@ diagnosing pheochromocytoma. Although, on average, semi adrenomedullary imaging agent ‘I]Iodobenzylguanidine (‘1 MIBG) in man: quantitative indicies are highly discriminant, the overlap be evaluation by scintigraphy. J Nuc/ Med I983;24:672—682. 11. Khafagi FA, Shapiro B, Fig LM, Mallette 5, Sisson iS. Labetalol reduces iodine-l31 tween values observed in normal and abnormal adrenal medul MIBGuptakeby pheochromocytomaandnormaltissues.J NuciMed 1989;30:481— lae make them of little additional use in clinical practice. 489. 12. Metz CE. Basic principles of ROC curves analysis. Semin Nuci Med 1978;8:283—298. CONCLUSION 13. Hanley JA, McNeil BJ. A method comparing the areas under receiver operating We found that the adrenal medulla is more often visualized characteristics curves derived from the same cases. Radiology 1983;148:839—843. 14. Brown Mi, Fuller RW, Lavender JP. False diagnosis of bilateral phaeochromocytoma after injection of 74 MBq 13‘I-MIBGand that adequate inter by iodine-l31-labeled meta-iodobenzylguanidine (MIBG). Lancet 1984;i(8367):56— pretation ofa MIBG scan should take into account that 56% and 57. I5. Morais i, Le Marec H, Peltier P. et al. MIBG scintigraphy of a patient with 73% of normal glands are seen at 24 and 48 hr postinjection, pheochromocytoma on labetalol therapy. C/in Nuc/ Med 1992; 17:308—3I 1. respectively. Since 1989, the optimal visual score for diagnos 16. Wieland DM, Brown LE, Tobes MC. Imaging the primate adrenal medulla with [1231] ing pheochromocytoma is 3 or more. Thus, only an intense and [13t1] metaiodobenzylguanidine: concise communication. J Nuci Med 1981;22: 358—364. uptake should be considered to be positive. We could not find 17. Wafelman AR, Hoefnagel CA, Macs RAA, Beinen iH. Radioiodinated meta-iodoben any factor related to the patient recruitment and the scanning zylguanidine: a review of its distribution and phannacc@cinetics,drug interactions, protocol to explain this change. Therefore, we strongly suspect cytotoxicity and dosimetry. Eur J Nuci Med I994;2 I :545—559. 18. Solanki KK, Bomanji J, Moyes I, Mather Si, Trainer PJ, Britton KE. A pharmaco that the increase in SA of labeled MIBG during recent years is logical guide to medicines which interfere with the biodistribution of radiolabeled the probable explanation of the higher proportion of normal meta-iodobenzylguanidine (MIBG). Nuc/ Med Commun 1992; 13:513—521. adrenal medullae displaying visible uptake. 19. Tobes MC, Fig LM, Carey I, Geatti 0, Sisson JC, Shapiro B. Alterations of iodine-131 MIBGbiodistributioninananephricpatient:comparisontonormalandimpairedrenal REFERENCES function. .JNuc/ Med 1989;30:l476—1482. I- werbel SS. Ober KP. Pheochromocytoma: update on diagnosis, localization and 20. Huguet F, Fagret D, Caillet M, Piriou A, Besnard JC, Guilloteau D. Interaction of management. Med Cli,, North Am 1995;79:131—153. metaiodobenzylguanidine with cardioactive drugs: an in vitro study. Eur J Nuci Med 2. McEwanAJ.ShapiroB,SissonJC,BeierwaltesWH,AckeryDM.Radio-iodobenzyl 1996;23:546—549. guanidine for the scintigraphic location and therapy of adrenergic tumors. Semin Nuc! 2 1. Smets LA, ianssen M, Rutgers, M Ritzen K, Buitenhuis C. Pharmacokinetics and Med 1985:15:132—153. intracellular distribution ofthe tumor-targeted radiopharmaceutical m-iodo-benzylgua 3. Sisson JC, Frager M. Valk T, et al. Scintigraphic localization of pheochromocytoma. nidine in SK-N-SH neuroblastoma and PC-l2 pheochromocytoma cells. mt J Cancer NEngliMed 1981:305:12—17. 199 1;48:609—615. 4. Ackery DM, Tippett PA, Condon BR, Sutton HE, wyeth p•New approach to the 22. Mairs Ri, Cunningham SH, Russell I, et al. No-carrier-added iodine-13l-MIBG: localisation of phaechromocytoma: imaging with iodine-13 l-meta-iodobenzylguani evaluation of a therapeutic preparation. J Nuci Med 1995:36:1088—1095. dine.Br Medi 1984:288:1587—1591. 23. Lynn MD, Shapiro B, Sisson JC, et al. Portrayal of pheochromocytoma and normal 5. Shapiro B, Copp J, Sisson J, Eyre P. wallis J, Beierwaltes W. Iodine-13l metaiodo human adrenal medulla by m-['231]iodobenzylguanidine: concise communication. benzylguanidine for the locating of suspected pheochromocytoma: experience in 400 J Nuc/ Med 1984;25:436—440. cases. J Nuci Med 1985:26:576—585. 24. wafelman AR, Konings MCP, Hoefnagel CA, Macs RAA, Beijnen JH. Synthesis, 6. SwensenSi, BrownML, Sheps5G.et a!.Useof ‘@‘IMIBGscintigraphyin the radiolabelling and stability of radioiodinated m-iodobenzylguanidine: a review. App/ evaluation of suspected pheochromocytoma. Mayo C/in Proc 1985;60:299—304. Radial Isot 1994;45:997—1007. 7. Velchik MG, Alavi A, Kressel HY, Engelman K. Localization of pheochromocytoma: 25. wieland DM, wu i-I, Brown LE, Mangner Ti, Swanson DP, Beierwaltes @H. MIBG,CT, and MRIcorrelation.J Nuci Med 1989;30:328—336. Radiolabeled adrenergic neuron-blocking agents: adrenomedullary imaging with 8. Gross MD, Shapiro B. Scintigraphic studies in adrenal hypertension. Semin Nuc/ Med [‘311]iodobenzylguanidine.J Nuc/ Med 1980;21:349—353. @ 1989;19:l22—143. 26.VaidyanathanG,ZalutskiMR.No-carrier-addedsynthesisof ‘I]-iodobenzyl 9. Bomanji J, Levison DA, Flatman WD, ci al. Uptake of 231 MIBG by pheochromo guanidine. App/ Radial Isol 1993:44:621—628. cytomas. paragangliomas and neuroblastomas: a histopathological comparison. J Nuc/ 27. Mairs Ri, Gaze MN, watson DG, et al. Carrier-free ‘31l-meta-iodobenzylguanidine: Med I987;28:973—978. comparison of production from meta-diazobenzylguanidine and from meta-trimethyl 10. Nakajo M, Shapiro B, Copp J, et al. The normal and abnormal distribution of the silylbenzylguanidine. Nuci Med Commun 1994; 15:268—274. Changes in Radioiodine Turnover in Patients with Autonomous Thyroid Adenoma Treated with Percutaneous Ethanol Injection Alessandra Paracchi, Eugenio Reschini, Carlo Ferrari, Gianluigi Ciocia and Massimo Castellani Departments of Endocrinology and Nuclear Medicine, Ospedale Fatebenefratelli; Department ofNuclear Medicine, Ospedale Maggiore; and Department ofEndocrinology, Ospedale S Pio X, Milan, Italy

