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O R I G I N A L A R T I C L EAnnals of Nuclear Medicine Vol . 21, No. 2, 129-135, 2007

D i a g n o s i s o f m a x i l l o f a c ia l t u m o r w i t h L - 3 - [l S F ] - fl u o r o - tz - m e t h y l t y r o s in eF M T ) P E T : a c o m p a r a t i v e s tu d y w i th F D G - P E T

M itsu yu ki MIYAKUBO, , N o b o r u ORIUCHI, Y o s h i t o TSUSHIMA, T et su y a HIGUCHI, K e i k o KOYAMA,K iyo ka zu ARAI, Bish nuh ari PAUDYAL, Y a s u h i k o IIDA, H irof um i HANAOKA, T o m o h i r o ISHIKITA,Y os hi ki NAKASONE, A k i h i d e NEGISHI, K e n j i i O G l * a n d K e i g o E ND O **

Department of Stomatology and Maxillofacial Surgery;Department of Diagnostic Radiology and Nuclear Medicine;Department of Bioimaging Information Analysis;21st Century COE program, Gunma University Graduate School of Medicine

Objectives: T o c o m p a r e L - 3 -[ 1 8 F ]- f lu o r o - tz - m e t hy l ty r o s in e F M T ) - p o s i t r o n e m i s s i o n t o m o g r a p h yP E T ) a n d 2 - [ 1 8 F ] - fl u o r o - 2 - d e o x y - D - g l u c o s e F D G ) - P E T in t h e d i f f e r e n t i a l d i a g n o s i s o f m a x i l l o -f a c i a l t u m o r s . Methods: T h i s st u d y in c l u d e d 3 6 p a t i e n t s 1 6 m a l e s , 2 0 f e m a l e s ; 3 1 - 9 0 y e a r s o l d )

w i t h u n tr e a t e d m a l i g n a n t t u m o r s 3 4 s q u a m o u s c e ll c a r c i n o m a , o n e m u c o e p i d e r m o i d c a r c in o m a ,o n e r h a b d o m y o s a r c o m a ) a n d s ev e n p a ti e n ts f iv e m a l e s , tw o f e m a l e s ; 3 2 - 8 1 y e a r s o ld ) w i t h b en i g nl e s i o n s . I n a l l p a t i e n t s , b o t h F M T - P E T a n d F D G - P E T w e r e p e r f o r m e d w i t h i n t w o w e e k s b e f o r eb i o p s y o r t r e a t m e n t o f th e l es i o ns . T o e v a l u a t e t h e d i a g n o s t ic u s e f u l n e s s o f F M T - P E T a n d F D G -P E T , v i s u a l i n t er p r e ta t io n a n d s e m i q u a n t i t a t iv e a n a l y s i s w e r e p e r f o r m e d . P E T i m a g e s w e r e r a t e da c c o r d i n g t o th e c o n t r a s t o f t u m o r u p t a k e a s c o m p a r e d w i t h b a c k g r o u n d , a n d w e r e s t a ti s ti c a ll ya n a l y z e d . A s a s e m i q u a n t i t a t i v e a n a l y s i s , s t a n d a r d i z e d u p t a k e v a l u e s S U V ) o f th e p r i m a r y t u m o r sw e r e m e a s u r e d , a n d t h e S U V d a t a w e r e a n a l y z e d u s i n g r e c e i v e r o p e r a t i n g c h a r a c te r i s ti c R O C )c u r v e s . Results: The m e a n S U V o f th e m a l i g n a n t l e s i o n s w e r e s i g n i f ic a n t l y h i g h e r t h a n t h o s e o f t h eb e n i g n l e s i o n s i n b o th F M T - P E T 2 . 6 2 + 1 . 58 v s . 1 .2 0 + 0 . 30 , p < 0 . 0 1 ) a n d F D G - P E T 9 . 1 7 + 5 . 0 6vs . 3 .14 + 1 .34 , p < 0 .01) . A pos i t i ve cor r e l a t i on r = 0 .567 , p < 0 .0001 , n = 46) w as no t ed be t wee nF M T a n d F D G . R O C a n a l y s i s r e v e a l e d th a t th e r e w a s n o s t a ti s ti c a l ly s i g n i f ic a n t d i f f e r e n c e in S U V sb e t w e e n F M T a n d F D G f o r d if f e re n t ia t i n g m a l i g n a n t t u m o r s . In 2 7 o f 3 6 p a ti e n ts , F M T - P E T h a db e t t e r c o n t r a s t o f m a l i g n a n t t u m o r v i s u a l iz a t i o n t o t h e s u r r o u n d i n g n o r m a l s t r u c t u r e s b y v i s u a la s s e s s m e n t p < 0 . 0 0 5 , b i n o m i a l p r o p o r t i o n t es t ). Conclusions: D i f f er e n ti a l d i ag n o s i s o f F M T - P E Tb a s e d o n t h e u p t a k e i n m a x i l l o fa c i a l t u m o r s i s e q u iv a l e n t t o F D G - P E T . H o w e v e r , t h e c o n t ra s t o fF M T u p t a k e b e t w e e n m a x i l l o f a c ia l t u m o r s a n d t h e s u r r o u n d i n g n o r m a l s t r u c tu r e s i s h i g h e r t h a n th a to f F D G , i n d i c a ti n g t h e p o s s ib i l it y o f a c c u r a t e d i a g n o s i s o f m a x i l l o f a c i a l t u m o r s b y F M T - P E T .ey w o r d s : L - 3 - [ 1 8 F ] -f l u o r o -t x - m e t h y lt y r o s in e F M T ) , 2 - [ 1 8 F ] - f lu o r o - 2 - d e o x y - D - g l u c o s e F D G ) ,

