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RBE and OER Values as a function of neutron energy
Euwp. & Cancer Vol. 10, pp. 297-299. Pergamon Press 1974. Printed in Great Britain
RBE and OER Values as a Function of Neutron Energy* ERIO J. HALL Radiologieal Research Laboratoo, , Department of Radiology. College of Physicians and Surgeons of Columbia University, New York, N.Y. 10032, U.S.A.
Abstract--A nao set of RBE and OER measurements are reportedfor ten neutron energies between 60 ke V and 15 Me V obtained at the Radiologieal Research Accelerator Facili O, at Bro&hav'ea National Laboratory. hi addition two higher energy neutron beams were studied at the Naval Research Laboratory in Washhtgton and at the Texas A & M Cyclotron. Two biological test systems were used, namely growth inhibition of Vicia seedlings and hamster cells cultured in vitro. In the ease of the OER, a minimum rathe of 1"3 was observedfor neutron energies of 220-4.40 kcV. OER increased with neutron energy to a maximum of 1.8for 15 MeV neutrons. A slightly lower value of 1.6 was found to apply to both of the high energy cyclotron-produced neutron beams currently being httroduced for radiotherapy. The plot of RBE as a fiuletion of twutron energy has a similar shape far both biological test systems employed; the maximum RBE occurs at a neutron energy of about 350 keV. The experimental data are consistent with the theoretical predictions made on the basis of mierodosimetrie measurements.
Laboratory, ten neutron energies have been studied ranging from 60 keV to 15 MeV. The characteristics of the beams used are summarized in Table 1. By using suitable targets essentially monoenergetic neutron beams were generated ranging from 15 MeV down to 220 keV; in addition two lower energy beams were used which consisted of a wide spectrum of energies and are described as file 110 and 60 keV spectra, which refers to their maximum values. High energy neutron beams were studied at the Texas A&M Variable Energy Cyclotron (TAMVEC) and the Naval Research Laboratory (NRL) Cyclotron situated in Washington, D.C. Both of these maclfines use the d-Be process and generate beams containing a wide spectrmn of neutron energies with maxima of 50 and 35 McV respectively.
INTRODUCTION THE RADIOBIOLOGICALproperties of neutrons are of interest from two points of view. First, such data contribute to our basic knowledge of the mechanism of radiation effects. Second, there is the more pragmatic reason that neutrons are being used increasingly in clinical radiotherapy as a result of the encouraging experiences reported from the Hammersmith Hospital. Two extensive series of experiments have previously been reported in which RBE and OER were studied as a function of neutron energy [1-3]. The present paper describes a new series of measurements that cover a much wider range of energies than has previously been possible. Using tile Radiotogical Research Accelerator Facility (RARAF) at Brookhaven National
METHODS Accepted 22 February 1974 *Based on work performed under Contract AT-(I I-1)3243 for the U.S. Atomic Energy Commission and Public Health Service Research Grant No. CA-12536 from the National Cancer Institute.
Two radiobiological ,test systems were utilized. Seedlings of Viola faba were ~sed to determine values for the OER and a/so to measure the RBE over the low dose range. 297
Eric J. Hall
298 Table I,
Characteristics of neutron beams studied
Average dose/rate Energy
Source TAMVEC NRL RARAF
Max. energy spread
Production process
For Vicia
For cells
50 MeV max. 35 MeV max. 15 MeV 6 MeV 2 McV 1 MeV 660 keV 440 keV
50-zero 35-zero _~4% • 7% + 5% _+11% + 13 + 22%
d--*Be d--+Be d-+T d---eD p-~T p-gI" p-~T p-+T
70 rad/min 50 rad/min 280 rad/hr 4-50 rad/hr 140 rad/hr 70 rad/hr --40 rad/hr
70 rad/mln 50 rad/min 1000 rad/hr 475 rad/hr 450 rad/hr 625 rad/hr 500 rad/hr 300 rad]hr
350 keV
+ 28% -23% • 30% I I 0-zero 60-zero
p--+T
30 radjhr
250 rad/hr
p-+T p-+T p-+T
16 rad/hr 35 rad/hr 15 rad/hr
130 rad/hr 85 rad/hr
220 keV I 10 keV spectrum 60 keV spectrum
The endpoint scored was growth inhibitlon of the primary root [4, 5], V79 Chinese hamster cells euhured in vitro was the test system of choice to determine RBE's over the higher dose range, and also to obtain information concerning the shape of the sm'viwd curves for different neutron energies. Methods of culture
have previously been reported in detail
[6].
