Research Availability in North America

Inadequate North American supplies of research Mounting pressures to reduce government spend- limit research opportunities for ing, however, have created a crisis in the North radiochemists and other inves American supply of radionuclides. The current avail tigators in the United States and Canada. If basic ability of research radionuclides often fails to meet and clinical scientists lose confidence in the long- the needs of researchers. This failure results from term domestic availability of research radionuclides, intermittent production schedules and very limited resources devoted to production of "new" radionu the future practice of nuclear medicine may never realize its full potential for diagnosing and treating clides for pilot studies. Programs to secure ade disease with radiolabeled compounds that target quate, stable sources of research radionuclides specific molecular sites. Since the "Atoms for Peace" are not in place, a problem made more acute by the effort in the 1950s, the U.S. government has funded aging of national laboratory facilities with limited the production of investigational that are efforts to renovate or rebuild. Because the DOE not available from commercial suppliers. The facilities involved in radionuclide distribution pro U.S. Department of Energy (DOE) plays a vital role duce materials only in a "parasitic" operating mode, in funding the production of such radionuclides the future of such operations is inextricably linked in research reactors and accelerators, as did its pre to the ongoing viability of very expensive scientific decessor federal agencies (the Atomic Energy Com programs, such as high-energy physics research, mission and Energy Research and Development that are largely unrelated to biomédicalresearch. Agency). The supply of radionuclides to the nuclear medi-

Table 1 U.S. REACTORS AVAILABLE FOR PRODUCING RESEARCH RADIONUCLIDES

Maximum Flux Energy (N/cmVsec) Produces Reactor, Location (MW) Thermal Fast Isotopes for Comments

ATR National ixio15 5X1015 Commercial Main source of DOE-supplied reac- Engineering Laboratory applications tor-produced radionuclides (60Co, primarily I92lr,153Gd,89Sr);no capabilities for production of short-lived radionu clides.

HFIR, Oak Ridge National 100 2.5 X1015 1.2 X1015 Research/ Research/commercial applications Laboratory commercial Major upgrades planned that would applications expand capacity for radionuclide pro duction; currently operates at 85 MW.

HFBR,BrookhavenNational 7.5X10'3to4.2X10'*10 does not produce radionu LaboratoryMURR, clidesbio-medicalfor sale; recently produced "7mSn,!53Sm,isotopes ("Sc, 64Cu, 199AU).Logged'¡»Os,198Au,

ofMissouri30University 4.5X1014Cflux X101*(flux since1977;>90°/oonline time trap)8X10'3(graphitereflector)3.8X10"to1.5X10'"1trap)6X10'2(graphitereflector)ResearchapplicationsprimarilyResearch/commercialapplicationsCurrentlyresearchreactorlargest university powerupgradein the U.S.; capable of to 25 to 30 MW.

The Fast-Flux Test Facility [FFTF) at Hanford National Laboratory may become available for radionuclide production if the DOE decides to reactivate 3H production.

ATR = Advanced Test Reactor; HFIR = high-flux reactor; HFBR = high-flux beam reactor; MURR = Missouri University .

Newsline 15N Table 2 Clearly, we will need a variety of radionuclides Shipments of Radionuclides from High-Flux Isotope Reactor with various physical and chemical properties to (Fiscal Year 1996) create the sophisticated radiopharmaceuticals of the future. As Wynn Volkert, PhD, Associate Radionuclide Activity Shipped Units Shipped Research Career Scientist, H.S. Truman Memorial Ci GBq VA Hospital, Professor of Radiology, University of i92|r63NÌ89Sr600,0001601.522,000,000600055 Missouri, Columbia noted in the workshop intro duction, the future of nuclear medicine depends on the long-term, uninterrupted availability of research

2°9PO 1.1 x 10-6 0.4 x 10-6 radionuclides on a routine basis at reasonable costs. If researchers lose confidence in the long-term 13* 500* 25 mg domestic availability of radionuclides, warned Volk 8000 300,000 470 g ert, they will not devote their careers to radiophar- 7 batches of solution maceutical chemistry, and they will not build 2 batches research programs to design the sophisticated mol 188\A//'88Re 1 generator ecular radiotracers that hold so much promise for 'Theoretical activity. the future practice of nuclear medicine.