m a x i l l o f a c i a l t u m o r , P E T

Rece i ved No vem ber 24 , 2006, r ev i s ion accep ted Decem ber27, 2006.

For repr int contact : N obo ru Or iuchi, M.D. , Ph.D. , De par t -ment o f D i agnos t i c Rad i o l ogy and Nuc l ea r M edic ine , Gun maU n i v e r s it y G r a d u a t e S c h o o l o f M e d i c in e , 3 - 3 9 - 2 2 S h o w a -machi , Maebashi , Gunma 371-8511, JAPAN.E-mai l : or iuchi @showa .gunma- u .ac . j p

I N T R O D U C T I O NMAXILLOFACIALTU MO R i s u s u a l l y f o u n d b y p h y s i c a l e x -a m i n a t i o n ; h o w e v e r , i t i s s o m e t i m e s d i f f i c u l t t o e v a l u a t ee x a c t l y t h e e x t e n t a n d m a l i g n a n c y o f th e d i se a s e . S i n c et h e h e a d a n d n e c k a r e a i n v o l v e s c o m p l i c a t e d a n a t o m i c a ls t r u c t u r e s a n d i m p o r t a n t f u n c t i o n s s u c h a s m a s t i c a t i o na n d p h o n a t i o n , i t is n e c e s s a r y t o p r e s e r v e t h e m o r p h o l o g ya n d f u n c t i o n a s m u c h a s p o s s i b l e w h i l e t ry i n g t o m a x i -m i z e t h e e f f e c t i v e n e s s o f t h e s u r g i c a l t r e a t m e n t .

Vol. 21, No . 2, 2007 Original Article 129


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A l t h o u g h 2 - [ 1 8 F ] - f l u o r o - 2 - d e o x y - D - g l u c o s e ( F D G ) -p o s i t r o n e m i s s i o n t o m o g r a p h y ( P E T ) i s a u s e f u l i m a g i n gt o o l t o e v a l u a t e t h e m a l i g n a n c y o f m a x i l l o f a c i a l t u m o r s ,a c c u m u l a t i o n i n n o r m a l o r g a n s a n d n o n - s p e c i fi c u p t a k e i nb e n i g n l e s i o n s a r e c o m m o n . L 2 L - 3 - [ 18 F ] - F lu o r o - o t- m e t hy l t y r o si n e ( F M T ) - P E T w a s d e v e l o p e d i n o u r i n s t i tu t ea n d s h o w e d h i g h s p e c i f ic i t y f o r s e v e r a l m a l i g n a n t t u m o r sa s c o m p a r e d w i t h F D G - P E T . 3 -5 I n t h e p r e s e n t s t u d y , w ec o m p a r e d t h e d i a g n o st i c a b i li t y o f F M T - P E T a n d F D G -P E T f o r th e d i a g n o s i s o f m a x i l l o f a c i a l t u m o r s .