on scintigraphy.In the remaining9 patientswith only partial nodule In 24 patients with autonomous thyroid adenoma, we studied the destruction on scintigraphy, protein-bound 1311remained elevated hormonal pattern (free thyroxine, free triiodothyronine and thyroid although markedly reduced. Biologic half-life was shortened in 18 of stimulating hormone) and markers of radioiodine turnover before 24 patients beforetreatment; after treatment, it was normal in 18 of and after nodule ablation with percutaneous ethanol injection. 24 patients (13 of 15 with complete nodule ablation and 5 of 9 with Methods:The hormonalpatternwasstudiedbeforetreatmentand partial ablation).Conclusion: Ethanoltreatmentnormalizedthe at various intervals after nodule ablation. Changes in radioiodine turnover were studied measuring 1311protein-bound iodine and the hormonal pattern in all patients. Measuresof radioiodine turnover biologic half-lifeof radioiodinein the thyroid (calculatedfrom thyroid were better markers of residual disease in that they normalized in uptakeat24and48hr)beforeandafterethanoltreatment.Results: almost all patients with complete nodule ablation, whereas they The hormonal pattern was normalized by treatment in all patients remained abnormal in a high proportion of patients with incomplete and remained normal for the follow-up period. Before treatment, ablation. Thyroid hormones remained normal over a follow-up protein-bound 1311was elevated in all patients but 4; after treatment, period of 3-7 yr in all patients. it normalizedin 15 patientswith the disappearanceof the adenoma KeyWords:autonomousthyroidadenomapercutaneousethanol injection; ethanol injection Received Apr. 23, 1997; accepted Sep. 4, 1997. Forcorrespondence or reprints contact: Eugerno Reachini, MD, Department of Nuclear JNuclMedI998;39'.1012—I016 Medk@ne,Pad.Granelli,OspedaleMaggkre,@ñaF.Sforza35,20122MIaOO,ttaly.

