Heavy Charged Particle Beams Research Articles

Present and future proton treatment facilities at the Harvard Cyclotron Laboratory

The 160 MeV synchrocyclotron, built in 1948 for physics research, is currently the only facility in the United States which provides proton irradiation of malignant and non-malignant tumors. Starting in 1961 we have treated over 2600 patients, nearly 50% of all patients worldwide who have been treated with heavy charged particle beams. Irradiation of melanomas within the eye, for example, begun in July 1975, has been applied to 524 patients as of 30 June 1984. The number of patients treated has shown an exponential growth phase in response to the success of this method, followed by a leveling off as the facilities here have become saturated. This situation has motivated plans for a new proton synchrotron. Ideally such a machine would have a maximum beam energy of 250 MeV and be hospital-based. We estimate that a 70 MeV test model will take 3 years to build and will cost $1 million. Models of some machine components are already being built and tested at the HCL.

Hypoxic cell sensitizers and heavy charged particle beams may play complementary roles in killing hypoxic tumor cells

The analysis of growth delay data of a rat rhabdomyosarcoma tumor system with and without misonidazole and irradiated with spread-peak heavy-ion radiation yields two conclusions that bear on the relative efficacy of the two modes of treatment and imply a complementary role of the two modes which enhances the effects of either given separately. 1. For both carbon and neon ion peak radiation given in four fractions, RBE values for tumor growth delay are significantly greater than the enhancement ratio for an X ray plus misonidazole fractionation scheme (2.0–2.3 (carbon) and 2.6-2.8 (neon) vs. 1.2-1.5 (X rays plus misonidazole)]. This implies that high LET killing is considerably more effective in this tumor system (hypoxic fraction of about 3596) than the hypoxic cell sensitization caused by misonidazole. 2. When misonidazole is given in conjunction with the heavy ion beam irradiations, an increased growth delay is seen, greater than when either heavy ions or misonidazole plus X rays are given separately. The product of the sensitizer enhancement ratio for heavy ions and the RBE for no sensitizer yields a measure of the overall enhancement of effect relative to an X ray treatment. The values of this product for the carbon beam (2.4-2.5) and neon beam (3.4) show high effectiveness for either beam plus misonidazole. The interpretation is that heavy ion beams reach and kill hypoxic cells not penetrated by the misonidazole, and some hypoxic cells not killed by the high LET component receive low LET damage which is made lethal by the drug. Thus, the net hypoxic cell killing is enhanced by the high LET beams and in a complementary way by the combination of the drug and the low LET portion of the radiation.

The Changing Role of Accelerators in Radiation Therapy

Conventional low energy x-rays have been used in radiation therapy since the turn of the century. Van de Graaff and Betatron accelerators changed the complexion of radiation therapy in the mid 1940's by providing significantly deeper penetrating photon beams and also providing therapeutic quality electron beams. The development of Cobalt-60 teletherapy in the mid 1950's suppressed the role of accelerators in radiation therapy for nearly 20 years. However, with the development of reliable isocentric rotating linear accelerators, accelerators are rapidly becoming the most popular conventional therapy devices. Following unfavorable clinical results with fast neutron therapy in the late 1930's and early 1940's, the role of cyclotron produced fast neutrons is presently experiencing a renewal in radiation therapy. Several facilities are also experimenting with heavy charged particle beams for therapy. This changing role of accelerators in radiation therapy will be observed in detail along with a look to the future. I will concentrate on developments in North America. However developments in Europe closely parallel them.

Survival of Oxygenated and Hypoxic Tumor Cells in the Extended-Peak Regions of Heavy Charged-Particle Beams

The survival of oxygenated and hypoxic cells of the R-1 rat rhabdomyosarcoma tumor line in suspension culture has been measured at several positions in the plateau and the extended peak regions of carbon-, neon-, and argon-ion beams. Both the carbon and neon beams had 14- and 23-cm ranges in water; the argon beam has a 13-cm range. Peak regions extended to both 4 and 10 cm were studied for each ion species. In the 10-cm extended peak, OER values were close to 2.0 for the carbon-ion beam, 1.9-1.5 for the neon beam, and 1.4-1.2 for neutrons, while the argon OER in the extended peak is lower than that for neutrons. The RBE values increased through the carbon peak region, were large and relatively constant through the neon peak region, and decreased through the argon peak region, thus reflecting the changing effective LET that results from the changing energies and the different charges of the particles. An analysis of the effectiveness of the different ion beams for killing hypoxic cells in the peak relative to killing oxygenated cells in the plateau implies that, for single-port irradiations, carbon ions may be the most advantageous charged-particle species for the treatment of deep-seated hypoxicmore » tumors. However, for tumors at shallow depths, the present results indicate that carbon and neon ions are similar in their effectiveness. Argon ions may be superior for the treatment of poorly oxygenated tumors close to the body surface.« less

Current status of clinical particle radiotherapy at Lawrence Berkeley Laboratory.

Clinical experience with charged particle irradiation of human cancers has been underway at the University of California Lawrence Berkeley Laboratory. Over 150 patients have been irradiated with heavy charged particle beams including helium, carbon, neon, and argon ions. Pilot studies have included such tumor sites as glioma of the brain, carcinoma of the esophagus, carcinoma of the pancreas, carcinoma of the stomach, ocular melanoma, and carcinoma of the uterine cervix. Prospective studies are planned to investigate the improved dose localization potential (helium) and the enhanced biologic and physical dose potential (carbon, neon) in a controlled trial against the best available megavoltage irradiation techniques.

