Thrall D E, McEntee M C, Cline J M, Raleigh J A
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Int J Radiat Oncol Biol Phys. 1994 Feb 1;28(3):649-59. doi: 10.1016/0360-3016(94)90190-2.
The purpose of this work was to evaluate multiple injections of CCI-103F, a marker of hypoxia, as a method to quantify alterations in tumor hypoxia during irradiation.
Twelve dogs with spontaneous solid tumors were given intravenous CCI-103F, and tumor biopsies were taken at various times after injection. Two tumor samples were taken at each biopsy procedure. CCI-103F antigen concentration was quantified by ELISA. Four of the dogs were given one injection of CCI-103F, and the other eight received two injections. In dogs receiving two injections, CCI-103F was administered before irradiation and 7 days later, following a total dose of 15.0 Gy. Plasma CCI-103F pharmacokinetics were assessed in dogs receiving two injections.
CCI-103F antigen was detectable in the initial biopsy in each of the four dogs receiving one injection, and the amount of detectable antigen decreased in subsequent biopsies with an initial half life of approximately 19 h. This suggests that multiple injections of CCI-103F could be used in the same subject to monitor tumor hypoxia as a function of time or during a course of treatment. In the eight dogs receiving two injections of CCI-103F, the CCI-103F antigen concentration in the 24 h samples ranged from 4.66-151.9 mumol CCI-103F antigen/kg tumor, a difference of a factor of approximately 33. The ratio of maximum to minimum concentration of CCI-103F antigen in 51 paired biopsy samples ranged from 1.01-4.07, with a mean (+/- s.d.) of 1.67 +/- 0.67. Seventy-five percent of the ratios were < or = 2.02. There was no apparent relationship between the magnitude of the ratio, i.e., intratumoral variation, and tumor volume or the absolute tumor concentration of CCI-103F antigen. Absolute radiobiologic hypoxic fraction was not known but the pattern of change in amount of intratumoral CCI-103F antigen in dogs given two injections of CCI-103F was consistent with little change in pretreatment oxygen status in six dogs, and an increase in tumor oxygenation in two dogs.
It appears possible to obtain an estimate of the change in tumor hypoxia in an individual tumor over time by assaying biopsy samples for CCI-103F antigen concentration.
本研究旨在评估多次注射缺氧标志物CCI - 103F作为量化放疗期间肿瘤缺氧变化的一种方法。
对12只患有自发性实体瘤的犬静脉注射CCI - 103F，并在注射后的不同时间采集肿瘤活检样本。每次活检取两个肿瘤样本。通过酶联免疫吸附测定法（ELISA）对CCI - 103F抗原浓度进行定量。4只犬注射一次CCI - 103F，另外8只接受两次注射。在接受两次注射的犬中，在总剂量为15.0 Gy的放疗前及放疗7天后注射CCI - 103F。对接受两次注射的犬评估血浆CCI - 103F的药代动力学。
在接受一次注射的4只犬中，首次活检时均可检测到CCI - 103F抗原，随后活检中可检测到的抗原量减少，初始半衰期约为19小时。这表明多次注射CCI - 103F可用于同一受试者，以监测肿瘤缺氧随时间或在治疗过程中的变化。在接受两次注射CCI - 103F的8只犬中，24小时样本中的CCI - 103F抗原浓度范围为4.66 - 151.9 μmol CCI - 103F抗原/ kg肿瘤，相差约33倍。在51对活检样本中，CCI - l03F抗原的最大浓度与最小浓度之比范围为1.01 - 4.07，平均（±标准差）为1.67 ± 0.67。75%的比值≤2.02。比值大小（即肿瘤内变化）与肿瘤体积或CCI - 103F抗原的绝对肿瘤浓度之间无明显关系。虽然绝对放射生物学缺氧分数未知，但接受两次注射CCI - 103F的犬肿瘤内CCI - 103F抗原量的变化模式表明，6只犬的预处理氧状态变化不大，2只犬的肿瘤氧合增加。
通过检测活检样本中的CCI - 103F抗原浓度，似乎有可能估计个体肿瘤中肿瘤缺氧随时间的变化。