1012 THEJOURNALOFNUCLEARMEDICINE‘Vol. 39 . No. 6 •June1998 Percutaneousethanolinjectionforthetreatmentoftheautonhormone levels and parameters of radioiodine turnover at baseline omous thyroid adenoma was proposed by our group in 1990 are reported in Table 1, Figure 1 and Table 2. All patients had (1 ). Subsequent reports by us and others (2—10)have confirmed suppressedserumTSH concentrations(<0.1 mU/liter). According the efficacy ofthis treatment, which is now an accepted method to the hormonal data, 15 were toxic (hormone levels above the ofnodule ablation (11). The results oftreatment werejudged on normalrange)and9 werenontoxic(hormonelevelsstill normal). the basis of changes in the hormonal pattern, particularly Thyroid uptakemeasurementswere performed 6, 24 and48 hr after changes in thyroid stimulating hormone (TSH) levels, and on oral administration of 1.85MBq ‘@‘Iusing a probe connectedwith qualitative changes in the scintigraphic appearance of the a scaler having a window centeredon the 364-keV photopeak of thyroid gland. In this article, we report changes induced by the radionuclide. Scintigraphy was performed at 24 hr with a ethanol treatment on radioiodine turnover in a group of patients rectilinear scanner.The biologic half-life of iodine in the thyroid with autonomous thyroid adenoma. was calculated from the uptake measurementsat 24 and 48 Kr; mean normal value is 65 days (14) and it was shortened when MATERIALS AND METhODS lower than 20 days (15). Protein-bound ‘@‘Iwas measured at 48 hr Since 1989, we have treated with percutaneous ethanol injection counting 4 ml of plasma after removal of the free iodine by an more than 200 patients with autonomous thyroid adenoma. The ion-exchange resin. Results were given as a percent of adminis main clinical and hormonal results have been published (1,2, 7). tered activity per liter of plasma (normal values < 0.3% dose per This article includes a subsetof24 patients in whom, in addition to the usual scintigraphic study with pertechnetate,we performed a liter of plasma). Free thyroid hormones in serum (normal range study with radioiodine (‘@‘I),including an uptake curve up to 48 hr, 7.7—19.3pmol/liter for FT4 and 4.0—8.6pmol/liter for FT3) were the determination of ‘@‘Iprotein-bound iodine at 48 hr, and assayed by radioimmunoassay according to Romelli et al. (16). scintigraphyat24hr. Thepatientsstudiedweretreatedin theearly Serum TSH was assayed by a sensitive immunoradiometric assay; years of ethanol use for nodule ablation, when a study with the results are given in units of the 80/558 reference preparation of radioiodine was associated with pertechnetate to be certain that the the World Health Organization (normal range 0.4—4.5mU/liter). nodules were not of the trapping-only type (12) and to collect The thyrotropin releasinghormone (TRH) test, done in 17patients @ parametersof dosecalculation for treatment with ‘Iin the event before treatment and in 22 after treatment, was performed by the the patient eventually preferred it to ethanol ablation. More intravenous injection of 200 @gof the peptide. Blood for TSH recently, we ceased using ‘1! for diagnosis and used ‘231for measurement was taken before injection and 20 and 30 mm after. dosimetry calculations (13). Among the patients who had the basal Normal peak levels of TSH after TRH range between 3 and 20 13 11 study, 24 had a repeat study after the treatment of the nodule mU/liter. with percutaneousethanol injection to investigate the changesin Nodule volume was measured by ultrasonography using the radioiodine turnover induced by treatment. Demographic data, formula for ellipsoids. Ethanol was injected into the nodulesby the

