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					      Posicam 6.5 BOO Positron Camera. J Nuc/Med l990;31:6l0—6l6.                 142. Hill JL, Gettes LS. Effect of acute coronary artery occlusion on local
 129. Raylman RR, Hutchins GD, Schwaiger M, Paradise AH. The effect of                   myocardial extracellular K+ activity in swine. Circulation l980;6l:768—
      axial sampling and motion on three-dimensional quantification of myo               777.
      cardial defects with positron emission tomography. J Nuc/Med l989;30:         143. Conrad GL, Rau EE, Shine KI. Creatine kinase release, potassium-42
      892.                                                                               content and mechanical performance in anoxic rabbit myocardium. J
 130. Bendriem B, Dewey SL, Schlyer Di. Dependence on the recovery coeffi                C/in          1
                                                                                               Invest979;64:l55—161.
      cient on axial sampling in multislice positron emission tomography. J         144. Gould KL, Haynie M, Hess Mi, Yoshida K, Mullani NA, Smalhing RW.
      Nuc/Med 1989;30:892.                                                               Myocardial metabolism of fluorodeoxyglucose compared to cell mem
 131. Gould KL, Goldstein PA, Mullani NA. Economic analysis of clinical                  brane integrity for the potassium analog Rb-82 for assessing viability and
      positron emission tomography ofthe heart with rubidium-82. JNucl Med               infarct size in man by PET. I NucI Med 1990:31:1—9.
       1989:30:707—717.                                                           145. Sease D, Garza D, Merhige ME, et al. Does myocardial uptake of F-18-
 132. Gould KL. Goals, gold standards and accuracy of non-invasive myocar                Fluoro-deoxy-glucose by positron emission tomography reliably indicate
      dial perfusion imaging for identifying and assessing severity of coronary          myocardial viability in acute myocardial infarction? [Abstract]. Circula
      artery disease. Current Opinion in Cardiology l989;4:834—844.                    tion l989;80:II—378.
 133. Gould KL, Mullani NA, Williams B. PET, PTCA and economic priorities.          146. Pierard LA, DeLandsheere CM, Berthe C, Rigo P. Kulbertus HE. Iden
      C/in Cardiol 1990:13:153—164.                                                    tification ofviable myocardium by echocardiography during dobutamine
 134. Bodenheimer MM, Banka VS. Fooshee C, Hermann GA, Helfant RH.                       infusion in patientswith myocardial infarction afterthrombolytic therapy:
      Relationship between regional myocardial perfusion and the presence,               comparison with positron emission tomography. J Am Coil Cardiol
      severity and reversibility of asynergy in patients with coronary heart              l990;l5: 102 1—31.
      disease. Circulation l978;58:789—878.                                       147. Bianco JA, Bakanauskas J, Carbon M, ci al. Augmented uptake of 2-C-
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      versible myocardial asynergy. Circulation 198 l;64:936—944.                 148. Komatsumoto 5, Greenberg JH, Hickey WF, Reivich M. Local cerebral
 136. Iskandrian AS, Hakki A-H, Kane SA, God IP, Mudth ED, Segal BL.                     glucose utilization in chronic middle cerebral artery occlusion in the cat.
      Rest and redistribution thallium-20l myocardial scintigraphy to predict            J Cereb Blood Flow Metab 1989;9:535—547.
      improvement in left ventricular function after coronary arterial bypass       149. Wijns W, Jacque AM, Leners N, et al. Accumulation of polymorphonu
      grafting.AmJCardio/      1983;Sl:l3l2—l3l6.                                      clearleukocytes in reperfused ischemic canine myocardium: relation with
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      in delayed thallium-20l single proton emission computed tomographic                Med l988;29:    1826—1832.
      (SPECT) images: an overestimation of myocardial scarring. J Am Coil           150. Mody F, Buxton D, Krivokapich J, Hansen H, Scm C, Schelbert H.
