Nuclear Chemistry-State
of the Rrt for Teachers
Nuclear Medicine and Positron Emission Tomography: An Overview Timothy J. McCarthy, Sally W. Schwarz, and Michael J. Welch Mallinckrodt Institute of Radiology, Washington University Medical School, St. Louis, MO 63110 Nuclear Medicine General Nuclear Medicine Nuclear medicine is the field of medical practice that involves the oral or intravenous administration of radioactive materials for use in diagnosis and therapy. The majority of radiopharmaceuticals available (95%)are used for diagnostic purposes. These involve the determination of organ function, shape, or position from a n image of the radioactivity distribution within a n organ or a t a location within the bodv. After administration. the r a d i o ~ h a r rnaceutical locillizt!s within an organ or target tissue hue to its biolo~icalor ~ h s s i o l o a ~ characteristics c This dlannostic capability is us;aily theresult of the emission of gamma radiation from the radiopharmaceutical localized within a n organ. This allows for external detection and imaging using a special type of camera known as a gamma camera (Fig. 1). These cameras capture the radiation emissions using a sodium iodide crystal, which absorbs the gamma ray energy and produces scintillations. The crystal is linked to a photomultiplier tube, which multiplies the light response and generates a signal. This leads to a n output response relating the gamma energy emissions to their origin within the body. !Rvo types of display are available with the gamma camera. One is planar with the imaging plane parallel to the camera surface (Fig. 2). These images are ohtained after administration to visualize activity in the target tissue. Three-dimensional tomographic projections can also be obtained using computer-assisted reconstruction techniques.
sociated with such radiation. Before discussing the potentially harmful effects of radiation exposure it is important to note that humankind has always existed in a n environment that involves exposure to ionizing radiation. Natural background radiation includes terrestrial and cosmic radiation exposure and internal radioactivity deposited in the body due to naturally occumng radionuclides.
Natural Exposure The biological damage sustained by tissue due to ionizing radiation is expressed in terms of the tissue's equivalent dose measured in units of millisievert (mS) or millirems (mrem). This term becomes more meaningful if we think in terms of the background radiation exposure due to naturally occurring sources in the United States: approximately 3 mSv (300 mrem)/year ( I ) . The only other significant source of ionizing radiation to the US. general public is beneficial medical radiation. As a comparison to background radiation, the dose equivalent of a regular chest X-ray exam is about 0.1 mSv (about 10 mrem). Table 1 lists the average per capita radiation dose equivalent due to various sources. The component of the
Ionizing Radiation Historically, radiation has proven to be a valuable tool of modern medicine. The benefit to society is achieved with the recognition that there is a potential health hazard as-
Figure 1. A gamma camera is used in the majority of clinical nuclearmedicine imaging studies. The subject is positioned under the camera, and a radiopharmaceutical is injected through a vein.
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Journal of Chemical Education
Figure 2.Typical images obtained using a gamma camera using a technetium phosphate agent to delineate bone. Images taken from the front (left)and back (right) of the subject are shown. This patient has a tumor in the femur (shin).
Table 1. Annual Effective Dose Equivalent in the United States Population Source
Dose (mSv)
Table 3. Radlonuclide Generator-Systems Clinical Applications
% of Total
2.0 1.O 0.39 0.14 0.009 0.05-0.13
0.14 4 0.3 2.0
Nuclear Industry Weapons testing, research, etc. Rounded Totals
3.6
100
From lanmng radlatlon exposn of the pop" at on of me ,n 100 States. Nahonal Caunnl 01 Rad!abon Ponedm Remn no 93. Wash nalon. DC. 1987. NCRP Publlcatlons.