TABLE I Demographic Data, Nodule Volume and Treatment Modalities in 24 Patientswith Autonomous Thyroid Adenoma Treated with Percutaneous Ethanol Injection

Nodule (ml)*Cycles of ethanol Patientno. Age(yr) Sex Beforetreatmentvolume(ma)Aftertreatment treatmentInjected (metFollow-up 157M11+31.3+0.516+286248F140.911178370F141.511272428F171.211370562F142.421

969668M282.514467723F93.111766854M333.014065959M231.3217+7641058F61.5114641 1 +

20631251M343.2142621354F51.418541432F101.5122531554M332.7136531659M17+211.1+10126+4651749F254.5136641854F141.6119631945F232.0130632065F273.0126622140M6610.01142602241F82.0214161F231 .3214 +

4592364F83.019542439F117.211336Mean +

±s.d.51.4 ±12.420.7 ±13.73.1 ±2.627.8 ±26.863.0 ±9.5

*Pat@flts1 and 16 had two nodules. tForPatients1 and16 theamountof ethanolinjectedineachnoduleis reportedPatients5 9 11and22hadtwotreatmentcyclesina singlenodule.

THYROID FUNCTION AFTER ETHANOL ABLATION •Paracchi et al. 1013 @ @& W•@me@

@ J@ —-“-——@.-— ._I_ _ _ _1_ @._ . _@_ .@ _ A 1@1_ ___ @_1. - -- —---.--— : . — jl3I@

@ A@ B 30@

@ 40@ 25t @ t@°h@H•

@ 10 @ =:=::@“ @ r:L5' @______

0• @ @esbns@ ifter fr_ @v (mMn22.2±100) (mssn11.0 ±1.9) (inesri12.2±8.4) (m@@4.7 *0.0)

CaO@ D16

10 . @12

t.2. @0e. -@@--@ @8. FiGURE 1. Serum hormone levels before and after ethanol treatment in the 24 o:@@ patients studied. lndivklual data and @ mean values ±s.d. are shown. FT4. (B)FT3.(C)TSH basal.(D)TSHpeaks after TRH for only the 16 patients who (me@@ @1) (tviesn1.0*0.4) (inssi@<0.1) (mean7.1 ±4.0) had a TRHtest both beforeand after ethanoltreatment.

percutaneous route under ultrasound guidance as previously de radioiodine studies. The follow-up period after treatment is 3—7yr. scribed (2, 7). The total amount ofethanol injected was divided into All patients gave informed consent to the treatment and scinti 2—12injections(mean 6) made at 4- to 7-day intervals.The graphic studies. post-treatment ‘II radioiodine study was performed after resump tion of TSH secretionandcompletionof noduleshrinkage,gener RESULTS allyat least6 moaftertheendof treatment.Thehormonevalues The results of ethanol treatment on nodule volume, FT4 and reported in Figure 1 are those recorded at the time of the FT3 serum levels, TSH levels before and after TRH stimulation

TABLE 2 Parameters of Radioiodine Turnover Before and After Treatment with Percutaneous Ethanol Injection in 24 Patients with Autonomous ThyroidAdenoma