      Cardiol 1988;l2:955—963.                                                         Attenuated response ofglucose metabolism in reperfused canine myocar
 138. Galli M, Bencivelli W, Pardo NF, Tavazzi L Underestimation of residual             dium to changes in substrate levels. JAm Coil Cardiol l990;15:80A.
      ischemia by thallium-201 scintigraphy after myocardial infarction. Chest      151. Merhige ME, Ekes RD. Mossberg K, Taegtmeyer HT, Gould KL. Cate
       1988;94:876—878.                                                                chol stimulation, substrate competition and myocardial glucose uptake
 139. Tamaki N, Yonekura Y, Yamashita K, et al. Relation ofleft ventricular              in conscious dogs assessed with positron emission tomography. Circ Res
      perfusion and wall motion with metabolic activity in persistent defects on          l987;6l(supp II):l24—l20.
              tomography in healed myocardial infarction. Am J Cardiol
       @°‘T1                                                                     152. Bonow RO, Bacharach SL, Cuocolo A, Dilsizian V. Myocardial viability
       1988;62:202—208.                                                                in coronary artery disease and left ventricular dysfunction: thallium-20l
 140. Brunken RC, Kottou 5, NienaberCA, ci al. PETdetection ofviable tissue              reinjection vs fluorodeoxyglucose [Abstract]. Circulation l989;80: (suppl)
      in myocardial segments with persistent defects at Tl.20l SPECT. Ra                 11—377.
      diology l989;l72:65—73.                                                     153. Bonow RO, Dilsizian V, Cuocolo A, Bacharach SL. Myocardial viability
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EDITORIAL
The ClinicalRoleof PositronEmission          for
                                   Tomography Cardiology
in the 1990s and Beyond

A    lthough positron emission to                     required equipment ($5-7 million                         joint ventures between  clinicaland/or
       mography (PET) has been per                    with camera, cyclotron and support                       research centers with radiopharma
formedin patientsfor more than 15                     ing equipment), absence ofU.S. Food                      ceutical groups that share a cyclotron.
years, it has only recently begun to                  and Drug Administration (FDA) ap                         By sharing or leasing the cyclotron,
emerge as a diagnostic modality for                   proval, the lack of widespread reim                      the capital equipment and operating
use by clinicians. Implementation of                  bursementfrom federaland private                         costs should be reduced while making
clinicalPET hasbeendelayed sev   by                   insurers,and the paucity oflarge din                     PET tracers available to sites with
eral factors, including the high cost of              ical trials (including outcome data)                     cameras but without cyclotrons. The
                                                      from multiple sites. Some solutions to                   regulatory  barriersarealsostarting  to
                                                      these limitations appear to be near.                      resolve. In November           1989, the FDA
   ReceivedJan. 17, 1991.                                                                                       issued a position statement on PET
   For repnnts contact: Richard A. Goldstein, MD,
                                                      The entry of major manufacturers
Director, Nuclear Cardiology, Cardiology Division      into PET imaging should decrease the                     radiopharmaceuticals  indicatingthat
Room 1.246, The Lhiiversity of Texas Medical           price of cameras due to increased                        PET centerscould continue to operate
School at Houston, 6431 Fannin, Houston, TX
77030.                                                 competition.      Other recent changes are               eventhoughNew Drug Applications


606                                                                                         o         M       •       No.4 April
                                                                                   TheJournal f Nuclear edicine Vol.32 • • 1991
(NDAs) were not yet approved. Sub                           on
                                          extentof disease the basisof non         likely to increase the price of SPECT
sequently, rubidium-82 generator use                                      o
                                          invasive,direct measurements f re        systems substantially.
for clinical purposes was approved in     gional perfusion at rest and during
December 1989. The issues related to      high flow states (exercise or pharma
reimbursement are now being re            cologic). This type of approach would    PerfusionImagingwith PET
viewed by the Office of Health Tech       be similar to the earlier animal exper
nology  Assessment  (OHTA) at Health      iments that formed the foundation for       Several investigators have devel
Care      Financial    Administration     defining severity of stenosis in terms   oped models with PET to measure
(HCFA) for Medicare coverage and          of anatomy   and physiologic   limita
                                                                                   regional perfusion in absolute terms
independently by members of Health       tionsin increasing  myocardialperfu       using rubidium-82, oxygen-l5-water,
Insurance Association of America         sion in response to stress.               and nitrogen-l3-ammonia(17—19).
(HIAA). This editorial reviews the ad                                              However, coronary blood flow esti
vantages and limitations of PET im                                                 mates by PET have not been directly
aging as a diagnostic modality and       PerfusionImagingwith Single-Pho                      to
                                                                                   compared anatomicmeasurements
discusses whether these enhancements       Emitters
                                         ton                                       of stenosis severity obtained with
justify the higher cost of equipment
                                                                                   quantitative arteriography (QCA).
