BioProton: Biologically relevant dose for Proton Therapy Planning

BioProton：质子治疗计划的生物学相关剂量

• 批准号: EP/S024344/1
• 负责人: Karen Kirkby
• 金额: $ 177.7万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS024344%2F1
• 关键词: BioProton; Biologically; relevant; dose; Proton

Oxygen plays an important role in life on earth. The air that we breathe provides cells with the oxygen required for energy production. This need for oxygen increases for cells that rapidly multiply such as those associated with cancer; however, the supply is limited. As a tumour increases in size not all parts will be located near to vessels carrying oxygen rich blood. This results in a reduction in the oxygen levels in cells located furthest away from the blood vessel. It has been shown that these cells with low levels of oxygen (termed hypoxic) are more resistant to damage from radiation than those that are well oxygenated. This is also known to be the case for irradiation with protons. In proton therapy, a beam of protons is fired at the tumour in order to destroy the DNA in the cancerous cells, thus killing the tumour. The amount of energy and number of protons required to achieve this is determined by the tumour volume. Currently in proton therapy the tumour is irradiated such that the whole tumour volume receives the same dose (energy deposited per unit mass). If, however, parts of the irradiated tumour are more resistant to the radiation than others this technique of delivering a uniform dose across the tumour volume is not optimal.The research planned in this project aims to address this through the use of computer modelling and imaging to produce a method of increasing the dose to those low-oxygen radiation-resistant parts of the tumour whilst delivering an appropriately lower dose to the well oxygenated regions. This advancement will improve proton beam therapy and benefit any patient undergoing this form of cancer treatment. The benefits will include increased chance of survival and fewer side effects associated with the treatment

氧气在地球上的生命中起着重要的作用。我们呼吸的空气为细胞提供能量产生所需的氧气。对于快速繁殖的细胞，例如与癌症相关的细胞，这种对氧气的需求增加;然而，供应是有限的。随着肿瘤大小的增加，并非所有部分都位于携带富氧血液的血管附近。这导致位于离血管最远的细胞中的氧水平降低。已经表明，这些细胞与低水平的氧气（称为缺氧）更能抵抗辐射的损害比那些充分氧化。这也是已知的质子辐照的情况。在质子治疗中，质子束被发射到肿瘤上，以破坏癌细胞中的DNA，从而杀死肿瘤。实现这一点所需的能量和质子数由肿瘤体积决定。目前在质子治疗中，肿瘤被照射，使得整个肿瘤体积接收相同的剂量（每单位质量沉积的能量）。但是，如果受照射的肿瘤部分比其他部分对辐射的抵抗力更强，这种在肿瘤体积内提供均匀剂量的技术并不是最佳的。该项目计划的研究旨在通过使用计算机建模和成像来解决这个问题，以产生一种增加低氧辐射剂量的方法-肿瘤的耐药部分，同时向氧合良好的区域递送适当较低的剂量。这一进步将改善质子束治疗，并使任何接受这种形式癌症治疗的患者受益。好处将包括增加生存机会和减少与治疗相关的副作用

项目成果

Clinically relevant nanodosimetric simulation of DNA damage complexity from photons and protons.

• DOI: 10.1039/c8ra10168j
• 发表时间: 2019-02-22
• 期刊: RSC ADVANCES
• 影响因子: 3.9
• 作者: Henthorn, N. T.;Warmenhoven, J. W.;Sotiropoulos, M.;Aitkenhead, A. H.;Smith, E. A. K.;Ingram, S. P.;Kirkby, N. F.;Chadwick, A. L.;Burnet, N. G.;Mackay, R. I.;Kirkby, K. J.;Merchant, M. J.
• 通讯作者: Merchant, M. J.

Hi-C implementation of genome structure for in silico models of radiation-induced DNA damage.

• DOI: 10.1371/journal.pcbi.1008476
• 发表时间: 2020-12
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Ingram SP;Henthorn NT;Warmenhoven JW;Kirkby NF;Mackay RI;Kirkby KJ;Merchant MJ
• 通讯作者: Merchant MJ

The suitability of micronuclei as markers of relative biological effect.

• DOI: 10.1093/mutage/geac001
• 发表时间: 2022-04-02
• 期刊: Mutagenesis
• 影响因子: 2.7
• 作者: Heaven CJ;Wanstall HC;Henthorn NT;Warmenhoven JW;Ingram SP;Chadwick AL;Santina E;Honeychurch J;Schmidt CK;Kirkby KJ;Kirkby NF;Burnet NG;Merchant MJ
• 通讯作者: Merchant MJ

A computational approach to quantifying miscounting of radiation-induced double-strand break immunofluorescent foci.

• DOI: 10.1038/s42003-022-03585-5
• 发表时间: 2022-07-14
• 期刊: Communications biology
• 影响因子: 5.9