LET INTRODUCTION: Ionizing radiation deposits energy at a constant rate as it travels through matter & this rate is defined as Linear Energy Transfer (LET). Low LET (Sparsely Ionizing Radiation, SIR) such as X-rays or γ-rays deposit their energy less densely per unit length of tissue. High LET or Densely Ionizing Radiation (DIR) such as neutrons deposit their energy very densely per unit length of tissue. Equal doses of radiation of differing LET do not produce the same biological response in tissues. CONCEPT OF LET: LET is defined to be the average energy imparted locally to the absorbing medium per unit length of track. The unit in which LET is commonly expressed is keV / μm (the kilo-electron volt being a unit of energy & the micron a unit of length). It may be emphasized that LET is very much an average quantity. There are regions along the track where, for a considerable distance on the microscopic scale, no energy at all is deposited. There are other regions where a cluster of ionizations occur & where, therefore, a large amount of energy is deposited in a small distance. LET OF SOME IONIZING RADIATION: • 60Co : 0.2keV / μm. • 250 keV X-ray: 2keV / μm. • 14 MeV neutrons: 75keV / μm. In general, for a given type of radiation, the LET goes down as the energy goes up. For example, 250 keV X-rays have a higher LET than cobalt gamma rays. Similarly, for a given type of charged particle, like an α particle, a high-energy particle has a lower LET than a low-energy particle. LET & SINGLE DOSE CSC: It is the basis for comparison of the radiosensitivity of different cell populations exposed to different forms of radiation under different environmental condition. Effect of slowly ionizing [low LET] & densely ionizing [high LET] radiation on single dose CSC: • In DIR à high LET – greater efficiency of cell killing for a giving level of dose. Size of Dq is less – slope of curve is steeper. In fact, practically – the only parameter is D0. • In SIR à low LET, wider shoulder – slope of curve is less steep. So, all 3 parameters – Dq, n , D0. So, it can be stated that as the LET of the radiation increases, the slope of the survival curve gets progressively steeper, while the shoulder gets smaller. -2- LET & FRACTIONATION: • In fractionated radiotherapy, both recovery [Small no of # -- large dose/ # -- small overall treatment time] & repopulation [large no of # -- small dose/ # -- large overall treatment time] is moreà extra dose is necessary for same effect. • At 2000cGy: Surviving fraction. Single # à 4.8 X 10-7. 400cGy / # X 5à 10-5. 200cGy / # X 10 à 9 X 10-4. • Recovery is low in high LET, densely ionizing radiation. So, low dose is necessary than SIR (low LET) in fractionated radiotherapy. • When a dose of x-rays or of neutrons is split up in multiple fractionations, separated in sufficient time, so that sub-lethal damage is completed, the shoulder of the dose-response curve must be re-expressed with each fraction. -3- RBE: The relative biologic effectiveness (RBE) is a measure of the ability of radiations with different LETs to produce the same biological effect under the same conditions. A 250 KV X-ray beam is generally used as the reference source for comparison. For example, if a 50% cell kill is achieved by 600 cGy of 250KV x-ray & 200 cGy of neutron under similar experimental conditions, the RBE of neutron is 3. In other word, the test radiation (neutron) is thrice as effective as the reference radiation (250KV x-ray). RBE of 250 KV X-ray beam = 1. RBE of telecobalt = 0.9. RBE of 4 MeV = 0.85. RBE of 20 MeV = 0.80. RBE & LET: The variation of RBE as a function of LET has a characteristic shape. As LET increases from 1 to 10 keV / μm, RBE increases slowly but steadily, then increases more rapidly beyond 10 keV / μm to reach a peak, about 100 keV / μm, after which RBE tends to fall again for higher values of LET. The decrease of RBE at very high values of LET is generally attributed to the phenomenon of ‘overkill’. At these very high LETs, the density of ionization is such that, if a charged particle track passes through a cell, it deposits far more energy than is required to kill the cell. Consequently, much of this energy is ‘wasted’, since the cell cannot be killed more than once. OER: Oxygen Enhancement Ratio (OER) is expressed as the ratio of doses in absence & presence of oxygen required to produce equal biologic effect. At high doses, the OER has a value of between 2.5 & 3 and it may be reduced to 2 for doses < 2 Gy. Cells irradiated in the presence of molecular oxygen are more sensitive to killing by x-rays than cells that are hypoxic. The proportion of hypoxic cells appears to be usually in the range of 10% to 15%. LET & OER: As LET increases, there is a corresponding decrease in the dependence of cell killing on the presence of molecular oxygen. Low LET radiations are characterized by a large OER of between 2.5 & 3. Heavy charged particles with a LET of several hundred keV / μm have an OER 0f unity. Neutrons with a LET of about has keV / μm show an intermediate OER of about 1.6. It may be noted that the rapid increase of RBE & the rapid fall of OER both occur at about same LET [100keV / μm]. -4- BORON NEUTRON CAPTURE THERAPY: The fundamental concept of boron neutron capture therapy is the production of high LET particles ( 7Li3+ & 4He2t) when one ‘tags’ or ‘labels’ a tumor cell with a compound having a large cross-section capable of capturing a ‘slow’ neutron. After the compound (say Boron) captures the neutron, it goes into an excited state. The excited fission of the 11B nucleus will release energy, which drives the heavy ion products over short distance to the dimensions of a cell. A 0.48 MeV photon is also produced in 94% of the fission events. This is useful for monitoring the reaction but is of little consequence for cell killing. The tracts from boron’s interaction with neutrons are straight & are consistent with the formation of two particles traveling in opposite trajectories. In photographic gelatin, their average travel distance is 7.6μm. The boron neutron capture process is highly localized. In principle, one could kill a tumor cell containing boron while sparing an adjacent normal cell that does not contain boron. Diagramatic representation: Slow or thermal neutron Bomberdment Tumor cell tagged with stable boron 10 Excited boron 11 Fission Lithium 7 nuclei + α- particle (high LET radiation)
Posted on: Sun, 29 Sep 2013 07:43:57 +0000
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