and ensuing charges for clinical stud        Myocardial perfusion imaging with Relative perfusion reserve (stress to
ies.                                                                           as
                                          thallium-20l is well established a rest in a defect divided by a compa
                                          meansfor diagnosing        coronaryheart rable measure for a normal segment)
                                          disease (6—10). Initial studies showed  has been studied in patients who have
PHYSIOLOGIC ASSESSMENT OF a high sensitivity and specificity but undergone QCA (20). In these studies,
CORONARYHEART DISEASE                     more recently, the observed specificity relativeperfusion     reservewasnormal
                                                                       O
                                          has decreased (11—12). ne explana       until the stenosis exceeded 50% in
   The final arbitrator for the diagno                               is
                                          tion for thesechanges referralbias. diameter and then decreasedwith
sis of coronary disease has been the For example, if one begins to rely on more severestenosis. ollowingan   F
presence of a visually determined ste                            a
                                          a testfor decisions boutthe needfor gioplasty,                in
                                                                                               changes perfusion     reserve
nosisof >50% diameter narrowing arteriography, there is a bias to do parallelarteriographic hanges ste       c        in
based on coronary arteriography (1).      invasive testing only on abnormal nosis severity (21). These results are
                                                                                                 w
The use of arteriographyas the “goldthallium studies and not in patients concordant ith animalstudies                relat
standard― has recently been chal        with normal 201T1      scintigrams. Thus, ing anatomy and coronary flow re
lengedby severalinvestigators        that specificityfalls since patients with serve (22).
point out significant inter- and in       false-positives have arteriography,          Although  themeasurement     ofmyo
               v
traobserver ariability,the eccentric whereasmost patientswho are true cardial perfusion per se should theo
                                                      d
ity of most coronary lesions, and the negatives o not. The sameevolution retically improve our ability to assess
difficulty in relyingon percentnar would be expected for any test relying           coronary disease, it is important to
rowing when the “normal― of the on a binary decision (positive/nega
                              part                                                  the clinician and insurer to know
vessel, the denominator in percent tive).Thallium-201 is inherentlylim whether these differences will justify
narrowing, may itselfbe diffusely dis     ited to this type of analysis since the the attendant higher cost of PET by
                                                    o
eased (2-4). An additional problem absence fattenuationcorrection              pre reducing or eliminating more expen
with the use of a 50% stenosis as the cludes      truequantitationof activity.      sive procedures and/or decreasing
definition ofa significant coronary ar       Two new technetium-99m-based morbidityand mortality.When PET
tery lesion is the implication that pa    perfusion agents have recently been has been evaluatedusingsensitivity
tients with lesser degrees of stenosis approved by the FDA: teboroxime and specificity, the results have been
do nothavephysiologically     important (Cardiotec) and sestamibi (Cardiolite)      promising.
disease. The basis for the selection of (13—16). higher photon decay en
                                                     The                               In an early study, Schelbert re
a 50%diameter cutoffpoint is derived ergy of 99mTcshould decrease atten             ported a sensitivity of97% and a spec
from animal studies using fixed ste       uation artifacts. However, published ificity of 100% for PET stress perfu
nosis of variable severity (5). Lesions studies have not clearly demonstrated sion imaging with ‘3N-ammonia 32       in
with >50% stenosis are associated an improvement in diagnostic accu patients with disease and 13 controls
with a decrease in maximal flow with racy with thesetracers over that ob            (23). Similar results were obtained by
vasodilation (i.e., decreased coronary tamablewith 201T1.                           Yokenura et al. (24). Demer and col
flow reserve).Since the diagnosis of a       In theory, advances in camera tech leagues compared ‘3N-ammoniaor
functionally significant lesion is based nology might allow attenuation cor 82Rbrest/dipyridamole stressimages
on the inability to increase flow under   rection to be performed with SPECT to QCA and found a good correlation
stressconditions, it would seempref to obtaintruequantitation.However, between coronary flow reserve (CFR),
erableto determine the presenceand such technical improvements are estimated                                       a
                                                                                               fromarteriography ndvis


TheClinicalRoleof PositronEmissionTomography•
                                             GoldsteinandWilerson                                                    607
uallyinterpreted   PET (25). Recently,    abolicallyactive myocardiumtakes            of FDG uptake in such regions may
Go et al. compared thallium SPECT         up glucose. With myocardial ische           be facilitatedby the quantitative prop
and 82Rb PET directly to arteriog         mia, uptake of glucoseis enhanced           erties of PET imaging and the pres
raphy in 202 patients, 133 of whom        because of a diminished oxygen sup                       spot―
                                                                                      ence ofa “hot to readas opposed
had neither prior coronary artery by      ply that increases anaerobic metabo                   spot―or thallium.
