Analysis of 2-carbon-11-thymidine blood metabolites in PET imaging.
Analysis of 2-carbon-11-thymidine blood metabolites in PET imaging.
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发表时间：
1996-02
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通讯作者：
A. Shields;D. Mankoff;M. Graham;M. Zheng;S. Kozawa;J. Link;K. Krohn
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作者：
A. Shields;D. Mankoff;M. Graham;M. Zheng;S. Kozawa;J. Link;K. Krohn
在环-2位置标记的未标记碳-11-胸苷与PET一起用于肿瘤和组织增殖成像。由于胸苷在体内迅速降解，因此必须考虑代谢产物的产生以充分解释PET数据。方法测定动脉血中胸苷及其代谢产物的时间-活性曲线。处理血液以获得三个输入曲线，包括总活性、去除CO2的活性和完整胸苷中无CO2活性的分数（% Tdr）。结果我们发现，CO2在注射后11分钟达到总血液活性的65%（+/- 12%）的平台。当使用1分钟输注标记胸苷时，至50%降解为胸腺嘧啶和除CO2以外的代谢物的时间（通过HPLC在酸化样品中测量）为2.9 +/- 0.6分钟。我们将血液代谢结果与房室模型拟合。我们发现，我们可以准确地确定% Tdr曲线与少至三个测量点，均方根（RMS）误差为2%的积分曲线，相比，曲线使用所有血液样本（平均每例患者7个样本）。胸苷血液活性的积分作为胸苷模型的输入，因此在DNA合成速率的计算中可以预期类似的误差。我们发现，CO2的测定可以用五个样品完成，在平台%CO2值的RMS误差为4%。结论虽然在解释11 C-胸苷所得结果时必须考虑代谢物，但这些降解曲线的重现性允许使用有限数量的样品来测量胸苷的分解代谢产物。这些来自血液的数据，沿着组织动力学模型，需要计算DNA合成速率。
UNLABELLED Carbon-11-thymidine labeled in the ring-2 position was used with PET to image tumor and tissue proliferation. Since thymidine is rapidly degraded in the body, one must consider the generation of metabolites to fully interpret the PET data. METHODS We have measured the blood time-activity curves of thymidine and its metabolites in arterial blood samples. Blood was processed to obtain three input curves, including the total activity, the activity with CO2 removed and the fraction of CO2-free activity in intact thymidine (% Tdr). RESULTS We found that CO2 reached a plateau of 65% (+/- 12%) of total blood activity by 11 min after injection. When a 1-min infusion of labeled thymidine is used, the time to 50% degradation to thymine and metabolites other than CO2 (measured in acidified samples by HPLC) was 2.9 +/- 0.6 min. We fit the results of the blood metabolism with a compartmental model. We found that we could accurately determine the % Tdr curve with as few as three measured points with an root mean square (RMS) error of 2% in the integrated curve, compared to the curve using all blood samples (mean of seven samples per patient). The integral of thymidine blood activity serves as the input to thymidine models, so similar errors could be expected in calculations of DNA synthetic rates. We found that the determination of CO2 could be accomplished with as few as five samples, with an RMS error of 4% in plateau %CO2 value. CONCLUSION While it is essential to take metabolites into account when interpreting results obtained with 11C-thymidine, the reproducibility of these degradation curves may allow the use of a limited number of samples to measure the catabolic products of thymidine. These data from the blood, along with tissue kinetic models, are needed to calculate DNA synthetic rates.