M T E R I L S N D M E T H O D S

PatientsC o n s e c u t i v e 4 3 p a t i e n t s w i t h u n t r e a t e d m a x i l l o f a c i a l tu -m o r w h o u n d e r w e n t P E T s t u dy b e t w e en M a y 1 9 99 a n dJ u l y 2 0 0 6 w e r e a n a l y z e d . T h e s t u d y i n c l u d e d 3 6 p a t i e n t s( 1 6 m a l es , 2 0 f e m a l e s ; a g e r an g e , 3 1 - 9 0 y e a r s o l d ) w i t hm a l i g n a n t tu m o r s ( 3 4 s q u a m o u s c e l l c a r c i n o m a [ S C C ] ,o n e m u c o e p i d e rm o i d c a r c in o m a , o n e r h a b d o m y o s a r c o m a )a n d s e v e n p a t i e n t s ( f i v e m a l e s , t w o f e m a l e s ; a g e r a n g e ,3 2 - 8 1 y e a r s o l d ) w i t h b e n i g n m a x i l l o f a c i a l l e s io n s . T h r e ep a t i e n t s w i t h m a l i g n a n t t u m o r s a l s o h a d b e n i g n l e s i o n s ,a n d t h u s t e n b e n i g n l e s i o n s ( f o u r d e n t a l c y st s , o n e a m e l o -b l a st o m a , o n e s c h w a n n o m a , o n e p a p i l l o m a , o n e h e m a n -g i o m a , o n e f i b r o m a , o n e i n f l a m m a t o r y m a s s l e s io n ) w e r einc luded in th i s s tudy .

H i s t o p a t h o l o g i c a l d i a g n o s i s o f th e p r i m a r y l e s i o n w a se s t a b li s h e d w i t h s p e c i m e n s o b t a i n e d b y b i o p s y o r s u r g i c a lr e s e c t io n . A l l r e s e c t e d t i s s u e s w e r e e x a c t l y l o c a l i z e d a n dd o c u m e n t e d a t e a c h l e v e l t o a l l o w c o r r e l a ti o n b e t w e e n t h eh i s topa tho log ic f ind ings and the p reopera t ive P ET f ind ings .S t a g in g o f t h e p r i m a r y t u m o r a n d r e g i o n a l l y m p h n o d em e t a s t a s is w a s b a s e d o n t h e T N M s y s t e m . 6 H i s t o p a t h o -l o g i c a l a n a l y s i s r e v e a l e d c e r v i c a l l y m p h n o d e m e t a s t a s e si n t 0 p a t i en t s . A b s e n c e o f c e r v i c a l l y m p h n o d e s m e t a s t a -s is w a s d e t e r m i n e d b y t h e c l i n i c a l fo l l o w - u p f o r m o r e t h a ns ix m o n t h s i n c l u d in g i m a g i n g s u c h a s c o m p u t e d t o m o g -r a p h y ( C T ) a n d / o r m a g n e t i c r e s o n a n c e i m a g i n g ( M R I ) . I na l l p a t i e n t s , b o t h F M T - P E T a n d F D G - P E T w e r e p e r -f o r m e d w i t h i n t w o w e e k s b e f o r e b i o p s y o r t r e a tm e n t , a n dc o n t r a s t - e n h a n c e d C T a n d M R I w e r e a l s o p e r f o r m e dd u r i n g t h e s a m e p e r i o d .

T h i s s t u d y w a s a p p r o v e d b y t h e I n s t it u t io n a l R e v i e wB o a r d o f o u r i n s ti t u te , a n d a l l t h e p a t i e n ts g a v e i n f o r m e dconsen t .Radiopharmaceu t ica l sF M T a n d F D G w e r e p r o d u c e d i n o u r c y c l o t r o n fa c i l it y .F M T w a s s y n t h e s i ze d b y t h e m e t h o d d e v e l o p e d b yT o m i y o s h i w i t h a d e d i c a t e d a p p a r a t u s a s r e p o r t e d p r e v i -ous ly .7 F D G w a s s y n t h e s i ze d b y t h e m e t h o d d e v e l o p e d b yI d o 8 a n d H a m a c h e r 9 w i t h a n a u t o m a t e d a p p a r a tu s . T h eq u a l it y o f F M T a n d F D G w a s t e s t e d f o r s t e ri l it y , p y r o -g e n i c i t y , a n d r a d i o c h e m i c a l p u r i t y o n e a c h r u n .

P E T i ma g i n gP E T i m a g e s w e r e o b t a i n e d w i t h a d e d i c a t e d w h o l e - b o d yP E T s c a n n e r S E T 2 4 0 0 W ( S h i m a d z u C o r p o r a ti o n , K y o t o ,J a p a n ) w i t h a 5 9 . 5 - c m t r a n s a x i a l f i e ld o f v i e w a n d 2 0 - c ma x i a l f i e ld o f v i e w w h i c h p r o d u c e d 6 3 i m a g e p l a n e ss p a c e d 3 . 1 2 5 m m a p a r t . T r a n s a x i a l s p a t i a l r e s o lu t i o n w a s4 . 2 m m f u l l w i d t h a t h a l f m a x i m u m ( F W H M ) a t th e c e n t e ro f t h e f ie l d o f v i e w a n d a x i a l r e s o l u t i o n w a s 5 . 0 m mF W H M . D a t a w e r e a c q u i r e d b y t h e s i m u l ta n e o u s e m i s -s i o n - tr a n s m i s si o n m e t h o d w i t h a r o t a t i n g e x t e r n a l s o u r c e( 68 G e) a t 6 0 m i n a f t e r th e i n j e c t i o n o f 5 - 6 M B q / k g ( b o d yw e i g h t ) . F o u r t o f iv e b e d p o s i t i o n s f r o m t h e h e a d t o t h et h i g h w e r e a c q u i r e d f o r 8 m i n p e r b e d p o s i t io n . P a t i e n t sf a s t e d f o r a t l e a s t 6 h o u r s b e f o r e t h e P E T s t u d i e s . T h eb l o o d g l u c o s e l e v el a t t h e t i m e o f F D G - P E T i n j e c ti o n w a sle s s than 120 m g/d l in a ll pa t i en t s . The re we re no pa t i en t swi th d iabe te s m e l l i tus in th i s s tudy .