Nuclear Reactors cine research community, therefore, has become Four reactors currently produce most of the If researchers untenably dependent on extrinsic federal programs research radionuclides used in North America (Table and funding priorities. 1).The DOE and the University of Missouri oper lose confi In response to this growing crisis, the DOE com ate these reactor facilities. dence in the missioned the Institute of Medicine (IOM), of the National Academy of Sciences, to undertake an DOE Facilities long-term intensive examination of radionuclide production The DOE operates several research reactors, and availability. In 1995, the IOM Committee on including: domestic BiomédicalIsotopes issued its report, which empha •Idaho National Engineering Laboratory, sized the need to establish a reliable domestic Advanced Test Reactor (ATR) routinely produces availability supply of both reactor- and accelerator-produced radionuclides, but primarily for commercial appli of radionu radionuclides for medical practice and bioméd cations. ical research (/). At this time, most of the recom •Oak Ridge National Laboratory (), clides, they mendations of this report, including final design High-Flux Isotope Reactor (HFIR) routinely pro and construction of the National BiomédicalTracer duces radionuclides for research (Table 2) and will not Facility (NBTF), have not been implemented. commercial applications. In the core's hydraulic The crisis in radionuclide availability coincides, tube facility, seven to nine targets can be irradi devote their ironically, with an era of unprecedented opportu ated for anywhere from a few seconds to the full careers to nities for developing disease-specific radiotracers 25-day cycle. that could lead to promising advancements in nuclear •Brookhaven National Laboratory (New York), radiophar- medicine. Scientists worldwide are designing and High-Flux Beam Reactor (HFBR) recently became evaluating radiolabeled biomolecules to target spe available for small-scale irradiations. As this reac maceutical cific receptors and other cellular sites such as tor operates, seven vertical thimbles can be deoxyribonucleic acid (DNA) (2). These "designer" accessed for the production of short-lived radionu chemistry. compounds serve as the foundation for novel radio- clides. pharmaceuticals that could develop into highly Owen W. Lowe, Associate Director for Isotope effective weapons against cancer and other diseases. Production and Distribution, Office of Nuclear The Society of Nuclear Medicine's Committee Energy, DOE, reported that each DOE reactor has on Isotope Availability held a workshop on June the capability to produce radionuclides that can 6,1996, to examine current radionuclide availability not be produced elsewhere. The DOE reactors, and to explore currently untapped sources of together with the University of Missouri's research radionuclides. This effort to find alterna research reactor (MURR), comprise most of the tive sources of research radionuclides in no way total production capability available in the United diminishes the need to implement the recommen States to provide reactor-based radionuclides. At dations of the IOM Committee on BiomédicalIso the Hanford National Laboratory ( topes. Rather, the workshop focused on ways inno- state), the Fast-Flux Test Facility (FFTF) may vatively to overcome problems resulting from delays become available for radionuclide production if in developing dedicated federal production facili the DOE decides to reactivate the reactor for tri ties, such as the proposed NBTF. tium [3H] production.

16N THEJOURNALOFNUCLEARMEDICINE. Vol. 38 •No. 7 •July 1997 University of Missouri Table 3 Z As recognized in the recent IOM report (/), the Shipments of Research Radionuclides from MURR m MURR Center provides an outstanding example of (July 1992 to June 1993) the role a university-based facility can play in meet g i/i ing national and international demands for research Radionuclide Activity Shipped r radionuclides. MURR, a 10-MW , Ci GBq has an annulus-pressure vessel with a central flux >32P>50 Ci Z trap and operates 155 hours (6.5 days) per week at 1850 GBq 19%355198Au<86Res'Cr169Ybio3pd3'Si55Fe166HO63|S|¡'77LUBOTITI153sm796059205060284014806973441791721157976545451295,000219,000187,000105,00054,60025,80012,70066306360426029302810201019901870m full power. Alan R. Ketring, PhD, Interim Scientific Director, MURR, Leader, Radiopharmaceuticals Group, University of Missouri, Columbia, reported that MURR, the largest university research reac tor in the U.S., has logged >90% online time since 1977 and is capable of a power upgrade to 25 to 30 MW. MURR serves as the primary non-DOE source of research radionuclides in the U.S. (Table 3). The MURR Center believes it is capable of supplying North American researchers with adequate amounts of most short-lived (t Vi< 1 days), reactor-produced radionuclides "at a reasonable cost on a routine and reliable basis."

Nordion International Inc. Nordion International Inc., of Kanata, Ontario, Canada, operates its NRU reactor, which produces 1-50 Ci 191Os, «Ca, 75Se, "Mo, at Chalk River. Because of cost and logis 35-1850 GBq »«Sn, , '«Sb, tical issues, the NRU does not produce small 9?Zr, 153Gd, C, 188Re, 6*Cu, , 203Hg, amounts of research radionuclides. Ivan C. Tra vena, PhD, Vice President, Isotope Products, Nor dion International Inc., Kanata, Ontario, Canada, <1 Ci 13'Cs, 60Co, 133Ba, reported that the company is building two new < 35 GBq i«5Sm. 109Pd, 65Zn, '"-"Te, reactors Maple 1and Maple 2 to replace the NRU, 18273, 119mSn, n5Cd, 187W, '93mPt, 188W, scheduled to shut down in 1999. Maple 1(for rou 67Cu, 129Te, '»mje, le^Dy, "7Ca, 210ßj tine production) and Maple 2 (for backup pro duction) will be used to produce commercially MURR = Missouri University Research Reactor. viable radionuclides. Although ATR, HFIR, HFBR and MURR are all 2. Reba RC, ed. Molecular nuclear medicine. capable of producing research radionuclides, there JNuclMed 1995;36:1S-30S. are several limitations. ATR, for example, produces radionuclides primarily for commercial applica —Linda E. Ketchum, MS tions. HFBR produces biomedicai research radionu Ketchum InfoMedia, New York, New York clides, but they are not for sale; instead, they are —MarkA. Green, PhD available only to DOE-affiliated investigators. Cur Department of Medicinal Chemistry and Molecular rently, only MURR and HFIR routinely supply Pharmacology, Purdue University, West Lafayette, research radionuclides to any qualified investiga Indiana tor, regardless of DOE affiliation. —SilviaS. Jurisson, PhD Department of Chemistry, University of Missouri, ACKNOWLEDGMENT Columbia, Missouri Supported by grant DE-FG02-96ER62215, allo cated from the Office of Health and Environmen For correspondence or reprints contact: Linda E. tal Research, U.S. Department of Energy, admin Ketchum, Ketchum InfoMedia, 208 East 51st istered by the Society of Nuclear Medicine. St.,#1750, New York,NY 10022-6501.

REFERENCES 1.Adelstein SJ, Manning FJ, eds. Isotopes for medicine and the life sciences. Washington: National Academy Press; 1995.

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