径>3 cm的原发性或转移性肾肿瘤的患者，这些患者参加了口服雷佐生的II期临床试验。在用125 mg每日两次雷佐生治疗之前和治疗后4-8周，测量肿瘤和正常组织中的灌注、水分布分数容积（VD）和血容量（BV）。肾肿瘤灌注变化不定，但低于正常组织：平均0.87 ml min−1 ml−1（范围0.33-1.67），而肾实质：平均1.65 ml min−1 ml−1（范围1.16-2.88）。在8例患者中，在同一扫描期间进行平行测量，肾肿瘤灌注显著低于正常肾（P=0.0027）。治疗前灌注与肿瘤大小之间无统计学显著相关性（r=0.32，n=13）。在雷佐生给药前后扫描的6例患者中，肿瘤灌注无统计学显著性变化：治疗前平均灌注为0.81 ml min−1 ml−1（范围0.46-1.26），治疗后灌注为0.72 ml min−1 ml−1（范围0.51-1.15，P=0.15）。治疗后肿瘤VD和BV无显著变化：平均治疗前VD=0.66（范围0.50-0.87），治疗后VD=0.71（范围0.63-0.82，P=0.22）;治疗前BV=0.18 ml ml−1（范围0.10-0.25），治疗后BV=0.167 ml ml−1（范围0.091-0.24，P=0.55）。肿瘤灌注、VD和BV随肿瘤进展无显著变化。这项研究表明，H215 O和C15 O PET提供了有用的体内生理测量，即使是高度血管生成的肾癌与周围正常组织相比也具有较差的灌注，并且PET可以提供关于人体血管生成的体内生物学的有价值的信息，并且可以评估抗血管生成治疗的效果。
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 H215O and C15O 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 H215O and C15O 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.
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影响因子：
64.8
作者：
SHARPE, HBA;FIELD, EO;HELLMANN, K
通讯作者：
HELLMANN, K
影响因子：
2.6
作者：
LAMMERTSMA, AA;WISE, RJS;JONES, T
通讯作者：
JONES, T
影响因子：
37.8
作者：
ARAUJO, LI;LAMMERTSMA, AA;MASERI, A
通讯作者：
MASERI, A
影响因子：
6.4
作者：
Boehle, AS;Kurdow, R;Neumaier, M
通讯作者：
Neumaier, M
影响因子：
1.5
作者：
Anderson, H;Price, P
通讯作者：
Price, P