treatmentPatient BeforetreatmentAfter

ThyroiduptakeBIOIO9IC Thyroid uptakeBIOlOgIC half-life 1311 %/ half-life 1311 %/ no.%hr115.025.0hr6hr24 hr 48 (d)PIOtsinbOulldliter plasma% plasma6hr24 hr48 (d)Protsin-boundliter 20.03.10.1810.214.413.49.60.09227.035.0 27.02.72.330.745.444.534.60.14316.528.5 [email protected] 47.0x02023.138.642.40.16527.043.0 [email protected] .120.130.827.76.50.28728.042.4.335.5 29.03.41 .219.627.030.5x0.13826.834.1 37.65.81 [email protected] 37.44.04.432.343.042.342.20.651021.527.7 27.90.6639.149.448.748.50.241 .624.438.940.60.321227.039.0156.266.9 66.051 .11 35.06.41.330.141.845.0x0.191326.536.4 34.211.10.519.329.128.640.00.141429.638.0 .2216.50.231541.144.6 36214.30.5523.231 .331 43.838.30.9714.428.027.896.70.181633.243.4 .222.222.5x121716.522.1 33.02.53.21 1 .217.919.0x0.581834.049.0 18.74.11 .541 1 7.025.925.019.60.481951 44.06.40.521 .32.020.629.627.49.01.52031.055.7 52.41 1 36.110.824.938.338.8oc0.352130.156.0.638.5 .63222.235.826.1220.542212.319.6 36.11 15.52.91.514.419.015.13.00.592329.942.3 .82.124.142.446.6x0.452447.853.4 39.91 1 .42.5mean 43.93.56.534.540.741 ±s.d.30.5 ±11.5 40.3±11.3 36.0±11.01.6 ±1.521.6 ±7.8 32.1±9.831.9 ±10.70.48 ±0.5

