Commentary HISTORY CORNER Hal Anger: Nuclear Medicine’s

NEWSLINE Quiet Genius

al Anger is one of those individuals who have made truly revolutionary contributions to nuclear medi- Hcine. As we continue to celebrate the SNM’s half- century anniversary, it seems an appropriate time to remind our colleagues of Anger’s work. Millions of patients all over the world have benefited from diagnosis and treatment that depended on the use of the Anger camera and the innova- tions made possible by its development. Yet many of our younger colleagues are unfamiliar with the story of its gen- esis and the ingenuity and dedication that Anger brought to this and other innovations in our field. Anger was born on May 24, 1920, in Denver, CO. His father was a first-generation German-American and his mother was Hal Anger in 1965 with the whole-body scintillation scanner at British-American. When he was 5 years old, his family moved the Donner Laboratory. The small holes in the foreground are to Long Beach, CA, where he entered the Long Beach pub- part of the collimator. From the collection of Henry N. Wagner, lic schools. Showing an early interest in electronics, he built Jr., MD. a television set from scratch while at Long Beach Junior College in the late 1930s––an impressive feat at a time when the technology was new. From Long Beach, he entered the engineering school of the University of California at Berke- ley, where he was inspired by J.V. Lebacqz, who was at work on a seminal text on pulse generators. Anger received his bach- elor’s degree in electrical engineering in 1943. During World War II, Anger was among those who worked to develop radar at Harvard's Radio Research Laboratory. Anger went to work in 1948 at the Donner Laboratory, part of the larger Berkeley Laboratory that had been founded by the Nobel laureate Ernest O. Lawrence in 1931. John H. Lawrence, Ernest’s brother, was head of the Donner Labora- Anger is known internationally for his achievements in imaging tory, and, like his staff members, was dedicated to finding new technology. This photo was taken at the Deutschen ways to apply radioisotopes in medical diagnosis and treat- Gesellschaft für Nuklearmedizin in 1966. From the collection of William G. Myers, MD. ment. Anger’s immediate boss was Cornelius (Toby) Tobias, one of the many Hungarian refugees who came to the United 40 years, and among his many accomplishments were the States in the pre-war years and who contributed so much to use of 11C in studies of oxygen deprivation in pilots and the the development of the radiation sciences. Tobias was a found- use of xenon gas as an anesthetic. Tobias is best known for ing member of the Donner Laboratory and pioneered the study his work in radiation therapy, using the fifth in a series of of the biologic effects of cosmic rays. At the lab, he worked cyclotrons engineered by Ernest Lawrence. It was to this 184- with Luis Alvarez and Emilio Segré, who would also become inch cyclotron that Anger was assigned as an engineer. Nobel laureates. Tobias’s career at the lab spanned more than Among the first projects Tobias assigned to his new employee was modification of the 184-inch cyclotron so that The monthly excerpts from past years of SNM it could be used for irradiation of pituitary tumors with high- annual Highlights Lectures do not appear in energy deuterons. The cyclotron had been converted during Newsline this month so that this well-deserved trib- World War II to a large-scale spectrograph (or “calutron”) ute could be published. The Highlights feature will for the production of 235U for the first atomic bomb. After a resume next month with excerpts from 1986. mass spectrograph was built in Oak Ridge (TN) to produce

