Interview with DR. Victor Bond

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INTERVIEW WITH VICTOR BOND - SYNOPSIS 4 . Other approaches to therapy using external neutron beams and stable isotopes that can be activated _in situ MIRD enterprise - he was enthusiastic The old work of Lee Farr with BNL Graphite Reactor Bill Bale's work at Rochester and Georgia Tech Uses of reactors and accelerators for nuclear medicine Tritium - HTO vs organically bound - not a good source of " l o w Carcinogenesis by tritium Genetic effects of internal emitters His years at NRDL - laboratory and field Experience with fallout and test problems Therapeutic removal of internal emitters Control of exposures at tests - practice of assuming control of external dose would assure internal dose was not significant 15. A bit on de minimus and probability of harm

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Brook haven Na tiu 11 a7La bora t o ry me discussion concerns mstly chapters 10 an? 20. What i s your opinion of the MIRC: enterprise ? I haven ' t been that directly associated with it,but I did look into it care - fully when it first started.I was very impressed with it.I knew the people jnvolved,and I did go over the earlier calculations. effort.I haven ' t followed it since. I have remarked that there are those that feel the MIRD systen was sm thing I thought i t wzs a first - rate m a t I ' v e said h htrcducing MIFD was in canparison to the old system. to aqrandize nuclear mdicine, and I'm interest& i n that because the remarks caw frm p p l e in nuclear medicine. any are sticking to the' classical system. mey 2on't Fant t o use the MIRD system. my, and not making an issue of it. I ' m just saying that there are people who think that approach tothe problen. Ididn ' t see the t, because I thought their ' s was a very defensible scientific I t was very overt recognition that it was important t o , balance the amount of information. you gain, medically, diagnostic ally,vi rs us the As far as I ' m concerned s m surprising results wn-e out of it. Frankly, of dividing the post-mr years into two eras in chapter 2O? h t e n t and the era of ever mre scanning and ever shorter half-life isotopes? e2rly dtys there w2s a lot of tel k ebout the potential of isotopes in aile we are on fEirly broad things, what did you think of my little gimnick The era of the therapeutic

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dcses t= taxic dcses that killed the therapeutic approaches, exre?: for specia'l Dc you agree with my statement that it was really the closeness of the cases such as 32P in ply q th mia vera and i&e for th}croid.. B3M>: Orto say it another way, the failure t o Ix able to l mali ze selectively in the tissue of interest. the target tissue in terms of wanting t o destroy that tissue and the limiting, if you will, normal tissues was too small. The therapeutic ratio was just too Another way would be t o say the ratio of doses between BOND: I looked at that but I didn ' t go over it in detail. is scxrekcdy with a different opinion, -viz: Did you have a chance to look at the section on worries about m a t I say there is pretty mch what is in the literature, unless there that the leukemia risk was not greater - in fact it might be even a little bit less - when the thyroid oblation was by radio iodine as compared with surgury. BOND: (bleep)...it ' s not terribly relevant to this bears on classical toxicology. W e l l , it is, because in my last chapter I'm qoing to talk about how a l l BOND: All right,then you should look into that because there is an increasing number of papers indicating. - i n non-cancer situations I believe - where the number of cancers induced by the treatmen: are not insignificant. of course, rule out the cmparative risk t h i n g - or cost-benefit thinc;. you ' ve got a very serious disease you are willing to risk the relatively small chance of a new mer. way - or fitted in we ii with what w2s beir.9 done inthe general zrez of chenical I do hcpe t o say something about the ways i n which this work led the

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I wantet toget some more opinions) is the immuno loci c approach that Bill6ale ard liv Spar ard others used. Firstly, I find l i t t l e literature except frm, those two people. BOND: That ' s right.As far as I ' m concerned Bill Bale was the high mogul in that. He's the guy who did the quantitative,careful work. I haven't heard anything on that recently at all. STANNARD: I went t o see Bill in Atlanta. He retired from Rochester and went t o Georgia Tech. 1 understand he died a b i t ago. - BOND: Ididn ' t know that. STANNARD: He came up witha sigmoid cancer,or somethingolike that. He'd been having G.I. problems for years. amount of attention in a number of areas. One o f them has to do with boronneutron capture therapy. That i s not directly irrelevant,but it is relevant in that you are using the immunological approach to localize the target element - isotope that is, boron, and then activate by external means. Bales work and has the advantage, of course,that you can then turn on and off the reaction that you want at will. You use non-radioactive materials and allow them to localize in the target, and then by external irradiation with neutrons you turn on o r off the reaction that - you want. You have control over it that you lacked w i t h an isotope....If you want anythin9 mre on that, while you are here, Ralph Fairchild is working directly in that. As with a number of things the mnoclonal approach is now receiving a f a i r I think its worth a reference without any mt said much in here about Lee F a n ' s approach using the old reactor. itas rea1 ly not radi Gi sotope toxicology. cverall appmach is far fran deaci. bmate. . . . %en they went beyond that. It wzsn't stopped until long after it became That reminds me.of another detailed question I wanted toask you. I have In a way it's related,but in other ways it is fairly remote from it. That The early experience w a s very unfor-

