Brain lesions: PET/CT. Paolo Castellucci. Medicina Nucleare, Azienda Ospedaliero- Universitaria di Bologna Policlinico S.

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1 Brain lesions: PET/CT Paolo Castellucci Medicina Nucleare, Azienda Ospedaliero- Universitaria di Bologna Policlinico S.Orsola- Malpighi Reggio Emilia 17 aprile 2010

2 MR is the Imaging of choice in brain lesions. However, in some applications the accuracy of MR is limited: 1) Grading 2) Guide biopsy 3) Detect the presence of relapse after surgery and /or RT 4) Monitoring therapy & prognosticate PET (with different radiopharmaceuticals) is an imaging method potentially useful in case of inconclusive findings at MR. REMEMBER: MR is the imaging method of choice!

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4 Brain PET/CT: 1. Grading clinical applications 2. Guide stereotactic biopsy 3. Suspect of relapse after surgery and /or RT. 4. PET-guided contouring for RT 5 Monitoring therapy 6. Prognosticate

5 33 newly diagnosed glioma. LAT1 expression was higher in high grade gliomas. LAT1 expression was correlated with SUVmax

6 Grading ACE MET FDG

7 Grading

8 Grade III astrocyt

9 Grading Brain lesion: not biopsied Choline uptake suggestive for an high grade lesion. = grade IV astroc.

10 Grading MET pos t/b ratio = 4 = Grade IV ASTROCYTOMA

11 Grading MR: uncertain finding (cortical dysplasia vs low grade tumour) MET neg t/b ratio 0.8 = Dysplasia

12 Grading FDG NEG MET POS = Astroc. low grade II

13 18 F-FDG: DELAYED IMAGES 19 pts Astrocytoma Glioblastoma multiforme Glioma

14 Brain PET/CT: clinical applications 1. Grading 2. Guide for stereotactic biopsy 3. Suspect of relapse after surgery and /or RT. 4. PET guided contouring for RT 5 Therapy response evaluation 6 Prognostic informations

15 57 biopsies in 14 patients guided by 18F-FLT PET PET guided biopsy

16 PET guided biopsy Uptake 12 MIB1= 54% it could be particularly useful to grade gliomas Uptake 22 MIB1= 72% Uptake 5 MIB1= 6% Grade III astroc.

17 21 patients with uncharacterized brain lesions studied with FDG and FET PET guided biopsy

18 PET guided biopsy FET sensitivity 93%, specificity 100%, accuracy 96%, PPV 100% NPV 91%. FDG sensitivity 27%, specificity 90%, accuracy 52%, PPV 80% NPV 45%. FET PET is more accurate than FDG PET for detecting malignant brain lesions, especially low-grade gliomas. FET-PET could be particularly useful to guide biopsy but not for grading since it was positive in most of low grade gliomas (7/8)

19 PET/CT: clinical applications 1. Grading 2. Guide for stereotactic biopsy 3. Suspect of relapse after surgery and /or RT. 4. Therapy response evaluation 5. Prognostic informations

20 Suspect of relapse after surgery and /or RT.

21 Suspect of relapse after surgery and /or RT.

22 Suspect of relapse after surgery and /or RT.

23 MET neg for relapse t/b ratio = 0.7

24 Suspect of relapse after surgery and /or RT. MET pos for relapse t/b ratio = 1.5

25 Suspect of relapse after surgery and /or RT. Glioblastoma. RM: inconclusive MET PET: relapse t/b ratio = 2.0

26 Suspect of relapse after surgery and /or RT. MET pos t/b ratio =4.0

27 Suspect of relapse after surgery and /or RT. 11 C-METH FDG: neg MET: relapse 18 F-FDG

28 Suspect of relapse after surgery and /or RT. 11 C-CHOLINE 18 FDG P.V. 68 yo Oligodendroglioma treated with surgery and RT MR: suspected relapse but inconclusive

29 Suspect of relapse after surgery and /or RT. Metastatic lesions from breast ca

30 Brain PET/CT: 1. Grading clinical applications 2. Guide for stereotactic biopsy 3. Suspect of relapse after surgery and /or RT. 4. PET guided contouring for RT 5 Therapy response evaluation 6. Prognostic informations

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32 Fig. 6 Gadolinium-enhanced T1-weighted MRI (a), corresponding 18F-FET PET (b) and fused PET/MR (c) transaxial slices of a clinical study with a glioblastoma showing differences in target volume definition. Indicated are d the GTV delineated on MRI (GTVMRI) and e enhanced details of PET-based BTVs obtained by manual delineation of contours (BTVman; magenta), an isocontour of a SUV of 2.5 (BTV2.5; purple), a fixed threshold of 40% (BTV40%; green) and 50% (BTV50%; cyan) of the maximum signal intensity, SBR-based adaptive thresholding (BTVSBR; yellow), gradient find (BTVGF; blue) and RG (BTVRG; red) segmentation algorithms. Note that GTVMRI overestimates the tumour extension relative to BTVman.

