7. Shapiro B, Gross MD. Radiochemistry, biochemistry, and kinetics of ‘31I-metaiodo 17. Bonnin F, Lumbroso J, Tenebaum F, Hartmann 0, Parmentier C. Refining interpre benzylguanidine (MIBG) and ‘23I-MIBG:clinical implications of the use of I23I@ tation ofMIBG scans in children. JNuc/ Med I994;35:803—8l0. MIBG. MedPedOncol 1987;15:170—177. 18. Osmanagaoglu K, Lippens M, Benoit Y, Obrie E, Schclstraete K, Simons M. A 8. Wafelman AR, Hoefnagel CA, Macs RAA, Beijnen JH. Rathoiodinated metaiodoben comparison of iodine-l23-metaiodobenzylguanidine scintigraphy and single bone zylguanidine: a review of its biodistribution and pharmacokinetics, drug interactions, marrow aspiration biopsy in the diagnosis and follow-up of 26 children with cytotoxicity and dosimetry. Eur J NucI Med 1994;21:545—559. neuroblastoma. Eur J Nuc/ Med 1993;20:1 154—I160. 9. Paltiel Hi, Gelfand Mi, Elgazzar AH, Ctal. Neural crest tumors: ‘231-MIBGimaging 19. Lebtahi Hadi-Djilani N, Lebtahi N-E, Bischof Delaloye A, Laurini R, Beck D. in children. Radiology 1994;190:1 17—121. Diagnosis and follow-up of neuroblastoma by means of iodine-123 metaiodobcnzyl 10. Evans AE. Staging and treatment of neuroblastoma. Cancer l980;45:1799—1802. guanidine scintigraphy and bone scan, and the influence ofhistology. EurJNuc/ Med 11. Mangner Ti, Wu J-I, Wieland DM. Solid-phase exchange radioiodination of aryl 1995;22:322—329. iodides. Facilitation by ammonium sulfate. J Org Chem 1982;47:1484—88. 20. Rufini V, Giordano A, Di Giuda D, et a!. Iodine-123-MIBG scintigraphy in 12. Lynn MD, Shapiro B, Sisson JC, et al. Pheochromocytoma and the nonnal adrenal neuroblastoma: a comparison between planar and SPECT imaging. Q J Nuc/ Med medulla: improved visualization with ‘231-MIBGscintigraphy. Radiology 1985;156: 1995;39(suppl 4):25—28. 789—792. 21. Englaro EE, Gelfand Mi, Harris RE, Smith HS. Iodine-131-MIBG imaging after bone 13. Shulkin B, Shapiro B, Francis I, Door R, Shen 5-W, Sisson JC. Primary extra-adrenal marrow transplantation for neuroblastoma. Radiology 1992;182:515—520. pheochromocytoma: a case of positive ‘231-MIBGscintigraphy with negative @‘I 22. Lastoria S, Maurea 5, CaracéC, et al. Iodine-131-metaiodobenzylguanidine scintig MIBG scintigraphy. C/in Nuc/ Med 1986;! 1:851—854. raphy for localization of lesions in children with neuroblastoma: comparison with 14. Sinon B, Hoefnagel CA, deKraker I, van5teeg 0, ValdésOlmos RA. Iodine-123- computed tomography and ultrasonography. Eur J Nuc/ Med 1993;20:l 161—1167. MIBG or ‘311-MIBGfor imaging ofneuroblastoma? A comparative study [Abstract]. 23. Hoefnagel CA, Marcuse HR. deKraker J, Voute PA. Methodology and problems of EurfNuc/Med 1992;19:589. single photon emission tomography using 1311-metaiodobenzylguanidine. Der 15. Gordon I, Peters AM, Gutman A, Morony 5, Dicks-Mireaux C, Pritchard J. Skeletal Nukieramedizine1987;4:317—323. assessment in neuroblastoma: the pitfalls of iodine-123-MIBG scans. J Nuc/ Med 24. Gelfand Mi, Elgazzar AH, Kriss VM, Masters PR, Golsch GJ. Iodine-123-MIBG l990;3 1:129—134. SPECT versus planar imaging in children with neural crest tumors. J Nuc/ Med 16. Corbett R, Fullbrok A, Meller 5, Flower M. Iodine-123-metaiodobenzylguanidine 1994;35:1753—l757. single photon emission computed tomography in the assessment of children with 25. Dessner DA, Di Pietro MA, Shulkin BL. MIBG detection of hepatic neuroblastoma: neuroblastoma. Prog C/in Bio/ Res 1991;366:479—485. correlation with CT, US and surgical findings. Ped Radio/ l993;23:276—280. Fluorine- 18-FDG and Iodine- 13 1-Iodide Uptake in Thyroid Cancer