26N THE JOURNAL OF NUCLEAR MEDICINE • Vol. 44 • No. 11 • November 2003 28N NEWSLINE Commentary tons from the University towork ofChicago totheDonnerLaboratory commercialsuccess. on tomeetwithgreat (at first only patientswho hadreceived(at first therapeuticdosesof the smalldetectorsizeandrelatively poordetectionefficiency American Medical Association. Despiteearly problems with annual meetingandlaterthatyear atthemeetingof hisname. wasThe instrument exhibited atthe1958SNM by #3011057 onthescintillationcamerathatwould beknown released therightsto Anger, who, in1958obtainedU.S. patent rights. With helpfrom Tobias andJohn Lawrence, the AEC Commission (AEC),sothattheinventor couldseekpatent lab couldgettheinvention releasedfromthe Atomic Energy immediately notedthatitwould beto Anger’s advantage ifthe directortoseethenewthe laboratory invention. Lawrence ously O. hadlittlecontactwithErnest Lawrence, Tobias brought with 7photomultipliertubes. Although Anger hadprevi- 4inchesindiameter,a sodiumiodidecrystal optically coupled tion Laboratory, Publication 3653,1957). This cameraused ray emitters”(Berkeley, CA:University Radia- ofCalifornia entitled“Ain anarticle new formappinggamma- instrument Publication 2524,1954). (Berkeley, CA:University RadiationLaboratory, ofCalifornia The apparatuswas developed in1954 further, asreported lium-activated thatwas sodiumiodidecrystal 5/6-inchthick. paperwithapinholecollimatorinfrontofthal- graphic skin were usedtoproduceimagesonalarge pieceofphoto- 131 a tumorusing in 1952ontheuseofapinholecameraforvivo studiesof areas atthesametime. a device that couldsimultaneously recordemissionsfromlarge the restofemissionswere “wasted.” Anger setoutto develop under themoving scannercouldbedetectedatany given time; the patient’s bodywas aseriouslimitation.Only photonsdirectly movement over radiationdetectorbackandforth ofthecrystal nia atLos Angeles. Anger recognized thatthemechanical Cassen, chiefofmedicalphysics attheUniversity ofCalifor- news oftheinvention oftherectilinearscannerby Benedict inradiationchemistry.used instruments 1951;22:912–914). Well counterssoonbecamethemostwidely uids placedinsmallglassvials( around awell-like toassay compartment radioactivity inliq- counter in1950. The device arranged usedanthracenecrystals and nuclearmedicinewas theinvention ofaworkable well of contrastagentsforcholecystography. Anger alsoworked briefly with Alvarez onthedevelopment Inadditiontoengineeringthismodification, ical purposes. the Berkeley forbiologic cyclotron andmed- was reconfigured uraniumandplutoniumisotopes, large amountsoffissionable I couldbeimaged),theinvention was well received and went T When Alexander Gottschalk was sentby at Paul Harper The first Anger scintillationcamerawasThe first describedin1957 The first gamma camera report by gammacamerareport Anger wasThe first published 1951issueofthejournal The January of Anger’sThe first majorcontributionstobiochemistry HE J UNLOF OURNAL 131 I inapatientwithmetastaticcancernearthe 131 I ( Nature N UCLEAR . 1952;170:200–201).Gammapho- M EDICINE (Continued onpage 34N) Rev SciInstrum. Nucleonics • Vol. 44•No.11 •November 2003 carried clides suchas point was not sharedby otherscientists,and for administrationtopatients.” Fortunately, thisview- the chemicalelutionofageneratorinpreparingdoses meeting in1960that“hospitalswillnever undertake companiesstatedatascientific radiopharmaceutical The Importance of The Importance elution fromthe human body;and(c)Itwas readily available by Its 160-keV photonemissionwas suitable forthe advantageimportant forthescintillationcamera;(b) administered safely inlarge doses,anextremely radioactive which meant thatitcouldbe particles, al ucs fteAgrCamera Early SuccessoftheAnger cesses ofnuclearmedicinepractice. wide commercialsuc- became oneofthefirst stantial delays, thecamerawent intoproductionand work with Anger tobuildthecamera. After sub- Kuranz’s employee, Edward Reible, was assignedto president ofNuclearChicago,anew business. was tobebuiltundertheleadershipofJohn Kuranz, commercial version ofthescintillationcamera. This Medicine atOhioState,toplaceanorderforthefirst ofInternal Charles Doan,headoftheDepartment era andbecameitsstrongestproponent.Hepersuaded oftheinventionimportance ofthescintillationcam- ers inbiomedicine.Herecognized immediately the todirectacourseintheuseofradioactivetory trac- He traveled every summertotheDonnerLabora- andnuclearphysician.before becominganinternist intheatomicbombtestingatBikini had participated as thesourceofpositron-emittingradiotracers.Myers the potentialroleofcyclotron inbiomedicine dent atOhioState,Myers’s doctoralthesiswas on cessors ashistorianoftheSNM. stu- As agraduate Myers ofOhioStateUniversity, oneofmy prede- Anger scintillationcamerawas thelate William G. imaging. was onitsway tobecomingaworkhorse ofnuclear tory theavailabilitytory of of thebulletinBrookhaven NationalLabora- onthecoverin 1960,StangandRichardsadvertised images withtheoriginal Anger camera.Fortunately, metastable, decaying to that were idealfornuclearimaging:(a)Itwas recognized that generator. attheUniversity Paul Harper ofChicago The limitednumberofphotonsfromradionu- Another key personinthe development ofthe At theOakRidgeLaboratory, of3major officials 131 99m 99 I did not produce very impressiveI didnotproducevery Mo generator. Tc hadphysical characteristics 99m Tc, obtainable froma Henry N. Wagner, Jr., MD 99 99m Tc withoutemitting Tc andthe SNM Historian 99m 99 Mo Tc Hal Anger (Continued from page 28N)