Table 2. Estimated Loss of Life Expectancy from Selected Health Risks Health Risk
6 2 ~ (Tin n 9.2 h)
-+
%U
(Tin 6 h)
" " ~ r (fin 13 sec) 6 8 ~(Tin a 68 min) " ~ b(Tin 78 sec) (Tin 9.8 min)
be considered in light of other health risks. One of the principal somatic effects attributed to low and moderate radiation exposure are cancers arising in a variety of organs and tissues. The American Cancer Society reports that approximately 25% of all adults 2 M 5 years of age will develop cancer a t some time due to all possible causes (5). The additional calculated risk of cancer induction due to low level radiation exposure is about 2 x 10-~/Sv.Thus, if each of the 10.000 U.S. nuclear-medicine workers received lo-' S t 1 rem) ofocrupatiunal exposure, the risk factor would predict only two additional cases of cancer annually This can be put in& perspective by looking a t other health risks and wmparing the relative "days of life lost" (Table 2) (6). Generator Systems
Estimated Days of Life Expectancy Lost
Smoking 20 cigarettes per day Overweight (by 20%) All accidents Auto accidents Alcohol consumption ( U S . average) Home accidents Drowning 10 mSv (1 rem)/yearfor 30 years All catastrophes (earthquakes,floods, etc.) l o mSv (I rem)/yearoccupational radiation dose equivalent --
" ~ r(Tin 25 days)
6 8 ~(Tin e 290 days)
55 27
Medical Diagnostic X-rays Radiopharmaceuticals Occupational Consumer products
""'Tc
" ~ b ( ~ 1 1 24.58 h)
Natural Sources Radon Other
+ + + +
9 g ~(Ttn 0 67 h)
Radionuclides with short half-lives are desirable for use in nuclear medicine; a short T,n allows administration of relatively large amounts of radioactivity with less resultant radiation dose to the patient due to rapid decay of the radionuclide. Additionally, the high photon yield of shortlived isotopes provides the high count rate necessary for high-resolution images. However, short-lived radionuclides present unique problems with distribution because they are often produced a t reactors or cyclotrons far from the medical center where they will be used.
-
From USNRC lnstr~n~on mncernlng nsr from OccJpatonal rao atton expow e Oran Regu aloly GL 0% Wash nglon DC. 1980,US Ndcear Commlsson
exposure due to occupational exposure of approximately 10.000 nuclear-medicme ~ersonnelin the L1.S. is a ~ ~ r o x i &ely 3 mSv (300 mremPyear, but averaged over the total U S . population, the average per capita dose is about 0.001 mSv of the total occupational exposure per year (2).
A Case Study Rosalyn S. Yalow, the Nobel Laureate, has discussed a study camed out in China to determine the effect of dose rates and doses comparable to background radiation (3). The study was camed out on a group of 150,000 Han peasants who had similar genetic background and lifestyle. One-half of the group lives in a region that received approximately three times more background radiation exposure. due to radioactive soil. than the other half of the group. The study looked at a number of possible radiationrelated health erects. The studv failed to find anv real difference between the two groups (4). Occupational Risk The risk involved in either nuclear-medicine procedures or occupational exposure for nuclear-medicine personnel must
I
!
0
,
, 10 20
, , , , , 30 40
50 00 70
, , , , ' 80 90 100 110 120
Time (hours) Figure 3. It is possibleto obtain a short-lived radionuclide by separating it from a long-lived parent. The most common generator system used in nuclear medicine is molybdenum-99ltechnetium-99m.The technetium "grows in" after a separation, with the maximum amount obtained approximately 22 h after separation. If all of the molybdenum decayed to technetium-99m, there would be more technetium than molybdenum present (x) after equilibrium. Because only 86% decays to technetium-99m, there is actually less technetium activity than molybdenum. Volume 71 Number 10 October 1994
831
Figure 5. The coincidence event described in Figure 4 is the basis of PET. Rings of detectors are placed around the subject, and each detector is placed in coincidence with many others. Thus, the exact distribution of radioactivity in the subject can be quantified.
