Vanneste Ben G L, Lutgens Ludy, Van Limbergen Evert J
Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
Clin Transl Radiat Oncol. 2022 Jan 5;33:53-56. doi: 10.1016/j.ctro.2021.12.009. eCollection 2022 Mar.
To determine a dose response relationship of disintegration of a hyaluronic acid (HA) and hyaluronidase (HAS) used in prostate cancer radiotherapy.
Five in-vitro models are applicated with 3 ml (ml) HA. For dissolution varying doses of HAS were used: 6 ml, 3 ml, 1.5 ml, and 0 ml. One ml contains 150 International Units (IU). Each HAS was added with saline till the complementary amount of 6 ml. One phantom was solely implanted with a HA 3 ml acting as a control. Length, width and height were measured on different time points: 1st day 4 times, 2nd day 3 times, third day 2 times, and then once daily during one week, with a final measurement 2 weeks after implantation. The experiments were performed in duplicate to exclude variations and confirm the results.
The fastest dissolution was observed with the highest concentration of HAS, already observed at the first time point 2 h after implantation, with volume decrease of 50% on the second day, and less than 1 ml residue (33%) on day 4. The 2 other concentrations of HAS also showed a volume decrease, with less than 2 ml (66%) on day 4. All the applied quantities of HAS are observed with a residue of less than 1 ml after 7 days. After 14 days the control phantom and the saline filled one remains on steady state volume (3 ml).
A dose response was observed by HAS injection: highest volumes of HAS dissolute most swiftly. Using a ratio of HA:HAS of 1:2 results in a decrease to half of initial volume within 24 h. This is of special interest when used in clinical practice following erroneous positioning, and dissolution is urgently needed.
确定用于前列腺癌放疗的透明质酸(HA)与透明质酸酶(HAS)溶解的剂量反应关系。
五个体外模型应用3毫升(ml)HA。为实现溶解,使用了不同剂量的HAS:6毫升、3毫升、1.5毫升和0毫升。每毫升含有150国际单位(IU)。每种HAS均用生理盐水补充至6毫升的总量。一个模型仅植入3毫升HA作为对照。在不同时间点测量长度、宽度和高度:第1天测量4次,第2天测量3次,第3天测量2次,然后在一周内每天测量1次,植入后2周进行最后一次测量。实验重复进行以排除变异并确认结果。
观察到HAS浓度最高时溶解最快,在植入后2小时的第一个时间点就已观察到,第2天体积减少50%,第4天残留量小于1毫升(33%)。其他两种HAS浓度也显示出体积减少,第4天小于2毫升(66%)。所有应用的HAS量在7天后残留量均小于1毫升。14天后,对照模型和填充生理盐水的模型体积保持稳定(3毫升)。
通过注射HAS观察到剂量反应:HAS用量最大时溶解最快。使用HA:HAS比例为1:2可在24小时内使初始体积减少一半。这在临床实践中因定位错误而急需溶解时具有特殊意义。