Ulrich Feine, Roland Lietzenmayer, Jacek-P. Hanke, JUrgen Held, Helmut Wöhrleand Wolfgang MUller-Schauenburg Department ofNuclear Medicine, Eberhard Karls University, Tuebingen, Germany

raphy, ultrasound, CT and MR offer additional control We conducteda prospectivestudyto definethe sensitivityof 1311 methods during follow-up. Newer scintigraphic examinations with scintigraphy and l8@J(@p@ whole-body scanning in the detection 201T1-chloride, @Tc-sestamibiand ‘1‘In-octreotide,the latter for of thyroid cancer and metastases. Methods Forty-one patients with dtfferentiated thyroid carcinoma who underwent thyroidectomy diagnosing C-cell carcinoma, have not been completely evaluated and 1311elimination ofthe remaining thyroid were studied by 18FDG clinically (2). whole-body PET in 52 examinations and by 1311whole-body scan After ‘@‘ielimination of remaining thyroid tissue, increasing ning. Results Combined 18FDG and 1311imaging resulted in a hTg levels need to be evaluated. In conventional diagnostic senstivity of about 95%, with alternating uptake of 1311and 18FDGin procedures, hTg-producing tissue cannot always be localized. the metastases: 1311trapping metastases with no 18FDGuptake and With 2-['8F]-fluorodeoxyglucose (‘8FDG),it is possible to 18FDGtrapping metastases with no 1311uptake. Five uptake types detect malignant tumors with a sensitivity of 80%—90%(3). were differentiated. Alternating uptake was found in about 90% of However, a few published studies report absence of ‘8FDG the patients, which was nearly identical to the sensitMty of the uptake in thyroid carcinoma (4—6). combined 131It8FDG investigation. In six patients with increasing This prospective study was designed to define the sensitivity human thyroglobulin levels, we found that 18FDGwhole-body PET localized positive neck metastases of papillary thyroid carcinomas of thyroid cancer and metastases detection with ‘8FDGwhole that were histologically confirmed after extirpation. Conclusion: body PET in combination with ‘@‘Iwhole-body scanning. Combination 18FDGand 1311whole-body imaging protocol enables detection of local recurrence or metastases on whole-body scans that are often not shown by other imagingmethods. Biochemical MATERIALS AND METhODS grading of thyroidcancer may also be possible withthis method: Forty-one patients with differentiated thyroid carcinoma after Tumors with remainingfunctional differentiationfor hormone syn thyroidectomy and 1311 elimination of the remaining thyroid tt@s and iodine uptake have low glucose metabolism in more than underwent follow-up ‘8FDGwhole-body PET studies from Dc 95%; tumors without this functional differentiationof 1311uptake cember 1993 to August 1995. Twelve patients had papillary show high glucose metabolism. fluorine-I 8-FDG uptake seems to carcinoma, 23 had follicular carcinoma and 6 had Hürthle-cell be an indicatorof poor functionaldifferentiation,and possiblyhigher carcinoma. Three additional patients with C-cell carcinoma, all malignancy, in thyroid cancer. MEN II, and with elevated calcitonin levels had no uptake of KeyWords:fluorine-lB-FOGPET;thyroidcarcinoma;iodine-i31 ‘8FDGand were not reported in this study. All patients underwent J NucI Med 1996;37:1468-1472 1311 whole-body gamma camera imaging, neck and abdominal US, CT and hTg level determination. All patients gave informed consent for participation in the study. Human thyroglobulin(hTg)determinationfor the detectionof The ‘8FDGwhole-body PET results were systematically com local tumor recurrence and metastases and 1311whole-body scan pared with the results from the methods mentioned above, espe ning are well-established methods in the follow-up ofpatients with cially with ‘@‘Iwhole-body scans. All examinations were per thyroid carcinoma (1). Other imaging procedures such as radiog formed not more than 4 wk before or after the PET study. The l8}@W@Qstudies were performedon a scannerwith whole-body Received Aug. 7, 1995; revIsion accepted Mar. 14, 1996. For correspondence or reprints contact Ulnch Felne, MD, Department of Nuclear and high-sensitivitymodes. The field ofview (FOV) was 15 cm; 5-7 Medicine, University of Tuebngen, Roentgenweg 13, D-72076 Tuebngen, Germany. FOV = 75-105-cm body scan. The patientsfasted 18 hr priorto the