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evident it wasn ' t working - that ' s the criticism of it. Damage was done to patients, just as danage was done with the first external fast neutron radiations, beceuse radiobiology wasn ' tthet well understood. But Stone did turn it off pretty ez rly. This went on,unfortunately, longer thar, i t should have. That doesn ' tin any way conflict biith the idea of the basic approach - It is sound. t o be able to use non-radioactive materials,to localize in the target that you want to destroy, and then activate by external means. The possibility is there,with neutrons,it ' salso very much there with photon activation,as well. Ralph Fairchild and I have written papers on this for both photon activation and neutrons STANNARD: Do you have copies? BOND: In the medical department. (He placed a call to Fairchild) because I have described the uranium work in the chapter on uranium. and perseverance, toGet that program going. did it witha very logical approach, which unfortunately wasn't souid enough, but was of ablod brain bier with respect t o tumr as oppsed t o an active bari-ier'for normal tissues, with the idea then that the boron would go into the abnormal area of the brain and not the normal, and you would get your differential that way. bmed out that there w a s not enough of a differential on that basis alone. other things were that the physics W n ' twell enough understood includin~~the depth dose considerations, and also it wasn't well enough studied or appreciated - that even though YOU got this apparent difference in gross concentration between the tumor and the norm1tissue, when one was activating - atall times you had I t has many attractions ; Yes. Why don ' t you see Ralph and get the latest ..... To be consistent I perhaps should say something about the boron work I think that Farr deserves alot of credit. It tmk a lot of innovation, It was not a sinple thing t o do. H e What wzs depended upon, initially, was simply the presumed lac k-

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therefore YOU2re deliver in s equal doses to the al j a cec ; blood vessels 2s you were inthe tumor. The net result was you didn ' t get the advantage. ... STANNARD: The medical reactor has 2 negtron bean that would work well ? BOND : I t was designed for that and its ideal forit. %e *&yes men't anywhere near being developd i n the perid we =e talking b u t . &, that was very recent - a very f e w years ago. It wasn't even heard of. STANNARD: Bill was working a t Georgia Tech on a similar approach. He was working a t the reactor thererand he was using microspheres which he could coat with anti- beam -es,and they wuld seek a given area, and then he would activate them with exte?rnalA BOND : I t ' s the same idea,but there again, he couldn ' t have anywhere near the specificity possible with mn0chrana.l antikcdies. SANEARD: He tried to change the specificity by manipulating both the antmy and the particle size. Another jen era l question - the uses of reactors in nuclear medicine. We've discussed the ideas for a neutron beam, but n m mst of the new approaches seem to be to make short-lived isotopes. developrrent Itloving in that 6irection or is there just a l o t m r e diacpostic work that use?, iSOMFeS that can ke produced with a reactor. d-xxt-lived isotopes that are mst useful are neutron deficient, and they are produced by accelerators,particularly hi ah energy accelerators. lzen toward the use of accelerator beams, such = the 200 Wv injector for the big cyclotron - the big syncrotron. There you take the beam that isn ' t used for the acceleration, and instead of dumping it someplace,you just put it in the CO you think there w i l l be any new reactors for neutron beams? Icarl ' t really see it for that purpose. There are, of course, medically .Ha ever, by and laqe, the The trend has - scl ut ions co ntz in in a the isotopes you want and you reap the short - lived isotopes many of which ars positron erni'rzers, I n many cases you get then i n much greater Furit?! ....... Kevertheless, I don't see any new reactors. If neutron

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captured therapy & a d d blossan, it's pssible. Hmver, there may be other cheaper rncdes o f prcducing suitable negtrons. I jus: don ' t see any further proliferation of nucleer reactors for this purpose. page 20.43 I discussed Brodsky's enthusim. for Johnson's paper that was given atthe oak Ridge Spp siu m. Earlier on, in Chapter 10, Isaid that tritium ss tri tia ted gas was probbly mng the mst benign of the radioisotopes - but that the situation was different when it was incorporated inthe nucleic acid precursors. I'd like to an-e back t o tritiated thymidine for a little bit. on I quoted this frcm Bray simply t o indicate how much concern for the additional effectiveness or the potential additional effectiveness was on people's minds. BOND: And notin the facts. t r i t i u m - God given to us - the safest nuclide t o use for these purpses", but further he says, "he always felt that tri tia ted thymidine was no mre than abut 100 times mre radiotoxic that HTO" You'll note that I have a fwtnote here that Brodsky not only says "Hail Iploted a footnote. I What Icm up w i t h later on is essentially the factors o u t of that NCRP camittee that Gene Cronkite chaired - which would make it in the order less that 1 0 , in many instances. Do you have a feel for what that factor ought t o be? in the right ballpark in your view? BOND: Yes, although I'm not sure I would put the emphasis i n the same pace.. What Imuld say is that i f you normalized the dose t o the nucleus,then it is not any That wzs the whole ppse of this pap here that you quote by Bond and That w z s the chief thing - that we used a numker of end points. And this is the f i r s t paper where across a nunhr of end pints it- normalizd t o dose tothe nuclevs. On th z tbz s is we found zero difference between the tritium i n thymidine or tri tia ted water. This w2s the first instance in which i t was stated overtly th z tits the dose tothe nuclegs that is important and compared then

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~e point that the number really varies on how you calculate it. B a classic, but I think mere in here I have mt i one d other ciassic papers This paper I regare BOND: Y e s . The ratio you are after, exactly as you indicated there, depends on the specific activity - on a number of factors, b u t i t ' s in the ballpark somewhere between 10 and 100. There again, in a way it is not tbe relevant grammar. That is in terms of exposure - of amount administered - and is n o t in terms of the actual effectiveness. Put it still another way - the reason for the perception of greater effect was the misconception t h a t because the isotope is actually lccalized h the Dm. that should then give you tremndously mre effect. it was never lake dat with that perception is that it originally excluded the DE4 Of course the reason and that doesn't necessarily equate a t all t o the mean energy to that tissue, i f would only expect that where there i s some sort of a transmutation .... SO y o u wouldn"t necessarily expect it to have any more effect, and you mt i f you do norndize t o dose then you can ' t find any added effect, as I wouldn't expert from the …