with the new Anger camera in July 1962, he immediately rec- and Gottschalk had modified the camera with focused colli- ognized the importance of Anger’s work. In 1963, the 2 mation rectilinear scanning to provide the first instrument researchers described the localization of brain tumors with capable of producing multiple images focused at different the “positron scintillation camera” (J Nucl Med. depths from a single scan of a patient. 1963;4:326–330). This represented the first clinical use of the In recognition of his work, Anger received a Guggenheim positron scintillation camera and was an extension of the cam- fellowship in 1965 to extend his research efforts. After a era with an instrument that Anger had described in 1958 (Rev long and fruitful tenure at the Berkeley laboratory, Anger Sci Inst. 1958;29:2733). Gottschalk arranged for Anger to retired in 1982. He published more than 90 journal articles, move the new device to the Alta Bates Hospital in Berkeley, 22 book chapters, and held 14 U.S. patents during his career. where patients with brain tumors could be imaged. His accomplishments have been recognized with numerous The radionuclide used by Anger and Gottschalk was the awards and honors, including the 1991 von Hevesy Prize from positron-emitting 68Ga, with a half-life of 68 minutes. This the Georg von Hevesy Foundation, based in Zurich, Switzer- nuclide was obtained by elution from a germanium–gallium land. In 1994, he was the first person to receive the SNM Edu- generator system. The chemist at Donner, Yukio Yano, carried cation and Research Foundation’s Cassen Prize for distin- out the preparation of the 68Ga tracer. The new camera had guished achievement in nuclear medicine. He continues to an 11.5-inch diameter sodium iodide crystal, which made it live in California, where he pursues a lifelong interest in possible to examine the entire brain. Anger and Gottschalk studied 25 patients and compared the results with those photography. from the 203Hg-neohydrin rectilinear scanner images. Anger’s contributions to nuclear medicine––and the effects At the annual meeting of the SNM in Berkeley in 1964, these had on the subsequent technical direction of the Anger and Gottschalk presented a talk on the diagnostic appli- field––cannot be summarized in the limited space available cations of the scintillation camera, using 203Hg-neohydrin and here. Many innovations still under development depend heav- 131I-hippuran. Anger also collaborated with another Donner ily on insights and innovations that Anger brought to the field physician, Donald Van Dyke, in applying positron-emitting more than 50 years ago. It is clear that the nature of 21st- 52Fe to the use of the camera in imaging the distribution of century nuclear medicine has been profoundly affected by this iron in the bone marrow of patients with hematologic disor- unassuming, original, and inventive individual. ders and Paget’s disease. The results of this work were also Henry N. Wagner, Jr., MD presented at the 1964 SNM annual meeting. By 1965, Anger SNM Historian

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