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34 Brain PET/CT: clinical applications 1. Grading 2. Guide for stereotactic biopsy 3. Suspect of relapse after surgery and /or RT. 4. PET guided contouring for RT 5 Therapy response evaluation 6 Prognostic informations

35 Monitoring therapy and prognostic informations

36 Monitoring therapy and prognostic informations 11 C-methionine PET as a prognostic marker in patients with glioma: comparison with 18 F-FDG PET Sungeun Kim 1, 2, June-Key Chung 1, 2, So-Hyang Im 3, Jae Min Jeong 1, 2, Dong Soo Lee 1, Dong Gyu Kim 3, Hee Won Jung 3 and Myung Chul Lee 1 Eur J Nucl Med Mol Imaging, 2004 Aug gliomas RM, FDG-PET, MET-PET MET Uptake is an independnt prognostic factor

37 Monitoring therapy and prognostic informations 11 C-methionine PET as a prognostic marker in patients with glioma: comparison with 18 F-FDG PET Sungeun Kim 1, 2, June-Key Chung 1, 2, So-Hyang Im 3, Jae Min Jeong 1, 2, Dong Soo Lee 1, Dong Gyu Kim 3, Hee Won Jung 3 and Myung Chul Lee 1 Eur J Nucl Med Mol Imaging, 2004 Aug 10

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39 68Ga-DOTA-NOC PET /CT NET tail of the pancreas (arrow) and incidental finding of a MENINGIOMA (unknown)

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43 Brain PET/CT: in summary: clinical applications 1) MET, FLT, FET, CHOL and Acetate are more accurate than FDG in grading gliomas. For this purpose FLT gave very promising results. 2) FLT, FET and MET showed good sensitivity either for low or high grade gliomas, so they can be used mainly to guide biopsy 4) MET showed good sensitivity in detectd replapse, but this is not optimal (75%) 5) MET can provide prognostic information and is usefull to monitor therapy response 6) PET guided RT in brain cancers could be particularly usefull in order to administer a boost were it is evident an increase uptake.

44 IN CONCLUSION Main clinical applications of brain PET are: Grading Guide biopsy Guide RT Detect relapse after surgery or RT Monitoring therapy Prognosticate

45 18 F-FDG Because of the high rate of physiologic glucose metabolism in normal brain tissue, the detectability of tumors with only modest increases in glucose metabolism, such as low-grade tumors and in some cases recurrent highgrade tumors, is difficult. 18F-FDG uptake in low-grade tumors is usually similar to that in normal white matter, and uptake in high-grade tumors can be less than or similar to that in normal gray matter, thus decreasing the sensitivity of lesion detection Grey matter White matter glioblastoma oligodendro glioma

46 18F-FDG Delayed Imaging. Early studies reported enhanced detection of brain tumors with glucose loading, with a 27% increase in the 18F-FDG uptake ratio of tumor to normal gray matter (ref1). However, glucose loading can be difficult to perform clinically because of the need for intravenous glucose infusion and blood glucose monitoring. Recently, an interesting study showed that 18F-FDG imaging 3 8 h after injection can improve the distinction between tumor and normal gray matter (ref2)

47 Indice prognostico

48 PET guided biopsy 32 with glioma 32/32 MET-PET positive 70 biopsies: 61 diagnostic (MET POS) 9 non diagnostic (MET NEG)

49 33 newly diagnosed glioma. LAT1 expression was higher in high grade gliomas. LAT1 expression was correlated with SUVmax

50 21 patients with uncharacterized brain lesions studied with FDG and FET FET-PET could be particularly useful to guide biopsy but not for grading since it was positive in most of low grade gliomas (7/8)

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52 Suspect of relapse after surgery and /or RT... and FDG??? Radiol Clin North Am Jan;43(1): As a general rule, suspicious lesions on MR imaging that show increased FDG uptake are likely to represent tumor recurrence. Sensitivity is low, especially but not exclusively with low-grade gliomas, It seems clear that only the combination of FDG with MET can provide a comprehensive characterization of suspected brain tumor recurrence. Delayed images could help in the diagnosis

53 PET guided biopsy REMEMBER: in small lesions PET (regardless the radiopharmaceutical used) can be FN: Multifocal recurrent glioblastoma FN at FDG and FET

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55 Monitoring therapy and prognostic informations grading Fig. 3a,b MRI, MET PET and FDG PET images of patients with glioma. a MET PET shows hypermetabolism (uptake ratio =4.98), but FDG PET shows iso- /hypometabolism (uptake ratio =0.94). Pathology was glioblastoma, and the Ki-67 index of this tumour was 40%. The patient died 14 months later, a short survival time. relapse b Sixty-one-year-old man with a history of low-grade glioma treated by local resection and chemotherapy. MRI demonstrates residual non-enhancing tumour in the right insular region. FDG PET demonstrates hypometabolism (uptake ratio=0.58) similar to that of white matter, consistent with lowgrade glioma. MET PET demonstrates a focal area of hypermetabolism (uptake ratio =3.97). This area was confirmed as anaplastic transformation with a relatively higher proliferative index (Ki-67 index=20%) at stereotactic biopsy

56 Grading MR inconclusive MET negative? t/b ratio= 1.4 = Astroc. Low grade II