Figure 4. Afier the decay of an atomic nucleus by positron emission, the positron travels a finite distance (a few millimeters depending upon the energy of the decay) and then interacts with an electron, thus undergoing annihilation. Then two 511-KeV photons are emitted at 180" to one another. By placing detectors at 180" and measuring events that occur within a short time frame, events in the cylinder joining the detectors can be determined. This problem has been solved by use of radionuclide generators, which consist of a long-lived parent radionuclide that decays to a short-lived daughter. Because the parent and dauahter nuclides are not isotopes of the same element, separation is possible. The long-lived parent can be used to generate a continuous supply of a relatively shortlived daughter. Many parentidaughter systems with these half-life characteristics are found in the periodic table. Several have been examined for clinical use (Table 3). The 99MoP9"Tc generator system is by far the one most commonly used in nuclear medicine. The daughter '""Tc has a Tvz of 6 h and a n optimum energy of 140 keV (90% abundance). A large number of radiopharmaceuticals are prepared with '""Tc. The parent radionuclide "Mo (Tm = 67 h) forms the anionic species molybdate (Moo4? and paramolybdate (Mo7OZa6)i n a n acidic medium. T h e molybdate anions are adsorbed onto the surface of an alumina column (A1203).The daughter "'"Tc is eluted a s the pertechnetate anion ([99mTclTc04Jfrom the generator with 0.9% NaC1. The "Mo remains bound to the alumina column because it is insoluble in the 0.9% NaCI. All generator systems reach a state of radioactive equilibrium after a certain length of time, depending on the half-lives of t h e p a r e n t and daughter isotopes. The 99"MoP9"Tc system reaches a state known a s transient equilibrium approximately 23 h after the generator has been eluted. At this point the amount of g9mTcpresent is 0.946 times the "Mo present because only 86% of the "Mo decays to ""Tc (Fig. 3). The physical properties of "'"Tc allow good imaging capabilities for use with the gamma camera and low radiation dose for the patients. Initial "'"Tc compounds were simple metal-chelates complexes such as the [""Tclpyrophosphoric acid ([99"TclPYP) (1)initially used for bone imaging. Over the years, more sophisticated "' Tc chemical compounds have been developed, such a s [""Tclsestamibi 832
Journal of Chemical Education
(2) and [99mTclteboroxime(31, which are radiopharmaceuticals used for cardiac imaging.
principle, the particle is introduced into a vacuum chamber within the cyclotron. The hollow D-shaped electrodes (Dees) accelerate the particles by being made alternately positive and negative. Magnets placed above and below the dees keep the particles moving in a spiral path until they are finally deflected out of the cyclotron and emerge to strike the target. Table 4 shows PET radioisotopes that are available from cyclotrons, with the half-life and nuclear reaction required to generate each isotope. A medium-sized cyclotron for production of radioisotopes suitable for PET costs around $2 million, and the system must be housed in a dedicated facility with large amounts of shielding. Due to the ultrashort half-lives of certain radionuclides, the cvclotron should he as close ns poshihle to the irnagtng I'W is limited at the pre. facility, so cscl~~tron-hnstd sent tb lar& medical institutions. Amore cost effective method for the production of the desired nuclides will help bring PET to smaller health care institutions.
Figure 6. A modern commercial PET scanner (photoprovided by Siemens) Positron Emission Tomography (PET) When a positron-emitting radionuclide decays, a positron (positive electron) is emitted from the nucleus. The positron then annihilates with a n electron, resulting in the release of energy in the form of two 511-KeV y-rays a t 180" to one another (Fig. 4). The energy of these photons is sufficient to pass through tissue. Thus, placing a series of detectors around the patient (Fig. 5) allows technicians to monitor the emission of both of the ~ h o t o n sthat result from a single positron annihilation. T&S ultimately allows an accurate auantification of the distribution of radioactivity in the body not possible when only a single y-ray is emitted. Figure 6 shows a photograph of a modern, commercial PET scanner.
Radionuclide Production The majority of radioisotopes used in PET (Table 4) are cyclotron-produced near or a t the site of the investigation. However, there are certain positron-emitting isotopes (e.g., copper-62) that are suited to generator-type systems (Table 3). In certain cases the half-life of the isotope is sufficiently long to allow transportation over a long distance from the production site. For example, copper-64 and iodine-123 have T m of 12 h a n d 13 h. The production of the short half-life positron-emitting radionuclides is achieved using a cyclotron (Fig. 7). This accelerates a charged particle (e.g., proton or deuteron), which is then collided into a target substance. This produces a nuclear reaction, furnishing the desired isotope. In
Rndem Cascade Accelerator One such alternative is the Tandem Cascade Accelerator (TCA) (Fig. 8), this machine generates the desired radionnclide by initially accelerating hydride or deuteride particles in an electrostatic tube. After obtaining 50% of the desired kinetic energy, the particles pass through a foil stripping assembly. The resultant proton or deuteron beam is then accelerated through a second electrostatic tube until colliding with the target a t the energy needed to furnish the desired radioisotope. The major design criteria for the cyclotron and TCA are compared in Table 5. As can be seen the TCA is considerably smaller and requires less shielding. Unlike the cyclotron, it does not need a dedicated power supply. These difTable 4. Radioisotopes for PET
Radionuclide
T~R
Nuclear Reaction
j50
2.07 min
14N(d,n)j50
' 3 ~
9.97 min
'%(p,a)13~
20.3 min
"C ' 8 ~
14~(~,u)"c
109.7 min
'80(p.ni'8~
9.8 min
%u
64~u
Generator 64~n(n,p)64~u
12 h
Table 5. Comparison of TCA with Medium-Energy PET Cyclotrons
TCA Energy
Figure 7. The biomedical cyclotron instalied at Washington University, St. Louis. The most common way to produce PETradionuclides in the hospital is using such a cyclotron.