Absolute dosimetry was performed using a 6 m m diameter spherical muhiplication ionization chamber constructed of tissue-equivalent plastic. T h e g a m m a ray contamination in the beam was measured with a calibrated Geiger-Mfiller dosimeter. A member of the R A R A F staffperformed all dosimetry measurements at both outside facilities, as well as at RARAF, using the same equipment.
....
~ 8o] ~-6o~ ~,*o! ~o: ~' to ~ ~ ao
~o
rrr,,,I
,
, ,2,p,,I
lypoxic. ,~,;, -T / r~.,-' ~ , -~ T./~~
~,~~ 1~ g~ g 4 , ,t..,d
,
a~"~. ~-"~.T I~
~ ,TItSM
~
VIG/A
~ rA
.
.on
r, I I - I l l R ]
.1
I
J,,
"1 /
l.d_l
RARAF
Ik
1 ,
, ,tHH~
TAI4VEO
I ilttta]
i
1
T
I,-IJ~ ''1
10
I
1 IJJ,,l~
100
NEUTRON ENERGY (MeV)
RESULTS AND DISCUSSION Figure 1 is a plot of the oxygen enhancement ratio as a function of nentron energy. There is a complex relationship between these quantities.
.,,-
,qARAV
tt .02
.......
i ~r rid .t
I
I0
TAtlVEC
i
i 100
NEUTRON ENERGY(~eV)
Fig. 1. OER as a function of neutron energy. The test system used was growth inhibition of Vicia ~eedlings. The closed circles represent data obtained with essentially monaenergetic neutron beams at the RadiologicalResearchAccelerator Facility and has previously been published [8]. The t~rtieal bars represent 95%-confidence intervals. The anchor and star representdata obtainedat NRL and TAMVEC with high aterg,y c),cIatronproduced neutrons of 35 and 50 MeV respectively,
Fig. 2, Upperpanel: The effective L E T as a funaion of neutron e~rg), calcufat~dfrom re]erodes]metricdata [7]. Middle proM: RBE as a function af neutron energy measured with Vicia seedlings under aerated and fOpoxia conditions [8]. Bottom panel: Correspondbagdata for mammalian cells ia culture.
A low O E R of about 1-3 is evident for neutron energies of 220-440 keV. As the neutron energy is increased the O E R rises to a m a x i m u m of 1.8 for 15 M e V neutrons. It has a somewhat lower value for the high energy cyclotron produced neutrons at T A M V E C a n d N R L , which is of considerable interest for radiotherapy, since sui:h beams already have the attractive properties of a high output and excellent depth dose characteristics, It must be emphasized that in the case of the high energy beams, a wide spectrum of neutron energies is involved and in Fig, t the O E R is plotted
RBE and OER Values as a Function of Neutron Energy against the modal energy. By contrast all but the two lowest energies at RARAF are monoenergetic. There is at least a suggestion that the OER rises again lbr the two lowest energy neutron beams utilized. Ttxe accuracy of the data is not sufficient for this to be argued M t h statistical validity, but the trend would be expected from a consideration of the spectra of recoil protons produced. Figure 2 is a plot of the RBE as a function of neutron energy. Included in t|fis plot are the data for Vicia seedlings under both aerated and hypoxlc conditions, as well as die corresponding data for Chinese hamster cells irradiated in viiro. Also shown are the theoretical predictions of effective LET made by Kellerer and Rossi
and based upon microdosimetric data [7]. The general shape of all tliese curves is similar, corresponding to a maximum RBE at a neutron energy of about 350 keV. The RBE's of the T A M V E C and NRL beams are higher than for 15 MeV monoenergetic neutrons. L,i both cases the beams include a wide range of neutron energies, and it is an arbitrary decision t o plot the RBE values against the modal energy.