1468 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 9 . September 1996 TABLE 1 substitution. Four patients examined with ISFDG without thyroxin 18FDG/131IUptake Type and Histology of Thyroid Cancer substitution received thyroxin substitution at a later time.

patientsType18FDG-positive/131l-negative18FDG-negative/131!-positiveMixedof Uptake RESULTS typeIIIIIIIVVNumber Total4cell Thirty-four of 41 patients had increased hTg levels (>1 ng/ml), indicative of local recurrence or métastases.In nine 196— patients, other imaging methods (CT, MR, ultrasound, 131I whole-body scintigraphy, 2()1T1scintigraphy, 99mTc-MDP skel etal scintigraphy) and, in three patients, 99mTc-MIBI scintigra phy provided no satisfying explanation for the elevated hTg type*18FDG- 542i levels. Seven patients were hTg-negative (<1 ng/ml) but had and131l-positive18FDG- suspicious findings after palpation or neck ultrasound or in follow-up after therapy. and131l-negativePapillary7T1112*Follicular85433«Hürthle7 We found alternating behavior between 131I and I8FDG uptake in the métastasesof 30 patients: métastasesthat trapped I showed no uptake of I8FDG and non-'311 trapping métas Total 12 23 41 tases exhibiting high ISFDG uptake. Moreover, the métastases with high 18FDG uptake were easily differentiated from normal Type III: either l8FDG-positive/131l-negative or l8FDG-negative/131l-pos- tissue and those métastasestrapping I31I. FDG whole-body PET itive (mixed type). detected non-1311 trapping métastasesof thyroid carcinomas in fFour patients with postoperative histologically confirmed carcinomas. papillary or follicular carcinoma as well as Hürthlecell thyroid Two of them were hTG-negative prior to surgery. carcinoma in about 95% of the patients. Four Hürthlecell *One true-negative (hTG < 1 ng/ml) and one false-negative (hTG < 10 carcinomas were also 18FDG-positive/l3'l-negative. ng/ml). Table 1 presents the five different types of FDG/'31I uptake §Twotrue-negative (hTG < 1 ng/ml) and one false-negative (hTG > 100 ng/ml) after radioiodine therapy. and classifies the uptake patterns histologically. Figures 1 ^True-negative (hTG < 1 ng/ml). through 4 depict patients with types I-IV uptake. Two of 19 patients with type I uptake had hTG levels <1 ng/liter, but palpation of the neck region revealed suspicious injection of I8FDG (5 MBq/kg body weight). Imaging began 45 nodules. Ultrasound could not differentiate these nodules from min postinjection. The scan time for one FOV was 5-7 min. benign alterations, but the I8FDG scans were positive for métas Transmission correction was performed for quantitative evalua tases, which were histologically confirmed as papillary carcinoma. tion of tumor uptake in 31 examinations. Standardized uptake In five of seven patients with I8FDG- and I-negative scans, values (SUVs) were calculated and corrected for body weight other imaging methods or clinical parameters did not confirm (SUVbw) and body surface area (SUVbsa), as described by Kim et métastases.Only two patients had I3II- and '''FDG-negative al. (7). A correction for the finite resolution with recovery scans after completing 13II therapy. coefficient was not necessary for the evaluated métastasesbecause The I3'I and '8FDG uptake patterns in 184 métastasesof 26 of métastasessize (>18 mm) and the high resolution of the scanner patients are shown in Table 2. Standardized uptake values (8). For I3II whole-body scanning, we used a scanner with two (SUVbw) in IXFDG trapping métastasesof uptake pattern type 1, opposite large-field gamma camera detectors and high-energy were >3.79 (range 3.79-5.21 ) and <2.48 (range 0.77-2.48) for collimators. The I31I dose was between 100 MBq and 6 GBq uptake pattern type II. These values confirm the good visual (therapy doses), and patients were scanned 48 hr to 5 days after discrimination of the 18FDG-positive métastasesfrom normal tracer administration. tissue. The SUVbsa yielded similar results and relations with the All thyroid carcinoma patients were examined for '•"!uptake corresponding count values. without hormone substitution at high TSH levels. FDG-PET was We did not observe any significant difference in metastatic performed before or after ml whole-body scanning; some ISFDG IXFDG uptake in patients with or without thyroid hormone whole-body scans were obtained after the patient began thyroxin substitution (i.e., with high or low TSH levels). Additionally,