PET Cyclotron
3.7 MeV prot
11-18MeV prot
3.7 MeV deut
7-9 MeV deut
Beam Current
750 PA
Floor Space Weight
240 f?
50 pA
,600 ?i
(accelerator only)
1 ton
25 tons
(shielding)
5 ton
20 tons
Power Consumption Volume 71
I2 kW
1OOkW
Number 10 October 1994
833
charcoal furnace a t 900 "C for 1l501CO and 400 "C for [l5O]CO2.The product gases have very high specific activi t and therefore can he administered by inhalation. The [' Olcarbonmonoxide binds to hemoglobin found in the red
K
a) [18qKF. MeCN. &,2,2 heat b) dilute HCI, heat
Figure 8. New compact accelerators are being developed to produce PET radionuclides. The Tandem Cascade Accelerator (TCA)is much more compact than the cyclotron; all power supplies and ancillary equipment are present in the accelerator room. This accelerator was developed by Science Research Lab (Somrnerville.MA) and is being commercialized by A.A.I.
Fi ure 10. The most commonly used PET radiopharmaceutical is [' F12-fluoro-2-deoxyglucose (FDG).This is produced by the chemi-
2
cal reaction shown
ferences are reflected directlv i n the cost of the TCA. which is currently estimated a t around $700,000, with iess expensive installation than a full-sized cyclotron. PET Radiopharmaceuticals
Many types of radiopharmaceuticals have been developed for PET, and they can be broadly divided into markers of perfusion, metabolism, and receptor density. The following section discusses each class and gives examples of the radiotracer synthesis and application.
Perfusion Agents From a historical perspective, perfusion tracers were among the first radiopharmaceuticals developed for PET. Perfusion can be further divided into the categories of blood flow and volume. Due to the ultrashort half-life compounds of oxygen-15, multiple doses can be administered over a short time. [1501carbon oxides can be produced by combusting the labeled gas ([15010-0) i n a n activated
hexakinase glucoseB-phosphate
-
2-FDG-6-phosphate
4 CO,
+ H,O
F gJre I 1 2-F ~oro-2-aeoxyg .cose s an ana ogLe of gl~coseWhen laken nto IassLe, lne fl.orog .cose s convencu nto Idorog Lose 6pnospnale, wh ch cannol be melabol zea f ~ n h ean0 r I n s s lrapped in the tissue. This allows retention of the tracer for imaging
Ftgure 9, Images in the brain activated when the subject hears, speaks, sees, and generates a word. (The subject generates a word when shown a noun and asked to associate a verb with it.) With a compound as simple as [ ' 5 0 ] ~the , ~function , of the brain can be studied. (Image couriesy of M. E. Raichle, Washington University School of Medicine; see ref 7). 834
Journal of Chemical Education
Figure 12. A tomographic section of a patient with a tumor (upper left) after administration of FDG. FDG also accumulates in the normal hean tissue as can be seen in the center of the image.