1014 THEJOURNALOFNUCLEARMEDICINE•Vol. 39 •No. 6 . June 1998 A B of little importance in uptake measurements before treatment when radioactivity was confined to nodular tissue, and in cases of complete ablation, when radioactivity was almost entirely in the reactivated normal tissue. In cases of partial ablation, uptake measure reflected a combination of radioiodine content in residue of the nodule and in partially reactivated normal tissue. For these patients, the best technical approach would be an _%_. uptake study with a gamma camera, which allows separation of C D the uptake values of the two parts of the thyroid gland (nodule and extranodular tissue). We have used this method in recent @ .9 . FIGURE 2. Thyroid scintigraphy be@@ cases(13). Values of protein bound I3II likewise reflected the @ I, , .‘ fore (left) and after (right) ethanol degree of nodule destruction—normalized in almost all patients @ injection in two patients with auto with completeinactivationandabnormal,althoughreduced,in @ M nomous thyroid adenoma. (A,B) Complete nodule ablation (Patient patients with partial inactivation. Parameters of radioiodine “I, 12). (C, 0) Partial nodule ablation (Pa turnover appeared to be more sensitive indices of residual tient21). disease than the hormonal values. Once a nodule was suffi ciently damaged to allow resumption of TSH secretion, the and parameters of radioiodine turnover (biologic half-life and levels of circulating thyroid hormones became normal and no protein-bound I3II) are reported in Table 1, Figure 1 and Table difference was demonstrable between complete and partial 2. Marked reduction in nodule volume occurred in all cases. ablation. TSH levels showed wide overlap in the two groups of FT4 and FT3 serum concentrations were normalized in all cases patients as well, although a significant mean difference in both when previously elevated. TSH levels, undetectable and unre basal and TRH-stimulated TSH levels was demonstrated be sponsive to TRH before treatment, became both normal and tween patients with complete and partial nodule ablation ( 7@. normally responsive after therapy. On the basis of scintigraphic Studiesofradioiodine turnoverafter noduleablationwith I I1 appearance after treatment, the patients were categorized as therapy would be of interest because after successful radioio completely cured (Patients 1—15),when the nodule was no dine treatment residual nodule function can be demonstrated in longer visible or was replaced by a cold area within the a large proportion of patients in post-treatment scintigraphic reactivated normal tissue, or partially cured (Patients 16—24), studies (1 7—22).A discussion of the relative benefits of the when the nodule or parts of it were still visible above the three therapeutic methods of nodule ablation (surgery, radioio partially reactivated normal tissue (Fig. 2). This is a scinti dine and ethanol) was beyond the scope ofthis article. We have graphic distinction, because the hormonal pattern was not reviewed this topic elsewhere (23). Ethanol treatment was different in the two categories of patients. Parameters of cheaper than surgery and more expensive than radioiodine. The radioiodine turnover were markedly changed by treatment. In main advantage of ethanol over radioiodine was the virtual all but 4 patients, protein-bound 131! before treatment was absence of post-treatment hypothyroidism ( 7,23 ), whereas the elevated and it was essentially normalized after treatment in all prevalence of postradioiodine hypothyroidism was 12% (15 1 of completelycuredpatientsexcept1 (Patient9) in whomit was 1293 published cases) (23 ). The main disadvantage of the markedly reduced. In partially cured patients, protien bound 1311 ethanol treatment was the difficulty of sufficiently inactivating remained above the normal range, although it was greatly big nodules (over 40 ml in volume). However, ifthe nodule was reduced in most patients. Biologic half-life before treatment damaged sufficiently to decrease hormone production to an was shortened in 18 of 24 patients and after treatment it was extent that allowed resumption of TSH secretion, the results normalized in 18 of 24. Of the 6 patients with short biologic remained stable for several years. In the patients we have half-life after treatment, 4 were partially cured and 2 were treated to date, no cases of resuppression of TSH have been completely cured on the basis of scintigraphy appearance. seen, even among patients with nodules still partially visible on post-treatment scintigraphies. This phenomenon was probably DISCUSSION similar to what happens with radioiodine treatment, which Results of ablation by ethanol of the hyperfunctioning nod leaves a consistent proportion of nodules still visible (17—22). ules have been evaluated on the basis of changes in hormonal The absenceofpost-treatment hypothyroidism with ethanol was pattern, qualitative inspection of changes in scintigraphy and due to the complete sparing of extranodular tissue that in demonstration of reduction in nodule volume after treatment contrast can be partially damaged during radioiodine treatment (1—10). In the small series presented here, we included param (13,24). eters of radioiodine turnover. Although our study had several technical limitations due to the fact that the data were derived CONCLUSION from diagnostic studies, the results are of interest. One draw Parameters of radioiodine turnover are sensitive markers of back was the fact that the biologic half-life was obtained from inactivation of hyperfunctioning thyroid nodules by percutane only two points of uptake measurement(24 and 48 hr). Since ous ethanol injection. They reflect the presence of residual hyperfunctioning nodules generally have rapid iodine turnover, disease more accuratelythanthe measurementof TSH and free the phenomenon of dismission was easily demonstrated under thyroid hormones in serum. these conditions of uptake measurement. The results of our study clearly showed the shortenedhalf-life before treatment REFERENCES and the correction after treatment in the majority of patients I . Livraghi T, Paracchi A, Ferrari C, et al. Treatment ofautonomous thyroid nodules with especially those with complete nodule ablation. In patients with percutaneous ethanol injection: preliminary results. Radiology l990;I 75:827—829. 2. Paracchi A, Ferrari C, Livraghi T. et al. Percutaneous intranodular ethanol injection: a partial ablation, radioiodine half-life remained frequently short new treatment for autonomous thyroid adenoma. J Endocrinol Invest 1992;15:353— due to the presence of different degrees of residual autonomous 362. 3. Monzani F, Goletti 0. Caraccio N, et al. Percutaneous ethanol injection treatment of tissue. Anothertechnical limitationwas the fact thatuptakewas autonomous thyroid adenoma: hormonal and clinical evaluation. C/in Endocrino/ measured with a probe seeing the entire thyroid gland. This was (Oxford)1992:36:491—497.