t -

FIGURE 1. Uptake pattern type I in a 56-yr-old woman with papillary thyroid cancer, 8 yr after surgery and 1311ablation of the remaining thyroid. Two locore- gional recurrences were surgically re moved, and there is now slight increase of hTg to 4.2 ng/liter. FDG whole-body PET shows three 18FDG-positive nodules 18.05.94FDG-GK in the jugulum which were histologically Lotto Z..5SJ. Pipili. SD-Ca. Rezidiv? Nuklearmedizin confirmed as métastasesof a papillary „PETTUEBINGEN thyroid carcinoma.

ALTERNATINGFLUORINE-18-FDGANDIODINE-!31 IODIDEUPTAKEINTHYROIDCANCER•Feine et al. 1469 A 99m1cMDP 131.1W8

@ 1.: ‘ ;@j@ @*

*@,

tollicular Thyroid Ca. @ernann F..S1 years @ t

FIGURE 2. Uptake pattern type IIin a 48-yr-old man with folhcularcarcinoma The patient underwent the first 1311therapy 3 mo ago and is now undergoing @ a second 1311therapy. Technetium-99m-MDPbone scan (left)shows onlyone smallfocus inthe spne whichis [email protected] (nght)after second radioiodinetherapy session shows restingmultipleuptake foci.(B)FDGwhole-body,PET-negativescan. Noncorrectedscans above, corrected scans below.

four patients, controlled with and without thyroxin substitution metastases with a sensitivity of about 94%. In patients with and with low or respectively high TSH levels, did not exhibit ‘311-positivemetastases, only a few metastases also exhibited significantly different uptake patterns. ‘8FDGuptake. In five patients with ‘311-negativemetastases, To date, we have not performed FDG-PET studies before and CT, MM, US or 201Tlscintigraphy could not detect metastases. after thyroid ablation in patients who had recurring metastases All positive 18FDG-PET studies resulted in tumor extirpation after thyroid removal to compare with 1311scans to determine and histological confirmation of the metastases. Seven of 41 changes, if any, in ‘8FDGuptake. patients had negative ‘@II and ‘8FDGmetastases. Only two patients with metastases confirmed by chest radiography and DISCUSSION neck ultrasound had false-negative 1311and ‘8FDGresults. Both In patients with elevated or increasing hT@ who had no patients had undergone repeat 131Jtherapy. Therefore, the combi metastases with ‘@11 uptake, we could detect ‘8FDG-positive nation of ‘@‘Iand ‘8FDGwhole-body scanning has the highest sensitivity in the detection of thyroid carcinoma metastases. 1311 18FDG Earlier investigations have only reported irregular ‘8FDG uptake in thyroid tumors and metastases, but these findings were not correlated to 1311uptake (5,6,12,13). .@, The alternating uptake pattern of ‘31L/'8FDGwe observed in 30 patientswith thyroidcarcinomaandmetastasesenabledusto identify five uptake patterns (9). In 90% of the metastases, there was no continuous, reverse relationship in ‘8FDGor 1311uptake levels. There was, how ever, a “yes/no―or “no/yes―state in visual analyses that can be L confirmed quantitatively (SUVbW). Within these five uptake patterns, we could identify three uptake levels in 34 patients with metastases:

1. At the patient level, type I and II (25 patients). 2. At the metastasis level, type I—Ill(30 patients). 3. At the cellularlevel (hypothetical),type I—IV(34 patients).

TABLE 2 Comparison 18FDGt31I Uptake in 184 Metastases in 26 Thyroid @ ‘p. Cancer Patients

RVL I @. RVL thyroki thyroid UptakecarcinomaI62typePapillarycarcinomaFolhcular carcinomaHUrthIe-cell FiGURE3@Uptake pattern type Ill in a 63-yr-old woman with var@ng differentiatedpapillarythyroidcarcinoma Iodine-131scan shows high 1311 metastasesII18metastases59 metastases8 uptake inthe metastases but no uptake inlungand other metastases whk@h metastasesIV3metastases, (2 partially were depicted on radiOgraphS.FDGWhole-bOdyPET shows three times 18FDG-positive)30 more marked metastases, none whichtrapped 1311.(Left)1311whole-body metastases4 metastases scan and (right)18@ whole-bodyPETscan (sinogramprojection).

1470 THE JOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 9 •September 1996 A ‘8FDGuptake in the cold nodules (99mTc@pertechnetate/l3hI@ negative). Three of these histologically confirmed benign ade nomas were Hürthlecell adenomas without signs of malignancy but exhibiting high hTg levels (258; 530; 460 ng/ml). The adenomas in the other two patients were not examined histo logically. Bloom et al. (10) also described eight patients who . S had ‘8FDG-positivebenign thyroid adenomas with an FDG dose uptake ratio (DUR) <7.5. The PET data, on the basis of these DURs, could differentiate between benign (<7.5) and 11 malignant (>8) throid adenomas. We did not find any hot nodules that were 1 FDG-positive. Voth et al. (13) also reported elevated ‘8FDGthyroid uptake in Basedow disease. We did not observe significance correlation between ‘8FDG uptake and thyroid hormone levels (TSH stimulation or sup pression). A similar correlation between glucose uptake and cell FIGURE4. Uptake pattern type IV in a 58-yr-old woman who had a Urge differentiation has been demonstrated in other malignant tumors tumor in the right 5ip for more than 15 yr that progressed in the last months such as astrocytomas and glioblastomas (15). We also observed @ and was not treated before with I. Two metastases had FDG arid ••I this correlation in eight patients with neuroblastoma: The two uptake but indifferentareas ofthe metastases. @t)1311whole-bodyscan and better differentiated ganglioneuroblastomas were ‘8FDG-nega (B)18@[email protected] (SUV@:3.79)and AOl2 (SUV,,,,:1.86)showed differentuptake regions in tive and ‘231-MIBG-positive,as were the eight neuroblastomas. one metastasis. AOl 4 (SUV@,,,:4.07) showed a lung metastasis without 1311 We also observed five hepatocellular carcinomas, of which two uptake. ROIs4 (SUV@:1.54)and 7 (SUV@:4.30)seem to be inthe same fibrolamellar carcinomas did not exhibit ‘8FDGuptake, possi metastasis but in two other differentiated regions. bly because of their higher differentiation. Therefore, ‘8FDGuptake appears to permit grading of tumor Thirty-four patients showed ‘8FDGand/or 1311uptake: 30 of differentiation and malignancy in thyroid cancer as well as them exhibited the flip-flop phenomenon at the patient level, other carcinomas. Increased glucose metabolism could be a five had the mixed type III; and 4 both uptake of ‘8FDGand general indicator for higher graded tumors in oncology. 131! Five percent of the metastases had both 1311 and ‘8FDG uptake. In those patients with simultaneous uptake of ‘8FDG CONCLUSION and 1311the SUVbw were relatively low and might be caused by A dual study with ‘8FDGand ‘@‘Iprovides a sensitivity of a mixture of different tumor cells in these metastases. It is not 95% for the detection of recurrent thyroid cancer. This sensi yet clear whether the same cells can take up iodine and FDG or tivity rate enables detection of local recurrence or metastases whether there are two different cell types in one metastasis. We with whole-body imaging that are often not revealed by other observed alternating 1311and ‘8FDGuptake in different regions imaging methods. It also