trapped in the cell because phosphorylation cannot proceed past the C-1 carbon (Fig. 11). In brain-imaging studies, FDG maps normal brain metabolic activity, whereas in cardiac studies, FDG is used to denote ischemic regions where glucose metabolism increases as a result of diminished fatty acid metaholism. Another important application for FDG is in the detection of tumors, due to the increased glucose metabolism (11) characteristic of tumor development and growth. AFDG PET image of a tumor is shown in Figure 12. Time of radiosynthesis:50 min The abnormal metabolic path1-[liC]-0-mannose wav of FDG can comoromise calFigure 13. Carbon-11 with its 20-min half-lifehas been used to label relatively complex molecules. For cuiations of tracer kketics when example, one carbon-11 deoxyglucose was synthesized by the reaction scheme shown. the biochemical fate of the radiolabeled metabolites is of interest. For studies of this type the ideal blood cells, allowing a measurement of red blood cell volradiotracer is [%ID-glucose. Early syntheses of ["Clgluume. cose involved the photosynthetic incorporation of ["CICOz Cerebral and myocardial blood flow is quantified by the into the light-starved leaves of swiss chard (12). This furuse of [1501Hz0;even such a simple compound can be used nished the desired radiotracer. However, because it is not in sophisticated biomedical studies. Raichle (7)has used radiolaheled a t any one carbon, there are problems with [1501Hz0to demonstrate that separate regions of the brain metabolic loss of the tracer at different rates for each posiare activated (Fie. tion in the molecule. However, the synthesis of [ " ~ j l - D .. 9) during various tasks (s~eakina - or reading words, etc.) by studying the differences in cerebral glucose has heen reported (13) and improved (14)(Fig. 13). blood flow.Aclever and raoid radiosvnthcsis of this can be This is an excellent example of the complexity that can be accomplished by b~bblin~'['~~]carbon dioxide through saachieved in the preparation of "C radiopharmaceuticals, line (8)(eq 1). especially when one considers that the half-life of this radiotracer is only 20 min. CO'~O+ Hz0 + H,CO~'~O-t ~ 2 ' 0+ CO, (1) Receptor-Based Radiopharmaceuticals The carbonic acid produced immediately undergoes isotopic exchange to furnish radiochemically pure [l501Hz0, Many biochemicals and drugs cause highly specific in-a stable fo-rm ready for inchanges in the body when &en in relatively small doses travenous injection. (15).kvidence from a variety of sources suggests that the Tracers for cerebral and primary event in the action of many peptide and steroid .. . myocardial perfusion have hormones and drugs is binding to a specific site on the not been limited to the complasma membrane or in the cytosol. Proteins that mediate pounds labeled with oxygenihe specific interaction are called receptors. 15 described above. Other raDue to the very short half-lives of the radioisotopes used diotracers have been in PET, it is possible to synthesize radiopharmaceuticals described including [l3N1amthat are not contaminated with the corresponding nonramonia and more complicated dioactive substrate. This is important for radiopharmaceucopper-chelated complexes, ticals that are designed to interact with receptors because such as [62CulPTSM(4) (9). the material administered is not present in a large enough concentration to perturb the system biochemically. In Metabolism Agents other words, the receptors are not saturated. Molecular oxygen metabolism can be readily studied usSteroid Receptors ing ['50]02. The metabolism of radiolabeled derivatives of glucose have attracted considerable interest. [18F12-deoxyKatzenellenbogen (16) has developed steroid radiophar2-fluoro-D-glucose(FDG) ( 5 ) is the most widely used fluomaceuticals as agents to evaluate receptor-positive tumors rine-18 radiotracer for PET. I t is readily produced (Fig. 10) of the hreast (estrogens and progestins), ovary (estrogens), via the nucleophilic displacement (10)of the commercially and prostate (androgens) in terms of prognosis for therapy and to image steroid-hormonereceptors. Good results have available triflate by ['8Flpotassium fluoride in the presbeen obtained for the estrogens. A fluorinated analogue of ence of the cryptand, kryptofix[2.2.2]. After hydrolysis of estradiol, 16a-fluoro-17P-estradiol (61, was synthesized the ketal-protecting groups, the [l8F1FDG is purified via and found to have binding properties similar to that of the ion-exchange chromatography and compounded for injection. This procedure has been automated using robots that facilitate the routine production of the radiotracer and also reduce the exposure of personnel to the radioactivity. FDG is used predominantly in the study of cerebral and myocardial metabolism. In the brain, FDG undergoes carrier-mediated uptake as a glucose analog and serves as a substrate for hexokinase. Due to the structural differences from the parent molecule (glucose), FDG is metabolically ~
~~
~
-
7
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Number 10 October 1994
835
such a s enzyme biodistribution and kinetics. Through the labeling of antibodies, the binding to antigens can be measured, allowing for the examination of potential tumor uptake. This has been investigated clinically using the anticolorectal carcinoma monoclonal antibody 1A3, which has been radiolabeled (18)with copper-64 via the bifunctional chelator BAT. Conclusion Nuclear medicine involves many branches of chemistry. Nuclear chemistry has developed accelerators and methods of radioisotope production. Inorganic chemistry h a s furnished t h e technology required for metalbased radiopharmaceuticals and organic chemistry for radiosyntheses involving fluorine-18 and carbon-11. Biochemistry gives insight into the uptake and metabolism of t h e s e radiotracers. Pharmacists are also a n important part of this field because the radiopharmaceuticals produced Figure 14. Receptor imaging of tumors is being carried out using several agents. Shown is an image of a r e categorized a s drugs. The an estrogen-receptor-positive breast tumor imaged using ['8~16a-fluoroestradiol.In this tomographic combination of this interdisciplisection. onlv the primary breast tumor and the dome of the liver (steroids clear through the liver) are nary research has led to a mediobserved cal specialty; one in three U S . hospital patients are diagnosed using radioisotopes. estrogen receptor. A convenient and rapid radiosynthesis of the fluorine-18 radiolabeled compound was developed. Literature Cited Excellent PET images of human breast tumors and in1. National Council of Radiation Protection, Report number 94;NCRP Publications: volved auxiliary lymph nodes have been obtained (Fig. 14). Washington DC, 1987.