A t t e n u a t i o n - c o r r e c t e d t r a n s a x i a l i m a g e s w i t h F M T a n dF D G - P E T w e r e r e c o n s t r u c t e d b y t h e o r d e r e d su b s et e x -p e c t a t i o n m a x i m i z a t i o n a l g o r i t h m i n t o 1 2 8 x 1 28 m a t r i-c e s w i t h p i x e l d i m e n s i o n s o f 4 . 0 m m i n t h e t ra n s a x i alp l a n e a n d 3 . 1 2 5 m m i n t h e a x i a l d i r e c t i o n . F o r t h e v i s u ali n t e r p r e t a t io n a n d s e m i q u a n t i t a t i v e a n a l y s i s , 3 c o n s e c u -t i v e sl i c es w e r e a d d e d t o g e n e r a t e t r a n s a x i a l i m a g e s w i t h9 . 8 m m t h i c k n e ss . C o r o n a l i m a g e s w i t h 9 . 8 m m t h i ck n e s sw e r e a s o r e c o n s t r u c t e d f o r t h e i m a g e i n t e r p r e ta t i o n .Quali ta tive assessmen t o f PE T image sP E T i m a g e s w e r e v i s u a l l y i n t e r p r e t e d b y t w o n u c l e a rm e d i c i n e p h y s i c i a n s . T h e y e v a l u a t e d t h e u p t a k e o f t r a c e ri n th e l e s io n s a s c o m p a r e d w i t h t h e s u r r o u n d i n g n o r m a ls t ru c t u re s , b a s ed o n t h e k n o w l e d g e t h a t n o r m a l o r g a n ssuch a s m usc le s , tons i l s, tong ue an d s a l iva ly g lands som e-t i m e s s h o w h i g h u p t a k e o f F D G . T h e r e f o r e , e ac h u p t a k ei s ca re fu l ly in te rpre ted a s to w he th e r i t is abnorm al o r no t .T h e n t h e s u p e ri o r it y o f F M T a n d F D G i m a g e s w a s r a te da c c o r d i n g t o t h e c o n t r a s t o f u p t a k e i n t h e l e s i o n a s c o m -p a r e d w i t h t h e u p ta k e i n t h e b a c k g r o u n d .S e mi q ua n t it a ti v e a s s e s s me n t o f P E T i ma g e sP E T i m a g e s w e r e s e m i q u a n t i t a t i v e l y a n a l y z e d u s i ng t h es t a n d a r d iz e d u p t a k e v a l u e ( S U V ) w h i c h w a s c a l c u la t e d a sf o l l o w s :

S U V = R a d i o a c t i v i t y i n t h e t i s su e o r l e s i o n ( M B q / g )I n j e ct e d d o s e ( M B q ) / p a t i e n t ' s b o d y w e i g h t ( g )

A r e g i o n o f i n te r e s t ( R O I ) w a s c a r e f u l l y d r a w n o n t h ea ' ansax ia l im age , wh ich sh ow s the h igh es t rad ioac t iv i ty int h e t u m o r . W h e n t h e a b n o r m a l u p t a k e i s n o t d e m a r c a t e di n t h e l e s io n , C T o r M R I i m a g e s w e r e u s e d a s a r e f e r e n c et o d r a w a n R O I .Stat is t ical analysisS t a t i s t i c a l a n a l y s i s w a s p e r f o r m e d u s i n g S t a t V i e w( A b a c u s C o n c e p t s , U S A ) . T h e c o n t r a s t o f u p t ak e d e t e r -m i n e d b y t h e v is u a l i n t e rp r e t a t i o n w a s c o m p a r e d u s i n g

130 Mitsuyuki Miyakubo, No boru Oriuchi, Yosh ito Tsushima, et al nnals o f Nuclear Medicine


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Fig, 1 A 78-year-old female with well differenti atedsquamous cell carcinoma of the left maxilla. A, Contrast-enhanced CT scan demonstrates a primary lesion arrow).B, Specimen of the primary lesion. C, FMT-PET imageshows high uptake SUVmax. = 3.74) only in the primarylesion arrow). D, FDG-PET image shows high uptakeSUVmax. = 8.94) in the primary lesion arrow).