THYROID FUNCTION AFTER ETHANOL ABLATION •Paracchi et al. 1015 4. Martino E, Murtas ML, Loviselli A, et al. Percutaneous intranodular ethanol injection eds. MIRD primer for absorbed dose ca/cu/ations. New York: Society of Nuclear for treatment of autonomously functioning thyroid nodules. Surgen' 1992;! 12:1161— Medicine; 1988:49—54. 1165. 15. 5olomon DH. Factors affecting the fractional rate of release of radioiodine from the 5. Papini E, Panunzi C, Pacella CM, et al. Percutaneous ultrasound-guided ethanol thyroid gland in man. Metabo/ism 1956;5:667—681. injection: a new treatment of toxic autonomously functioning thyroid nodules? J C/in 16. Romelli PB, Pennisi F, VancheriL. Measurementof free thyroidhormonesin serum Endocrino!Mezab 1993;76:4I1—416. by adsorption chromatography and radioimmunoassay. J Endocrinol Invest 1979:2: 6. Mazzeo 5, Toni MG, Dc Gaudio C, Ct al. Percutaneous injection of ethanol to treat 25—40. autonomous thyroid nodules. Ant J Roenigenol 1993;I61 :871—876. 17. Molnar GD, Wilber RD. Lee RE, Woolner LB. Keating FR. On the hyperfunctioning 7. Livraghi T, Paracchi A, Ferrari C, Reschini E, Macchi RM, Bonifacino A. Treatment solitary thyroid nodule. Mayo C/in Proc l965;40:665—684. ofautonomous thyroid nodules by percutaneous ethanol injection: a 4-year experience. 18. Horst W, RosIer H, Schneider C, Labhart A. Three-hundred six cases of toxic Radiology1994:190:529—533. adenoma: clinical aspects, findings in radioiodine diagnostics, radiochromatography @ 8. Ozdemir H, Ilgit ET. Yucel C. et al. Treatment of autonomous thyroid nodules: safety and histology; results of ‘‘Iand surgical treatment. J Nuc/ Med 1967:8:515—528. and efficacy of sonographically guided percutaneous injection of ethanol. Am J 19. Blum M, Shenkman L, Hollander Cs. The autonomous nodule of the thyroid: Roenigenol I994:163:929—932. correlation ofpatient age, nodule size and functional status. Am J Med Sci 1975:269: 9. BraunB. BlankW. Farbdopplersonographischgestenerteperkutanealkoholinstillation 43—50. zur therapie der funktionellen schilddrusenautonomie. Dtsch Med Wochenschr 1994; I19:1607—1612. 20. Ng Tang Fui SC, Maisey MN. Standard dose ‘@‘ltherapy for hyperthyroidism caused by autonomously functioning thyroid nodules. C/in Endocrino/ (Oxford) l979;I0:69— 10. Di Lclio A, Rivolta MR. Casati M, Capra M. Treatment of autonomous thyroid nodules: value ofpercutaneous ethanol injection. Am fRoenigenol 1995:164:207—213. 77. I I. Hay ID. Moms JC. Toxic adenoma and toxic multinodular goiter. In: Braverman LE, 21. Kinser JA. Roesler H, Furrer T, Grutter D, Zimmermann H. Nonimmunogenic Utiger RD. eds. Werner and Ingbar @cthe ths'roid: Afundanienta/ and c/inica/ text, 7th hyperthyroidism: cumulative hypothyroidism incidence after radioiodine and surgical ed. Philadelphia-New York: Lippincott-Raven; 1996:566—572. treatment. J Nuc/ Med 1989;30:I960—l965. 12. Reschini E, Catania A, Ferrari C. Bergonzi M, Paracchi A. Raineri P. Comparison of 22. Nygaard B, Jarlov AE, Hegedus L, Schaadt B, Kristensen LO. Hansen JM. Long-term @ pertechnetate and radioiodine thyroid scintiscans in thyroid disease. J Nuc/ Bio/ Med follow-up of thyroid scintigraphies after ‘‘1therapy of solitary autonomous thyroid l993;37:I2—I7. nodules. Thyroid 1994;4:167—I71. 13. Reschini E, Matheoud R, Canzi C, et al. Absorbed dose estimate in nodular and 23. Ferrari C, Reschini E, Paracchi A. Treatment of the autonomous thyroid nodule: a extranodular tissue by quantitative iodine-l23 imaging before iodine-l3 1 radiotherapy review. Eur J Endocrino/ 1996:135:383—390. for autonomous thyroid adenoma [Abstract]. J Nuc/ Med 1996;37(suppl):230P. 24. Clerc J, Dagousset F. Izembart M, et al. Radioiodine therapy of the autonomous 14. Berman M, Braverman LE. Burke J, et al. Report No. 5. 1-123. 1-124, 1-125, 1-126, thyroid nodule in patients with or without visible extranodular activity. J Nuc/ Med 1-130, 1-131. and 1-132 as sodium iodide. In: Loevinger R, Budinger TF, Watson EE, l995;36:2 17—223.