appears possible that a lack of ‘8FDG of the same metastasis in two larger metastases (Fig. 4). This uptake and residual 1311uptake in metastases represents higher phenomenon may be explained by the hypothesis that function functional tumor differentiation. Additional studies with larger ally more differentiated thyroid carcinoma cells with normal patient populations may show whether this diagnostic test also low glucose metabolism and remaining 1311uptake can later indicates better prognosis. It seems that we could obtain a change to a high glucose metabolic state that corresponds to the biochemical grading for the functional differentiation of thyroid newly dedifferentiation of the cells. carcinomas with the alternating uptake of 1311and ‘8FDG. We believe that uptake type II, ‘31I-positive/'8FDG-negative, seems to represent functionally better differentiated low-grade ACKNOWLEDGEMENTS tumor cells; whether the prognosis for the patient is better must still We thank the staff of the Department of Diagnostic Radiology be evaluated. Conversely, type I uptake, ‘8FDG-positive/'311neg (Prof. Dr. C.D. Claussen) for their assistance with the radiography, ative, represents higher malignancy of the tumor cells with lower CT and MR studies and the Section of Radiopharmacy (Prof. H.-J. functional differentiation. The mixed type III seems to represent Machulla) for their cooperation. We extend special thanks to Prof. metastases of type I and type II [i.e., different degrees of differ R. Lambrecht, PhD, Visiting Professor at the PET Center, Univer entiation occur in metastases in the same patient çseeFig. 3)]. sity of Tuebingen, for editorial assistance. The relative benignancy of tumors with high @‘Iuptake and no ‘8FDGuptake was demonstrated in three patients with REFERENCES follicular thyroid carcinoma, in whom the metastases had 1. Ng TF, SC, Hoffenberg R, Maisey MN, Black E. Serum thyroglobulin concentrations already been detected for 3 1, 15 and 6 @,‘r,respectively. and whole-body radiodine scan in follow-up of differentiated thyroid cancer after Multiple bone metastases exhibiting 311uptake and typical thyroid ablation. Br Med J I979;2:298—300. 2. Lawson M, Dusick D, Bandy D, Ctal. Comparison of “-FDGand 201Tl for detection radiographs were not visible on 99mTc..MDP bone scans or of recurrent metastatic differentiated thyroid cancer [Abstract]. J Nuc/ Med 1995; ‘8FDGscans. This indicates the relative benignancy of the 36(suppl):203P. 3. Strauss L, Conti PS. The applications of PET in clinical oncology. J Nuc/ Med tumor in the four patients with uptake pattern type II (Fig. 2). 199l;32:623—648. The absence of phosphonates trapping in bone metastases 4. BörnerAR, voth E, Schicha H. Fluorine-I8-FDG PET in patients with immunogenic seems to provide similar information about tumor malignancy hyperthyroidism prior to radioiodine therapy. Nuklearmedizin 1994;33:A81. 5. Joensuu H, Ahonen A. Imaging of metastases of thyroid carcinoma with fluorine-l8- as does the absence of ‘8FDGuptake. This low sensitivity fluorodeoxyglucose. J Nuc/ Med 1987;28:9l0—9I4. (—60%)in bonemetastasesfortrappingphosphates/phospho6. Matsuno N, Minoshima 5, Imazeki K, et al. Diagnostic values of ‘FDG-PET in nates was described by Castillo et al. (14) for differentiated primary and metastatic thyroid cancer. J Nuci Med l995;36(suppl): 196P. 7. Kim UK, Maresh C, Alavi A, Ctal. Standardized uptake values of ‘FDG:body surface thyroid carcinoma metastases. area correction is preferable to body weight correction. JNuc/Med l994;35:l64—l67. Furthermore, as an additional diagnostic tool in 360 patients 8. Bilger K. Effects ofobject size and nonuniformity resolution on quantitative measure ments with a new PET Scanner. PhD thesis, University of Tuebingen; 1995. with nonthyroid cancer tumors, 18FDG whole-body PET de 9. Feine U, Lietzenmayer R, Müller-SchauenburgW, et al. Fluorine-l8-FDG whole-body tected benign thyroid adenomas in five patients. There was PET in differentiated thyroid carcinoma. I995;34:l27—134.