Other Receptor-Based Systems Other receptor systems studied with PET are the neuroreceptors (171, particularly the cerebral dopamine receptor. Many fluorine-18 and carbon-11 radiolabeled ligands for this receptor have been developed. Studies of dopamine D-2 receptors have used analogs of the butyrophenone This radiopharmaceutical has neuroleptic, spiperone (7). been used to probe cognitive disorders such a s Alzheimer's and Parkinson's disease.
2. National Covneil of Radiation Rotection, Report numher 93; NCRP Publications: Washington. DC, 1987. ~ ~01itrcs ~ ~ = n~ d ~ = ~,; t 3. yaiow, R. S. ID L o l u r v d ~ . d i m d i ~~ ~ t ~ ~science, M. E. Bums.. Ed.:. lawis Publishers: Chelsea..MI.. 1988: on 239-259. 4 H k ~ hBarkmound R.td~liml#& . c . ~ IGroup T1.m~Z ,em- 1980.P19 A 7 7 4 W 5 Am.,," c,.,,Sal"y.('onirr,an. o n d k ' n i . Ucu York 11:e li i ' i N##.l.nr K ~ ~ l l r li l( ' ~ m m # ~ . # i>hn l i Xcy.lor?r, < i . i d r \Vslhmmon DL'. 1% l 7 Km:hlz M F JrwntrTrAmemron 1 W . 5 8 64,lksncr M I Hatcnle. bl E ln.+.~\ r',ne.\f,nd \v I1 Fn.m..n N e x Y . r * . I V U , 8 Ue1.t >I .I .L.Ron J F .%rk.J 9 1 P n , Chrm 19B9.:.I l.l?l 1 C ~ c n . > Al .>ll'hia? L' J .Welch >I J \I&u,rc A H . P c r q D Frrnsn&-RA-
...
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.
LO. Kilhoum. M. R. Fluorine-I8 lo&linz of mdioohormocputieoia: National Aeademv: warhinkon, DC. 1990. InBrpost 11. Niewig,O.E.;Wong, W-H.:Singletary.S.E.;Hortobagyi,G.N.;Kim,E.E. Conmr:Fmm Biology to Thempy; SquaNni, F.; Bedacqua, G.; Conte. P. F.; Surbone, A, Eds.: The New York Academy of Sciences: New York, 1993: Vol.696, pp 6.. 7. 1 4.. W . .
Litto", J. F.: we1eh.M. J.R&f. R ~ s .1911,45.35. Shiue,C.-F, Wo1f.A. P J Lobel. Compound. Rodiopharm. 19&5.22,171-182. Dence, C. S.; Powers, W. J.; Welch, M. JAppl. Radiat. Isotopes 1889.44.971-980. . C., Ed.; CRC Re-: Boca ReerptorBinding Radiofrwers 81.I & II; Eckelman, W Raton, FL. 1982. 16. Kat~enellenbogen,J. A. In Rdiophormoceuflmls: Chomktw ond Phormomlogy; Nunn. A. D., Ed.; Marcel De!&er: New Y d , 1992:Vol.55, pp 297331. 17. Lhgatrom, B.; Hart%& P. InR~diiphiimimifIc1cIs:Chhmii1'y'~ndPhhhmhhlogy; Nunn. A. D., Ed.: Marcel Oekker: New York, 1992: Val. 55. 18. Anderson, C. J.; Connett, J. M.; Schwarz, S. W.: Rocque. P A : Ouo, L. W.; Philpott. G. W.:Zinn, K R.:Mearea, C. E:We1eh.M. J. J NveL M d 1932.33, 1685-1691. 12. 18. 14. 15.
Protein and Antibody Labeling Labeling a protein with a positron-emittingradionuclide allows direct monitoring of various biochemical processes
836
Journal of Chemical Education
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