A. Contrast-enhanced CT J B. SpecimenC. FMT-PET / D. FDG-PET

f A. Contrast enhancedT~ SpecimenC. FMT -PET FDG-PET

Fig . 2 A 31 -year-o ld male with rhabdomyosarcoma in the rightbuccal region alveolar type). A, Contrast-enhanced CT scandemonstrates the primary lesion arrow). B, Specimen of theprimary lesion. C, FMT-PET image shows high uptake SUVmax.= 2.99) only in the primary lesion arrow). D, FDG-PET imageshows high uptake SUVmax. = 5.64) in the primary lesionarrow), and also shows high to moderate uptake in tonsils,

tongue, and other normal structures.

AI Contrast-enhancedC'[ B. Specimen IFMT-PET I D. FDG-PET

Fig. 3 A 43-year-old female with benign ametobtastoma of theleft mandible plexiform type). A, Contrast- enhanced CT scandemonstrates a primary lesion arrow). B, Specimen of theprimary lesion. C, FMT-PET image shows slightly increaseduptake SUVmax. = 1.16) in the benign tumor arrow). D, FDG-PET image shows high uptake SUVmax. = 5.44) in the primarylesion arrow), and also shows high to moderate uptake in thetonsils, suprahyoid muscles, and other normal structures.

Vol. 21, No. 2, 2007 Original Article 131


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8

II

0

Q8o

gA Benign lesion Malignant tumors

[1.20'r lmeam_+S.D.1 n= 10 , 2.62 a=361

25

2O

v

5

o8oo8B

ooo

B Benign esion Malignant tumorsf3. 14r Imeam.cS.D.l n=10 ) 1 9.17:t.5.06 mesac S.D.l n=36)

F i g 4 SUV for FMT and FDG in the primary lesions. Plots showthe maximum SUVs of A) FMT and B) FDG. A significantdifference in SUVs between the two groups is observed withFMT-PET and FDG-PET. SUV of malignant lesions wassignificantly higher than that of benign lesions FMT; 1.20 +0.30 vs. 2.62 + 1.58, p < 0.01. FDG; 3.14 +_ 1.34 vs. 9.17 + 5.06,p < 0.01).the bin omial proport ion test. I~ Quantitative parameters(SUVmax.) were assessed using receiver operating char-acteristic (ROC) curves (Rockit 0.9B; C. E. Metz, Univer-sity of Chicago, 1998). II Z-statistics was also used. A p-value o f less than 0.05 was con sidered significant.

R E S U L T S

isual evaluationUptake of FMT in the lesions were correlated with theuptake of FDG. In 36 patients with malignant lesions,FMT-PE T had better contrast of tumor visualization to thesurrounding normal structures in 27 patients (75 ). Thebinomial proportion test revealed that the contrast of FMTuptake in the lesion was significantly superior to the FDG(p < 0.005).

Histopathologic examination revealed that 34 of 43patients had SCC. Most of the patients with SCC werepositive for both FMT and FDG-PE T uptake as shown inFigure 1. FMT-PET and FDG-PET showed an abnormaluptake in 30 and 32 of 34 patients with SCC, respectively.

v

I -.=

198765432t

25

n=46r=0.567 op


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Tab l e Results of ROC analysis (primary lesions)Trac er SUV cut -off Sensit ivi ty Spe ci f ic ity A ccuracy PPR NPRFM T 1.45 30/36 (83 ) 8/10 (80 ) 38/46 (83 ) 30/32 (93 ) 8/14 (57 )FD G 4.72 29/36 (81 ) 8/10 (80 ) 37/46 (80 ) 2 9/ 3 1 94 ) 8/15 (53 )

PPR: posit ive predictive ratioNPR : negat ive p redict ive ra tio

T ab l e 2 Com par ison of diagnostic abi l i ty wi th FMT-PE T and FDG -PET for the diagnosisof lym ph node m etastasis by visual interpretationTra ce r Sensitivity Specifici ty Acc uracy PPR NPRFM T 7/10 (70 ) 25/26 (96 ) 32/36 (89 ) 7/8 (88 ) 25/28 (89 )FD G 9/10 (90 ) 21/26 (81 ) 30/36 (83 ) 9/14 (64 ) 21/22 (96 )