In Vivo Cell Survival and Volume Response Characteristics of Rat Rhabdomyosarcoma Tumors Irradiated in the Extended Peak Region of Carbon- and Neon-Ion Beams

Cell survival was measured for rat rhabdomyosarcoma R1 tumors irradiated in the distal 4-cm peak region of 400 MeV/u carbon- and neon-ion beams. An in vitro assay for clonogenic capacity was used to determine the surviing fraction of cells following in vivo tumor irradiation. Based on the response to 225-kV x rays under air-breathing and hypoxic conditions, it was estimated that the chronically hypoxic fraction of cells is 35%. From survival curves for tumors irradiated in air-breathing rats, RBE/sub 0/ /sub 1/ values determined at the 10% survival level were 2.0 and 3.1 for the peak carbon- and neon-ion radiation, respectively. Under hypoxic conditions, RBE/sub 0/ /sub 1/ values for peak carbon and neon ions were, respectively, 2.0 and 3.3 A diminshed oxygen effect was observed for the neon-ion relative to the carbon-ion radiation. Values of RBE for the two heavy charged-particle beams were also determined from measurements of tumor regression and regrowth following irradiation. Based on the ratio of x-ray to charged-particle doses required to produe a growth delay of 50 days, RBE/sub 50/ values for peak carbon and neon ions were 2.3 and 2.9, respectively. These RBE values are similar to those obtained in the cell survival studiesmore » and, to the extent that they reflect a large population of hypoxic cells, indicate that peak neon ions have a greater therapeutic potential than peak carbon ions for the treatment of radioresistant hypoxic tumors.« less

Visualization and Transport of Positron Emission from Proton Activation in vivo

Heavy charged particle beams can be widely used for cancer therapy if control in heterogeneous tissue is proved practical. A beam of protons at 200 million electron volts has been visualized in plastic and in a living animal by using an on-line positron camera. The fraction of the activity retained in the radiation site was found to be at least 70 percent of that produced in a dead animal. The sensitivity of the technique was established for a typical geometry.

Experimental tests of proton beam localization.

The depth of penetration of heavy charged-particle therapy beams is sensitive to the density of tissues traversed. Maximum depth of dose contours will vary appreciably as the beam passes through bone, muscle, lung, and air or gas. Calculations suggest that beam activation of the short-lived positron-emitting isotope 15O in vivo will permit localization of proton therapy beams with resonable detected-event density and dose. Preliminary tests of this method indicate that the beam can be located at depth with a typical dose of 15 rad, using a large field-of-view positron camera on-ling. This technique is also applicable to other heavy charged-particle beams, negative pions, and heavy ions.

Introduction to the use of protons and heavy ions in radiation therapy: Historical perspective

For over 20 years, medical irradiation using proton and subsequently helium ion beams has been utilized, principally for ablative therapy of the pituitary and most often with the plateau portion of the beam rather than the extended Bragg peak. More recently, cancer radiotherapy using proton beams has seen limited clinical trial in Sweden and more extensive ongoing trials in the Soviet Union.. Pilot studies of extended Bragg peak therapy of neoplastic disease using protons (Harvard cyclotron) and helium ions (184 in. Berkeley synchrocy-clotron) have been underway in this country for about one year. For ions heavier than helium, sufficiently penetrating beams for cancer radiotherapy became available August of 1974 with successful activation of the Bevalac at Berkeley. Extensive preclinical evaluation of the dosimetry and biological properties of these heavier ion beams are being directed toward an evaluation of their suitability for beginning clinical trials, with the latter planned for mid-1977 if results are favorable. Potential therapeutic advantages and the extent to which they are supported by present knowledge of the physical and biological characteristics of heavy charged particle beams will be discussed.

Pulsed Plasma and Low-Pressure Detonator Thrusters for Secondary Propulsion of Spacecraft

References 1 Perel, J. et al., Research and Development of a Particle Bipolar Thruster, AIAA Journal, Vol. 7, No. 3, March 1969, pp. 507-511. 2 Huberman, M. N. et al., Present Status of Colloid Microthruster Technology, Journal of Spacecraft and Rockets, Vol. 5, No. 11, Nov. 1968, pp. 1319-1324. 3 Burson, W. C., Research on Electrohydrodynamic Charged Droplet Beams, AFAPL-TR-67-199, Oct. 1967, Air Force Systems Command, Wright-Patterson Air Force Base, Ohio. 4 Stark, K. W. and Sherman, A., Research and Development in Needle and Slit Colloid Thrusters, TND-5305, Feb. 1970, NASA. 5 Hendricks, C. D., Research on High Intensity Charged Particle Sources, AFAPL-TR-67-92, Aug. 1967, Air Force Aero Propulsion Lab., Wright-Patterson Air Force Base, Ohio. 6 Pfeifer, R. J. and Hendricks, C. D., Charge to Mass Relationships for Electrohydrodynamically Sprayed Liquid Droplets, The Physics of Fluids, Vol. 10, No. 10, Oct. 1967, pp. 21492154. 7 Sherman, A., Parametric Analysis of Electrostatic Dispersion of a Liquid, X-734-67-321, July 1967, NASA. 8 Kidd, P. W., Parametric Studies with a Single Needle Colloid Thruster, Journal of Spacecraft and Rockets, Vol. 5, No. 9, Sept. 1968, pp. 1034-1039. 9 Perel, J., Yahiku, A. Y., and Mahoney, J. F., Focusing and Deflection of Heavy Charged Particle Beams, AIAA Paper 69-283, March 1969, Williamsburg, Va. 10 Perel, J., Mahoney, J. F., and Yahiku, A. Y., Analytical Study of Colloid Annular Thrusters, AIAA Paper 70-1113, Aug.Sept. 1970, Stanford, Calif.