Acknowledgements--The data summarized in this paper represent the team efforts of many individuals in tke Radlologieal Research Laboratory at Columbia University, and would not have been possible without the help and collaboration of the staffs of TAMVEC and the NRL cyclotrons.
REFERENCES I. 2.
3. 4. 5. 6. 7. 8.
299
R.J. BERRY, Hypoxic protection against fast neutrons of different energies-A review. Europ. J. Cancer 7, 145 (1971). G.W. BARENDSEg,Responses of cultured cells, tumours and normal tissues to radiations of different linear energy transfer. In Current Topics in Radiation Research, (Edited by M. EB~:RT and A. HOWARD), Vol. IV, p. 293. NorthHolland, Amsterdam (1968). G.W. Bar~NDSEN and J. J. BROt'mSE,Dependence of the oxygen effect on the energy of fast neutrons. Nalure, (Lond.) 212~ 722 (1966). E.J. HALL, The relative biological effectiveness of X-rays generated at 220 KVp and gamma rays from a cobalt-60 teletherapy unit. Brit. 3". Radiol. 34, 313 (1961). E . J . HALL and J. CAVANAC,H, The oxygen effect for acute and protracted radiation exposures measured with seedlings of I~Tciafaba. Brit. J. Radiol. 40, 128 (I967). E.J. HAI~L and S. LRHNERT, The biophysical properties of 3.9 GeV nitrogen ions. IV. OER and RBE determinations using cultured mammalian cells. Radiat. Res. (In press). A . M . KELLERER and H. H. Rosst, The theory of dual radiation action, in Current Topics in Radiation Research, (Edited by M. E~r.RT and A. HOWARD), Vol, 8, p. 85. North-Holland, Amsterdam, (t972). E.J. HALL, H. H. RossI, A. M. K~LLERER, L. GOODMANand S. MAmbO, Radioblologieal studies with monoenergetic neutrons. Radiat. Res. 54~ 431 (19%).
RBE and OER Values as a Function of Neutron Energy* ERIO J. HALL Radiologieal Research Laboratoo, , Department of Radiology. College of Physicians and Surgeons of Columbia University, New York, N.Y. 10032, U.S.A.
Abstract--A nao set of RBE and OER measurements are reportedfor ten neutron energies between 60 ke V and 15 Me V obtained at the Radiologieal Research Accelerator Facili O, at Bro&hav'ea National Laboratory. hi addition two higher energy neutron beams were studied at the Naval Research Laboratory in Washhtgton and at the Texas A & M Cyclotron. Two biological test systems were used, namely growth inhibition of Vicia seedlings and hamster cells cultured in vitro. In the ease of the OER, a minimum rathe of 1"3 was observedfor neutron energies of 220-4.40 kcV. OER increased with neutron energy to a maximum of 1.8for 15 MeV neutrons. A slightly lower value of 1.6 was found to apply to both of the high energy cyclotron-produced neutron beams currently being httroduced for radiotherapy. The plot of RBE as a fiuletion of twutron energy has a similar shape far both biological test systems employed; the maximum RBE occurs at a neutron energy of about 350 keV. The experimental data are consistent with the theoretical predictions made on the basis of mierodosimetrie measurements.
Laboratory, ten neutron energies have been studied ranging from 60 keV to 15 MeV. The characteristics of the beams used are summarized in Table 1. By using suitable targets essentially monoenergetic neutron beams were generated ranging from 15 MeV down to 220 keV; in addition two lower energy beams were used which consisted of a wide spectrum of energies and are described as file 110 and 60 keV spectra, which refers to their maximum values. High energy neutron beams were studied at the Texas A&M Variable Energy Cyclotron (TAMVEC) and the Naval Research Laboratory (NRL) Cyclotron situated in Washington, D.C. Both of these maclfines use the d-Be process and generate beams containing a wide spectrmn of neutron energies with maxima of 50 and 35 McV respectively.