PPR: posit ive predictive ratioNPR : negat ive p redict ive ra tio

a n d F D G ( F i g . 5 ) .R O C c u r v e s o f b o th F M T - P E T a n d F D G - P E T a r e

s h o w n i n F i g u r e 6 . C h i - s q u a r e t e s t r e v e a l e d a v a l u e o f 0 .2 8w i t h a c o r r e s p o n d i n g p - v a l u e o f 0 . 8 7 . N o s t a t i s ti c a l lys ig n i fi ca n t d i f f e re n c e w a s o b s e r v e d b e t w e e n F M T - P E Ta n d F D G - P E T r e g a r d i n g d i f f e r e n ti a ti o n o f m a l i g n a n tt u m o r s f r o m b e n i g n l e si o n s. R O C a n a l y s i s d e t e rm i n e dt h a t t h e o p t i m a l c u t - o f f v a lu e o f S U V i n d i f fe r e n t i a ti n gm a l i g n a n t t u m o r s f r o m b e n i g n m a x i l lo f a c i a l l e s io n s u s -i ng F M T a n d F D G w a s 1 .4 5 a n d 4 .7 2 , re s p e c ti v e ly . T a b l e1 s h o w s t h e d i a g n o s t i c p e r f o r m a n c e o f P E T s tu d i es w i t hF M T a n d F D G . T h e r e w a s n o s i g n i f i c a n t d i f f e r e n c e i ns e n s i t i v i t y n o r s p e c i f i c i ty , e v e n i f t h e o p t i m a l c u t - o f fv a lu e s o f S U V w e r e e m p l o y e d .

ymph node and distant metastasisC e r v i c a l l y m p h n o d e s w e r e r e s ec t e d a t t h e t im e o f p r im a r yt u m o r r e s e c ti o n . F o u r t e e n m e t a s ta t i c n o d e s w e r e p a t h o -l o g i c a l l y p r o v e d , a n d o f t h e s e 1 4 n o d e s , 1 1 s h o w e dv i s u a l l y p o s i t i v e u p t a k e o f F M T ( 7 9 ) . I n c o n t r a st , F D G -P E T s h o w e d p o s i t i v e u p t a k e i n 13 o f 1 4 n o d e s ( 9 3 ) .T h e r e w a s n o s i g n if i c a n t d i f fe r e n c e b e t w e e n t h e p o s i ti v er a ti o o f F M T - P E T a n d F D G - P E T f o r d et e ct in g l y m p hn o d e m e t a s t a s i s ( p = 0 . 5 9 6 , F i s h e r ' s e x a c t te s t) . T h e r e w a so n e c a s e w i t h f a l s e p o s i t iv e u p t a k e o f F M T - P E T i n th el y m p h n o d e s ; h o w e v e r , f i v e c a s e s w i th o u t m e t a s t a s i ss h o w e d f a l se p o s i t i v e u p t a k e o f F D G - P E T . D i a g n o s t ica b il it y o f F M T - P E T a n d F D G - P E T f o r l y m p h n o d e m e -t a s t a s is i s s h o w n i n T a b l e 2 .

T w o p a t i e n t s h a d d i s t a n t m e t a s t a s i s i n t h e l un g . B o t hF M T - P E T a n d F D G - P E T c o u l d d e t ec t t h e se l e si o n s b yv i s u a l i n t e r p r e t a t i o n .

D I S C U S S I O NP E T i s a f u n c t i o n a l , n o n - i n v a s i v e i m a g i n g m e t h o d t h a th a s b e e n u s e d f o r t h e d i a g n o s i s o f a v a r i e t y o f c a n c e r si n c l u d i n g m a x i l l o f a c i a l t u m o r s . 12-14 F D G - P E T h a s s h o w n

a c c e p t a b l e a b i l i t y f o r s t a g i n g m a x i l l o f a c i a l t u m o r s . 15H o w e v e r , f a l s e p o s i t i v e f in d i n g s o f F D G - P E T d u e t ou p t a k e in b e n i g n l e s io n s a n d n o r m a l o r g a n s d e c r e a s e t h es p e c i f i c it y f o r t h e d i a g n o s i s o f c a n c e r .

I n o r d e r t o i m p r o v e t h e s p e c i f i c i ty f o r t h e d i a g n o s i s o fh e a d a n d n e c k c a n c e r , r a d i o t r ac e r s o t h e r th a n F D G h a v eb e e n u s e d a s P E T t r a c e r s. 1 6-1 8 H o w e v e r , t h e s e t r a c e r sh a v e n o t b e e n e s t a b l i s h e d f o r c l i n i c a l u s e y e t .