ALTERNATINGFLUORINE-18-FDG AND IODINE-131 IODIDEUPTAKEIN THYROIDCANCER•Feine et al. 1471 10. Bloom AD, Adler LP, 5huck JM. Determination ofmalignancy ofthyroid nodules with 13. Sisson JC, Ackermann Ri, Meyer MA, WahI RL. Uptake of “F-fluoro-2-deoxy-d- positron emission tomography. Surgery 1993;I 14:728—735. glucose by thyroid cancer: implications for diagnosis and therapy. J C/in Endocrino/ 11. Voth E, BömerAR, Theissen P. Schicha H. Positron emission tomography (PET) in Metab I993;77:l090—1094. benign thyroid diseases. Exp C/in Endocrinol l994;I02:7l—74. 14. Castillo LA, Yen Pi, Leeper RD. Benia RS. Bone scans in hone metastases from 12. Schmidt D, Herzog H, Langen KJ, Müller-GärtnerHW. Glucose metabolism in thyroid functioning thyroid carcinoma. C/in Nuc/ Med l980;5:20I—206. cancer metastases: a pilot study using ‘F-fluoro-2-deoxyglucoseand positron emis 15. DiChiro G. Positron emission tomography using “F-fluorodeoxyglucose in brain sion tomography. Exp C/in Endocrinol 1994;102:51—54. tumors: a powerful diagnostic and prognostic tool. Invest Radio/ l987;22:360—37l. Comparison of Fluorine- 18-Fluorodeoxygluco se and Carbon-11-Methionine PET in Detection of Malignant Tumors Tomio Inoue, E. Edmund Kim, Franklin C.L. Wong, David J. Yang, Pedro Bassa, Wai-Hoi Wong, Meliha Korkmaz, Wayne Tansey, Keri Hicks and Donald A. Podoloff Departments ofNuclear'Medicine and Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas; Gunma University School ofMedicine, Maebashi, Japan; Hospital Clinic de Barcelona, University School of Medicine, Barcelona, Spain; and University ofAnkara, Ankara, Turkey