                                                                                      to a “cold    f
pass procedures nor angioplasty (26).     lism.FDG isextracted   similarlyto its        Several other approaches to the
They reported a statistically signifi     normal     circulating   physiological      PET assessment of viability have
cant increase in the sensitivity of PET   counterpart. However, after it is phos      undergone      preliminary       testing,    in
of 95% (compared with 79% for             phorylated  and trappedin the cell, it      cluding the use of labeled fatty acids
SPECT) but no change in specificity       is not broken down further. Tillisch et     (carbon-l l-palmitate), aerobic me
(82% compared with 76% for PET       al. found that the presence of FDG in            tabolites (carbon-l 1-acetate and py
and SPECT,respectively).In contrast, myocardium, normalized for differ                ruvate) and differential      washout of ru
Stewart et al. from Michigan reportedences in delivery, predicted improve             bidium-82 (35—38). Further clinical
a higherspecificity  and similarsensiment in regional left ventricular func           validation of these tracers must be
tivity with PET/SPECT in patients    tion following surgical revasculariza            performed before they can be consid
compared   with quantitativecoronary tion. Patientswithout FDG uptake                 erableacceptable markersof viability
arteriography (27).                  had no significant change in wall mo             in patients.
                                          tion (29).   These observations     have
                                                                        for
                                          beenusedasa clinicalbasis differ
The Positionof PET Today                  entiating potentially reversible is FUTURE DIRECTIONS
                                          chemic disease(i.e., “hibernating―
   The major advantage of PET over                       f
                                          myocardium) romextensive       myocar       The quantitative properties of PET
SPECT is the ability to correct for       dial scarin patientswith severeleft      and the wide range of possible tracers
differences in attenuation that would     ventriculardysfunction who are being using carbon-l 1, nitrogen-13, and flu
be expected to improve interpretation     considered for coronary artery revas     orine-18 should expand the use of
by minimizing artifacts. Another ad       cularization procedures or cardiac PET as the technology becomes more
vantage  istheabilityto complete   stud   transplantation.                                            P
                                                                                   widelyavailable. ET should      beuseful
ies in 1—1.50r as opposed to 4—6r
              h                       h      Do 201T1  redistribution scans pro    asa research   andclinicaltoolforeval
for 20Tl and @mTc@sestamibi.       Does   vide similar information?Thallium uating interrelations             between hor
quantification  makea significant ifd     redistribution imagingfor viabilityis    monesand their receptors in theand
ference in selecting patients for inter   based on differences in flow-depend      determination    of cellular abnormali
vention? Theoretically it should.                                                                   w
                                          ent washout between normal, is tiesassociated ith the development
Given the variabilityof interpretation    chemicand infarctedregions      (30). In of cardiomyopathies, arrhythmias,
of arteriography and the attenuation      experimental animals, viability is usu   atherosclerosis, and thrombosis. An
problems  with 201Tland99mTc, isPET       ally presentin myocardium with flow other potential role for PET may be
a strongcandidate for use as a decision   greaterthan 0.6 ml/min/g and absent in theevaluation        ofunstablecoronary
end point for determining the need        in regions with flow less than 0.4 ml/   artery plaques and in identifying pro
for arteriography and whether a lesion    min/g (31). Regions with intermedi                 and               o
                                                                                   gression regression f atheroscle
wouldrequirerevascularization.  Such      ate flows are not clearly separatedinto  rotic lesions. PET may also be used to
studies   would be expected be par
                           to             liveor deadtissue   simplyon thebasis studyendorganpharmacokinetics            di
ticularly helpful in patients most        of flow or 201T1 ptake.
                                                           u                       rectly rather than relying on blood
likelyto haveeitherdiaphragmatic  or         A study by Brunken et al. found levelsof cardiac drugs. These new
breast issue
        t    attenuationartifacts
                                with that 58% offixed thallium defects (ir            areas should represent some of the
201Tl r 99mTcadionuclides.
      o        r                     reversibly injured) were viable by               largest growth areas for PET's clinical
                                          FDG (32). Tamaki     obtained     similar   applications.
                                       resultswith 40% ofpersistent thallium                           Richard A. Goldstein
ASSESSMENT OF MYOCARDIAL defects                displayingFDG activity(33).                             James T. Willerson
VIABILITY USING RADIONUCLIDE Recent studies have suggested that                       University     of Texas Health Science
TRACERS                                reinjection of thallium at 4 hr in                                              Center
                                                                                                              Houston, Texas
                                                the
                                       creases number of segmentsclas
   One of the areas that PET is begin  sifiedas viable(34). Thallium redis
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    TheClinical
              Roleof Positron
                            Emission omography€¢
                                   T         â GoldsteinandWilerson                                                                                                   609

				
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