I n t h e p r e s e n t s t u d y , f l u o r i n e - 1 8 - l a b e l e d t y r o s i n e a n a -l o g u e , F M T w a s e v a l u a t e d f o r t h e d i a g n o s t ic a b i l i t y i nm a x i l l o f a c i a l t u m o r s . T h e r e w a s n o s t a t i s t i c a l l y s i g n i f i -c a n t d i f f e r e n c e b e t w e e n F M T - P E T a n d F D G - P E T i nd i f f e r e n t i a t i n g m a l i g n a n t a n d b e n i g n l e s i o n s . H o w e v e r ,t h e l o w e r a c c u m u l a t i o n o f F M T i n th e n o r m a l s t r u c tu r e sa s c o m p a r e d w i t h F D G w a s a n a d v a n t a g e f o r i m a g i n gt u m o r s i n t h e m a x i l l o f a c i a l r e g i o n , b e c a u s e i t m a k e s a na c c u r a t e d e l in e a t i o n o f m a l i g n a n t l e s i o n s a p a r t f r o m t h es u r r o u n d i n g n o r m a l t i ss u e . T h e r e s u l t s o f t h e p r e s e n ts t u d y i n d i c a t e d t h a t th e c o n t r a s t o f t h e F M T u p t a k e i n t h em a l i g n a n t t u m o r s w a s s i g n i f ic a n t ly s u p e r i o r t o F D G .A c c o r d i n g t o a p r e v i o u s s t u d y , 3 t h e w h o l e - b o d y F M T -P E T i m a g e s i n h e a l t h y v o l u n t e e r s s h o w e d h i g h c o n c e n -t r a ti o n s o f r a d i o a c t i v it y i n t h e k i d n e y s a n d u r i n a r y b l a d d e ra n d f a i n t u p t a k e i n t h e b r a i n , l iv e r , c a rd i a c b l o o d p o o l a n ds o f t ti s s u e, b u t t h e s e u p t a k e s w e r e s i g n i f ic a n t l y l e s s t h a nt he u p t a k e s o f F D G . M u s c u l a r u p t a k e o f F M T w a s p a r -t i c u la r l y l o w e r t h a n t h a t o f F D G . 3

T h e p r e c i s e m e c h a n i s m o f th e s e l e c ti v e a c c u m u l a t i o no f F M T i n m a l ig n a n t t u m o r s a n d t h e l o w u p t a k e i n b e n i g nl e s i o n s is n o t f u l l y u n d e r s t o o d . A p r e l i m i n a r y e v a l u a t i o ni n d i c a t e d t h a t t h e e x p r e s s i o n o f L - t y p e a m i n o a c i d t r a n s -p o r t e r ( L A T ) c o u l d c o r r e l a te w i t h t h e m a l i g n a n c y o f t h em a x i l l o f a c i a l t u m o r s . 19 T h e n a t u r a l a m i n o a c i d L - t y r o s in ei s tr a n s p o r te d b y b o t h s u b t y p e 1 a n d s u b t y p e 2 o f L A T . 2 ~A n o t h e r s t u d y d e m o n s t r a t e d t h a t L A T - l i k e tr a n s p o r t m a yo c c u r a c c o r d i n g t o t h e s u b t y p e o f L A T . 21 T h i s t r a n s p o r t e rs u b t y p e , h o w e v e r , d o e s n o t a p p e a r to b e e x p r e s s e d i ni n f l a m m a t o r y t i s s u e . B a s e d o n t h e s e f i n d i n g s u s i n g a

Vol. 21, No. 2, 2007 Original Article 133


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s i m i l a r t r a c e r o f O - ( 2 - [ 1 8 F ] f l u o r o e t h y l) - L - t y r o s in e( F E T ) , 22'23 t he l ow up t a ke o f F M T i n t he no r ma l t i s sue a ndt h e i n f l a m m a t o r y t i s s u e m i g h t b e e x p l a i n e d .

S e v e r a l r e p o r t s h a v e s h o w n t h e h i g h a b i li ty o f F D G -P E T i n d e t e c t i n g c e r v i c a l l y m p h n o d e m e t a s t a s i s . 14,15 I nt h e p r e s e n t st u d y , F M T - P E T c o u l d d e t e c t l y m p h n o d em e t a s t a s i s in 1 1 l es i o n s , a n d F D G - P E T c o u l d d e t e c tm e t a s t a si s in 1 3 l e s io n s ; h o w e v e r , F D G - P E T s h o w e d f i v ef a l s e p o s i t i v e re s u l ts , a n d F M T - P E T s h o w e d o n e f a l sep o s i t i v e r es u l t. A l t h o u g h t h e r e i s n o s i g n i fi c a n t d i f f e r e n c eb e t w e e n F M T - P E T a n d F D G - P E T r e g a rd i n g d ia g n o s ti cp a r a m e t e r s a s s h o w n i n T a b l e 2 , f u r t h e r s t u d i e s a r e r e -q u i r e d t o c o n f i r m t h e d i a g n o s t i c a b i l i ty f o r l y m p h n o d em e t a s t a s i s .