INTRODUCTION THE RADIOBIOLOGICALproperties of neutrons are of interest from two points of view. First, such data contribute to our basic knowledge of the mechanism of radiation effects. Second, there is the more pragmatic reason that neutrons are being used increasingly in clinical radiotherapy as a result of the encouraging experiences reported from the Hammersmith Hospital. Two extensive series of experiments have previously been reported in which RBE and OER were studied as a function of neutron energy [1-3]. The present paper describes a new series of measurements that cover a much wider range of energies than has previously been possible. Using tile Radiotogical Research Accelerator Facility (RARAF) at Brookhaven National
METHODS Accepted 22 February 1974 *Based on work performed under Contract AT-(I I-1)3243 for the U.S. Atomic Energy Commission and Public Health Service Research Grant No. CA-12536 from the National Cancer Institute.
Two radiobiological ,test systems were utilized. Seedlings of Viola faba were ~sed to determine values for the OER and a/so to measure the RBE over the low dose range. 297
Eric J. Hall
298 Table I,
Characteristics of neutron beams studied
Average dose/rate Energy
Source TAMVEC NRL RARAF
Max. energy spread
Production process
For Vicia
For cells
50 MeV max. 35 MeV max. 15 MeV 6 MeV 2 McV 1 MeV 660 keV 440 keV
50-zero 35-zero _~4% • 7% + 5% _+11% + 13 + 22%
d--*Be d--+Be d-+T d---eD p-~T p-gI" p-~T p-+T
70 rad/min 50 rad/min 280 rad/hr 4-50 rad/hr 140 rad/hr 70 rad/hr --40 rad/hr
70 rad/mln 50 rad/min 1000 rad/hr 475 rad/hr 450 rad/hr 625 rad/hr 500 rad/hr 300 rad]hr
350 keV
+ 28% -23% • 30% I I 0-zero 60-zero
p--+T
30 radjhr
250 rad/hr
p-+T p-+T p-+T
16 rad/hr 35 rad/hr 15 rad/hr
130 rad/hr 85 rad/hr
220 keV I 10 keV spectrum 60 keV spectrum
The endpoint scored was growth inhibitlon of the primary root [4, 5], V79 Chinese hamster cells euhured in vitro was the test system of choice to determine RBE's over the higher dose range, and also to obtain information concerning the shape of the sm'viwd curves for different neutron energies. Methods of culture
have previously been reported in detail
[6].
Absolute dosimetry was performed using a 6 m m diameter spherical muhiplication ionization chamber constructed of tissue-equivalent plastic. T h e g a m m a ray contamination in the beam was measured with a calibrated Geiger-Mfiller dosimeter. A member of the R A R A F staffperformed all dosimetry measurements at both outside facilities, as well as at RARAF, using the same equipment.
....
~ 8o] ~-6o~ ~,*o! ~o: ~' to ~ ~ ao
~o
rrr,,,I
,
, ,2,p,,I
lypoxic. ,~,;, -T / r~.,-' ~ , -~ T./~~
~,~~ 1~ g~ g 4 , ,t..,d
,
a~"~. ~-"~.T I~
~ ,TItSM
~
VIG/A
~ rA
.
.on
r, I I - I l l R ]
.1
I
J,,
"1 /
l.d_l
RARAF
Ik
1 ,
, ,tHH~
TAI4VEO
I ilttta]
i
1
T
I,-IJ~ ''1
10
I
1 IJJ,,l~
100
NEUTRON ENERGY (MeV)
RESULTS AND DISCUSSION Figure 1 is a plot of the oxygen enhancement ratio as a function of nentron energy. There is a complex relationship between these quantities.
