Back to the Moon with Nuclear Rockets

have very little radio-therapeutic value inthe absence of boron capture, fastneutronsources have a proven clinicalbenefit even without boron capture. Fastneutronradiation therapy was used as acancer treatment tool at Lawrence BerkeleyLaboratory as early as 1938, and hasdeveloped over the years so that there arenow about 10 fast-neutron sourcesaround the world. In the United States,these sources are located at the Universityof Washington (the preferred site forinitial clinical studies of BNCT-boostedtherapy for Stage III lung tumors), and inDetroit, at the Harper Grace Hospital.There are eight additional fast-neutrontherapy units located in Essen, Orleans,Brussels, and Nice in Europe; Chibam,Riyadh, and Seoul in Asia; and Capetownin Africa.Clinical fast-neutron accelerators aredesigned to provide neutrons in the 10to 100 MeV range—energy which cannotbe obtained from a fission-based nuclearreactor. These accelerators are generallydesigned to accelerate protons ordeuterons to high energy, and then havethem impact a solid target to generatethe high-energy neutrons.For clinical applications, fast-neutronradiotherapy has shown benefit for salivarygland (treatment of choice), prostrate(improvement over conventionalradiotherapy), and soft tissue sarcomas,along with a subset of non-small-celllung cancers,BNCT Computational DosimetryDelivering neutron radiotherapy effectivelyto the tumor depends upon theability to maximize the quantity of neutronsthat reach the boron agent, whichis localized at the tumor site on an optimizeddosing regimen. This is accomplishedthrough complex computer programming,such as that developed overthe past 10 years at Idaho National Engineeringand Environmental Laboratory(INEEL).Radiation transport and dose distributionanalysis for BNCT and for BNCTaugmentedfast-neutron therapy is morecomplex than for photon therapy or forstandard fast-neutron therapy. There areseveral different physical radiation dosecomponents associated with BNCT, eachof which has a characteristic spatial distributionand biological effect. Accordingly,many of the simplifying assumptionsthat would work well for radiationtransport calculations associated withphoton therapy—and to some extentfast-neutron therapy—are not approj riateforBNCT.Explicit three-dimensional calcu a-tions with a complete treatment of pa tidescattering are required, both for calculationof the various dose compone itswithin the treatment volume, as well asfor calculation of the dose compone itsin critical normal tissue structures.In BNCT, as in photon therapy andfast-neutron therapy, it is important toperform detailed planning calculationsin order to optimize the treatment oreach individual patient. The goal i< todeliver the highest possible therapeiticradiation dose to the target tissue,while maintaining the surround nghealthy tissue at or below tolerance InBNCT-enhanced fast-neutron thera )y,there is an even greater necessity r orcareful planning, because of the e-quirement that both the geometric; llytargeted fast neutron component of hetherapeutic dose, as well as the BNCTcomponent, be optimized to the extentpracticable.Without this software, the clinicians,(medical physicists and radiation once logists)could not perform the radiotheraDy.The individualized treatment plann ngstarts from medical images (magnetic esonanceimaging, MRI, and computerisedtomography, CT, scans), combining th ;setwo-dimensional images into a thr;edimensionalmodel, and then optimizingthe dose distribution of the multiple d ssecomponents in the patient.The INEEL treatment planning softwareis the de facto standard around theworld in all of the research institutionsinvolved in BNCT research.Boron Chemistry and BNCT AgentsBecause the BNC reaction is spec fiefor the boron-10 isotope (which occursnaturally in a 20 percent abundance , itis necessary to enrich BNCT agent: inthis isotope to the greatest extent cc m-mensurate with expense and the effic icyof the agent in question. Boron-10 th; t ismore than 95 percent isotopically pjreis commercially available from Eaj le-Picher in the form of boric at id,10 B(OH) 3 . The most well developedBNCT agents—BPA, BSH, and NT GB-10—are all derived from this source ofboron-10-enriched boric acid.As driven by the physics of boron r eutroncapture, the boron concentration inthe tumor must be at a minimum of approximately30 micrograms 10 B/gram oftissue (30 ppm) to provide a clinical benefitin tumor control. The boron compoundsshould exhibit low toxicity, selectivedistribution into tumors and awayfrom normal tissue, and should be retainedin the tumor mass at the time ofneutron irradiation.The Food and Drug Administrationhas recognized these unique requirementsby placing the approval processfor both the boron compound and theclinical neutron source in the Center forDrug Evaluation and Research (CDER),Division of Medical Imaging, Surgical,and Dental Drug Products, which is thedivision that approves the enhancementagents and contrast agents for CT andMRI studies.At this time, three boron-1 0-enrichedagents suitable for use in boron neutroncapture therapy are under development:L-p-dihydroxybory(phenylalanine (BPA),Na 2 B 12 H 11 SH (BSH), and Na 2 B 10 H 10 ,(Neutron Therapies' NT GB-10). Theboron agents used between 1950 and1965 were compounds of low boroncontent, such as boric acid, B(OH) 3 , andarylboronic acids, ArB(OH) 2 , where Aris an aryl group such as p-chlorophenyl.While today's NT GB-10 and BSH areboth polyhedral ions and contain 64 percentand 57 percent boron by weight, respectively,the arylboronic acid BPAcontains only 4.8 percent boron byweight.The boron agents that are of currentdevelopmental interest fall into two classifications:The first type are essentially nontoxic,very high in boron content, and do notcross the blood-brain barrier or the membranethat similarly protects the spinalcolumn. Such agents require little targetingspecificity other than some selectiveretention in tumors, because adjacentcritical tissues, such as the brain or spinalcolumn, are protected from collateraldamage by the barrier membranes thatexclude the boron compounds.The second type are of high-boron contentand are capable of providing 30 ppmof boron-10 by weight to the tumor, withhigh selectivity. Examples of this typewould be liposomes, which can haveboron agents encapsulated in the aqueouscore, or derivatives of boron agentsincorporated in the membrane structure.Newer agents based upon phosphate diestertrailers and equipped with structuralSPECIAL REPORT21 st CENTl RY Summer 1999 11