I t i s w e l l k n o w n t h a t F D G - P E T i s u s e f u l to d e t e c td i s t a n t m e t a s t a s i s i n p a t i e n t s w i t h m a x i l l o f a c i a l c a n c e r . 2 4I n th i s st u d y , w e h a d o n l y t w o p a t i e n ts w h o s h o w e dp o s i ti v e u p ta k e o f b o t h F M T - P E T a n d F D G - P E T ind i s t a n t m e t a s t a s i s .

T h i s s t udy had seve r a l l i mi t a t i ons . F i r s t , t he sub j ec t s i nt h is s t u d y h a d a h e t e r o g e n o u s r a n g e o f t u m o r s w i t h f e wb e n i g n n e o p l a s m s , a n d m o s t o f t h e m a l i g n a n t t u m o r s w e r eS C C . I n c a s e o f S C C , F D G - P E T c o u l d d e t e ct m o r e l e si o n s( 3 2 /3 4 , 9 4 ) t h a n F M T - P E T ( 3 0 /3 4 , 8 8 ) b a s e d o n t h ev i s u a l i n t e r p r e t a t i o n . H o w e v e r , p o s i t i v e p r e d i c t i v e r a t i oa n d n e g a t i v e p r e d i c t i v e r a t io o f F M T - P E T ( 3 0 / 3 2 , 9 3a n d 8 /1 4 , 5 7 , r e s p e c ti v e l y ) a n d F D G - P E T ( 29 / 3 1, 9 4a n d 8 / 1 5, 5 3 , r e s p e c t i v e l y ) f o r d e t e c t i n g p r i m a r y t u m o ri n a ll p a t i e n t s w e r e e q u i v a l e n t a n d s h o w e d n o s i g n i f i c a n td i f f e r e n c e b a s e d o n t h e R O C a n a l y s is . S e c o n d , t h e c o n -t r a s t o f t u m o r u p t a k e o f t r a c e r t o t h e n o r m a l s t r u c t u r e s w a sn o t q u a n t i t a t i v e l y m e a s u r e d , b u t v i s u a l l y a s s e s s e d , a l -t h o u g h s t a t i s t i c a l a n a l y s i s r e v e a l e d t h a t F M T - P E T w a sb e t te r th a n F D G - P E T b y t h e v i su a l a s s e ss m e n t . L o w e ru p t a k e o f F M T a s c o m p a r e d w i t h F D G m i g h t d e c re a s e th ed e t e c t a b i l i t y o f s m a l l l e s i o n s . T h e l i m i t e d a v a i l a b i l i ty o fF M T - P E T is a n o t h e r d r a w b a c k .

I n c o n c l u si o n , F M T a n d F D G u p t a k e s in m a l i g n a n tt u m o r s w e r e s i g n i f i c a n t l y h i g h e r t h a n t h o s e i n b e n i g nt u m o r s. B o t h F M T - P E T a n d F D G - P E T c o u l d d i ff e re n ti -a t e b e t w e e n m a l i g n a n t a n d b e n i g n l e si o n s, a n d t h e y w e r ea l m o s t e q u a l l y e f f e c t i v e i n d e t e c t i n g m a x i l l o f a c i a l t u -m o r s . H o w e v e r , F M T - P E T h a d b e t t e r c o n t ra s t b e tw e e nm a l i g n a n t l e s io n s a n d n o r m a l s t ru c t u r es t h a n F D G - P E T ,b e c a u s e F M T u p t a k e i n t h e n o r m a l o r g a n s w a s s i g n i f i -c a n t l y l o w e r t h a n F D G u p t a k e . F u r t h e r i n v e s t i g a t io n t ov e r i f y t h e c li n ic a l u s e f u l n e s s o f F M T - P E T i s e n c o u r a g e di n a v a r i e t y o f t u m o r s w i t h a l a r g e r s e r i e s o f p a t i e n t s .

A C K N O W L E D G M E N TThis wo rk was suppor ted by grants f ro m the Japan Society forthe Promot ion of Science (21st Century COE Prog ram-G unm aUniversi ty). We also thank Dr. Toru Y amaguchi and M s. MayumiTo ma ru for helpful suggestions with respect to pathology.

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c h o l i n e i n d i f f e r e n t i a l d i a g n o s i s o f h e a d a n d n e c k t u m o r s :c o m p a r i s o n w i t h 1 8 F - F D G P E T . nn Nucl Med 2 0 0 4 ; 1 8409- -417 .

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