Fluorine-18-FDG PET Imaging Is Negative in Bronchioloalveolar Lung Carcinoma

Kotaro Higashi, Yoshimichi Ueda,HiroyasuSeki, Kokichi Yuasa,ManabuOguchi, TetsuhikoNoguchi, Mitsuru Taniguchi, Hisao Tonami, Tetsuro Okimura and Itaru Yamamoto Departments ofRadiology, Internal Medicine, Pathology and Thoracic Surgery, Kanazawa Medical University, Kahoku-gun, Ishikawa; and Department ofRadiology, Kanazawa Cardiovascular Hospital, Kahoku-gun, Ishikawa, Japan

differentiated adenocarcinomas (4.63 ±1.86) (p = 0.031). No The goals of our study were to eStabliShPET accuracy wfth 18F- significant differenceswere apparent in average size among these fluorodeoxyglucose(FDG)in finding lOcalizedformationsof bronchi three histologk@types. Conclusion: A correlatlon was observed oloalveolarlung carcinoma (BAG)and to investigatethe correlation between FDG uptake and the degree of cell dffferentuatkn in between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung. FDG PET may show negative results adenocarcinomaof the lung. Materials: Twenty-nine patients wfth for BAG. 30 adenocarcinomasof the lung (7 bronchioloalveolarlung carcino mas, 9 well differentiated,2 well-moderatelydifferentiated,11 mod Key Words: PET;fiuorine-18-fluorodeoxyglucose; bronchioloalveo erately differentiated and 1 poorly d@1ferentiated)were studied. ,@Jl lar lung carcinoma patients underwent thoracotomies within 4 wk after the FDG PET J NuciMed1998 39.1O16-1OZ@ study. For qual@abveana@,sis,the degree of FDG actMty in the tumors was visuallyscored using a five-point grading system: 0 = same to background activity, 1 = less than mediastinalblood-pool PETwith18F-fluorodeoxyglucose(FDG)mayplayavaluable activity, 2 = same to mediastinal blood-pool activity, 3 = slightly role in delineating viable tumor tissue due to FDG PET's ability greater than mediastinal blood-pool activity and 4 = substantially to detect a tumor's increased glucose metabolism. It is known greater than mediastinal blood-pool actlvfty. Foci of activity with that malignanttumorstend to show higher metabolicdemands Grades2-4 were consideredtumors. For semk@uantitativeanalysis, than normal tissues. Recent articles have indicated FDG PET's standardized uptake values (SUV)were calculated. Results In 7 value in diagnosing human lung cancer (1—7).FDG PET has a BAGs,4 lesions(57%)showednegativeresultson FOGPET,while sensitivity and specificity of 93% and 88%, respectively, for in 23 non-BAGs,only 1 lesion(4%),which was a well-differentiated adenocarcinoma showed a negative result. BAGs' mean visual detecting malignancy in indeterminate solitary pulmonary nod score (1.43 ±1.27)was significantly lower than that of non-BAGs ules (7). However, wide variations in glucose consumption exist (3.17 ±1.03)(p = 0.001).The BAGs' meanSUV(1.36 ±0.821)was among individuals depending on the type of neoplasm. In cases significantlylower than that of well-differentiatedadenocarcinomas of malignant lung neoplasms,few negative results of malig (2.92 ±1.28) (p = 0.014); the mean SUV of well-differentiated nancy have been reported using FDG PET (4,5,8). Negative adenocarcinomas was significantly lower than that of moderately results have occurred in patients with bronchioloalveolar lung carcinomas (BACs) (4,8). BAC is a form of peripheral lung Received May 2, 1997; accepted Sep. 4, 1997. adenocarcinomagrowing as a single layer of malignant cells For correspondence or reprints contact: Kotaro Higashi, MD, Department of Radiol ogy, Kanazawa Medkal University, 1-1, Daigaku, Uchinada, Kahoku-gun, Ishikawa, along the walls of terminal airways (9). It is known that the 920-02, Japan. tumor growth rate for BACs is lower than that for non-BAC

1016 THEJOURNALOFNUCLEARMEDICINE•Vol. 39 •No. 6 •June 1998