.,,-
,qARAV
tt .02
.......
i ~r rid .t
I
I0
TAtlVEC
i
i 100
NEUTRON ENERGY(~eV)
Fig. 1. OER as a function of neutron energy. The test system used was growth inhibition of Vicia ~eedlings. The closed circles represent data obtained with essentially monaenergetic neutron beams at the RadiologicalResearchAccelerator Facility and has previously been published [8]. The t~rtieal bars represent 95%-confidence intervals. The anchor and star representdata obtainedat NRL and TAMVEC with high aterg,y c),cIatronproduced neutrons of 35 and 50 MeV respectively,
Fig. 2, Upperpanel: The effective L E T as a funaion of neutron e~rg), calcufat~dfrom re]erodes]metricdata [7]. Middle proM: RBE as a function af neutron energy measured with Vicia seedlings under aerated and fOpoxia conditions [8]. Bottom panel: Correspondbagdata for mammalian cells ia culture.
A low O E R of about 1-3 is evident for neutron energies of 220-440 keV. As the neutron energy is increased the O E R rises to a m a x i m u m of 1.8 for 15 M e V neutrons. It has a somewhat lower value for the high energy cyclotron produced neutrons at T A M V E C a n d N R L , which is of considerable interest for radiotherapy, since sui:h beams already have the attractive properties of a high output and excellent depth dose characteristics, It must be emphasized that in the case of the high energy beams, a wide spectrum of neutron energies is involved and in Fig, t the O E R is plotted
RBE and OER Values as a Function of Neutron Energy against the modal energy. By contrast all but the two lowest energies at RARAF are monoenergetic. There is at least a suggestion that the OER rises again lbr the two lowest energy neutron beams utilized. Ttxe accuracy of the data is not sufficient for this to be argued M t h statistical validity, but the trend would be expected from a consideration of the spectra of recoil protons produced. Figure 2 is a plot of the RBE as a function of neutron energy. Included in t|fis plot are the data for Vicia seedlings under both aerated and hypoxlc conditions, as well as die corresponding data for Chinese hamster cells irradiated in viiro. Also shown are the theoretical predictions of effective LET made by Kellerer and Rossi
and based upon microdosimetric data [7]. The general shape of all tliese curves is similar, corresponding to a maximum RBE at a neutron energy of about 350 keV. The RBE's of the T A M V E C and NRL beams are higher than for 15 MeV monoenergetic neutrons. L,i both cases the beams include a wide range of neutron energies, and it is an arbitrary decision t o plot the RBE values against the modal energy.
Acknowledgements--The data summarized in this paper represent the team efforts of many individuals in tke Radlologieal Research Laboratory at Columbia University, and would not have been possible without the help and collaboration of the staffs of TAMVEC and the NRL cyclotrons.
REFERENCES I. 2.
3. 4. 5. 6. 7. 8.
299
R.J. BERRY, Hypoxic protection against fast neutrons of different energies-A review. Europ. J. Cancer 7, 145 (1971). G.W. BARENDSEg,Responses of cultured cells, tumours and normal tissues to radiations of different linear energy transfer. In Current Topics in Radiation Research, (Edited by M. EB~:RT and A. HOWARD), Vol. IV, p. 293. NorthHolland, Amsterdam (1968). G.W. Bar~NDSEN and J. J. BROt'mSE,Dependence of the oxygen effect on the energy of fast neutrons. Nalure, (Lond.) 212~ 722 (1966). E.J. HALL, The relative biological effectiveness of X-rays generated at 220 KVp and gamma rays from a cobalt-60 teletherapy unit. Brit. 3". Radiol. 34, 313 (1961). E . J . HALL and J. CAVANAC,H, The oxygen effect for acute and protracted radiation exposures measured with seedlings of I~Tciafaba. Brit. J. Radiol. 40, 128 (I967). E.J. HAI~L and S. LRHNERT, The biophysical properties of 3.9 GeV nitrogen ions. IV. OER and RBE determinations using cultured mammalian cells. Radiat. Res. (In press). A . M . KELLERER and H. H. Rosst, The theory of dual radiation action, in Current Topics in Radiation Research, (Edited by M. E~r.RT and A. HOWARD), Vol, 8, p. 85. North-Holland, Amsterdam, (t972). E.J. HALL, H. H. RossI, A. M. K~LLERER, L. GOODMANand S. MAmbO, Radioblologieal studies with monoenergetic neutrons. Radiat. Res. 54~ 431 (19%).