malignant tumors is primarily related to its increased transport Two commonly used tumor-seeking agents for PET are 2-deoxy-2- system (4). These different mechanisms of FIX) and Met may 18F-fiuoro-D-glucose (FDG) and L-methyP1C-methknine (Met). provide a different role for clinical PET in detecting various This study compared FDG and Met in detecting residual or recurrent malignant tumors inthe same patients. Methods Thirty-four lesions malignant tumors with different metabolic or biologic behavior. in 24 patients with clink@aIIysuspected recurrentor residualtumors Only a few clinical studies, however, have compared FDG and were studied with PET using Met as well as FOG. FDG scans were Met in detecting untreated tumor (5,6). The present study com cOndUCted 1 hr after the completion of PET with Met. The color pared FDG and Met as tumor-detecting tracers in detecting coded superimposed images of standardized uptake values (SUVs) malignant residual or recurrenttumors in the same patients. and transmission data were produced, and the peak SINs in the lesions were then evaluated. Lesions above 2.5 SUV were inter MATERIALS AND METhODS preted as positive results for active tumor. Results The sensitivity of FOG-PET and Met-PET were 64.5% (20/31 lesions) and 61.3% P@enta (19/31 lesions), respectively. The mean SIN of FDG in residual or Twenty-four patients (14 women, 10 men; aged 19—74yr) were recurrent malignant tumors (n = 31) was signfficanfly higher than treatedfor malignant tumors before the PET study and are included that of Met but there was a significant corralalion (r = 0.788, p < in this study. Pathological diagnoses of the primary tumor were 0.01) between FDG and Met SUVs in all lesions (n = 34). established in all patients: 7 of24 patients had breast cancer; 9 had Conclusion: PET using FDG and Met appear equally effective in malignant soft-tissue tumors; 3 had lung cancer, 3 had bone tumor; detecting residual or recurrent malignant tumors although FDG 1 had colon cancer and 1 had ovarian cancer. Treatmentconducted uptakes were Slightly higher than Met uptakes. Both showed a before the PET study was as follows: 10 patients had systemic limited diagnostic sensitivity for small (<1 .5 cm) tumors. chemotherapy; 5 surgery and systemic chemotherapy, 5 surgery, Key Words PET; fiuorine-18-FDG; carbon-i i-methionine; recurrent systemic chemotherapy and radiation therapy; 2 surgery and tumor radiation therapy; 1 surgery alone, and 1 radiation therapy alone. JNuclMedl99637:1472—1476 Since one patient (Patient 23) had repeated the PET study, 25 PET studies in 24 patients were analyzed and 34 lesions were evaluated (3 1 lesions were recurrent or residual malignant tumors; 26 of them Recentdevelopmentofhigh-resolutionimagingmodalities,were diagnosed based on pathological findings and 5 were diag such as CT, MRI and ultrasonography, has contributed to the nosed based on follow-up clinical findings including tumor marker early detection of malignant tumors because of the precise levels and radiographic evidence of disease progression). Three morphological information about the lesion and surrounding lesions in three patients were non-malignant tumors; one was normal tissue. These noninvasive modalities, however, often diagnosed based on pathological findings and the other two cannot provide helpful information in detecting recurrent or diagnosed based on results of follow-up clinical and radiological residual tumors because of their limitation in differentiating examinations performed for more than 2 yr. recurrent or residual tumors from post-treatment changes (1). Only one patient (Patient 23) had diabetes mellitus and his blood On the other hand, PET with tumor-seeking agents may glucose level was well controlled during the PET study. provide useful functional or biologic information of tumors, especially regarding viable tumor cells or cell proliferation (2). PET Imaging The most widely used tumor-seeking agent with PET is 2-'8F- FDG was produced in the cyclotron facility at The University of fluoro-deoxy-D-glucose (FDG). This agent is transported, phos Texas M.D. Anderson Cancer Center by proton irradiation of enriched phoiylated and metabolically trapped into tumor cells as a glucose ‘8O-waterin a low-volume titanium target. 2-Deoxy-D-glucose was substitute (3). L-methyl-11C-methionine (Met) is an also widely labeled with ‘8Fto produce FDG by the Hamacher method (7) using used tumor-seeking agent for PET studies, which reflects the an automatedsystem developed in our institute.Carbon-l1-Met was amino acid metabolism in tumors. The accumulation of Met in also produced by an automated system developed at our cyclotron @ facility and ‘CO2was produced by a ‘4N(p,a)' ‘Creaction and then Received Aug. 25, 1995; revision accepted Dec. 13, 1995. trapped with liquid nitrogen. From a series of chemical reactions, Forcorrespondence @reprintscont@tE. Edmund Kim,MD,Department of Nuclear Med@ine, The University of Texas M.D. Mderson Cancer Centar, 1515 Holcombe ‘‘CO2was converted to methyliodine, ‘‘CH3Iand then reacted with Blvd., Box 59, Houston TX77030. homocystein to produce ‘‘C-Met.

1472 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 9 . September 1996