FDOPA, C11Choline, C11 Methionine. Dr K.G.Kallur

Transcription

1 FDOPA, C11Choline, C11 Methionine Dr K.G.Kallur

2 Why? 11C Methionine scan Had undergone resection Earlier. Post op recurrent hypercalcemia

3 C11 Methionine Unable to see in Sestamibi scan

4 Brain Tumor After treatment questions to be answered Necrosis? Viable tumor? Recurrence? Biopsy site Prognostication

5 Lymphoma

6 Limitations of FDG PET Imaging of brain tumors with 18F-FDG was the first oncologic application of PET Diagnostic limitations Relatively lower sensitivity of lesion detection Variability in 18F-FDG uptake Increase in inflammatory lesions

7 Radiation necrosis - usually seen between 2 to 32 months after radiation therapy MRI: ring enhancing region in the left parietal-temporal area on post-gadolinium enhanced images FDG PET exam- no tracer uptake consistent with postsurgical and post radiation change. MR spectroscopy can also be performed to evaluate for radiation necrosis versus tumor recurrence. The cholinecreatinine ratio and choline-nacetyl aspartate ratio are significantly higher in recurrent tumor and in radiation necrosis. A combined diagnostic threshold of a choline-creatine ratio greater than 1.11 and a choline-n-acetyl aspartate ratio greater than 1.17 has a sensitivity of 89% and a specificity of 83% for the identification of tumor. An elevated lipid-lactate peak and a generalized decrease in other metabolite levels suggests radiation necrosis

8 Biologic process and tracers Energy metabolism [18F]-2-fluoro-2-deoxyglucose (FDG) 1-[11C]glucose [15O]O2, [15O]H2O, [15O]CO Amino acid transport and incorporation L-[methyl-11C]methionine (MET) L-[11C]tyrosine L-[18F]fluorotyrosine L-[11C]leucine Neuroreceptor DNA synthesis F Dopa 2-[11C]thymidine [18F]3Vdeoxy-3V-fluorothymidine (FLT) [18F]- or [11C]-2V-fluoro-5-methyl-1-b-D-arabinofuranosyluracil Membrane/lipid biosynthesis Hypoxia Tumor Neovascularity 1-[1-11C]acetate [11C]choline [18F]fluorocholine [18F]fluoromisonidazole RGD Peptides

9 C11 Methionine PET 11CMET is considered to accumulate preferentially in tumor tissue, with a low level of accumulation in normal brain tissue, providing good contrast to highlight tumor uptake. The margins of tumors, as assessed by positron emission tomography (PET) with amino acid tracers like methyl-[ 11C]Lmethionine ([11C]MET), are frequently wider than those assessed by MRI or CT. This phenomenon is even more pronounced in low-grade tumors and in diffuse gliomatosis because of their frequent lack of contrast enhancement in MRI.

10 C]MET is a sensitive tracer in tumor detection, and it differentiates benign from malignant lesions with high sensitivity and specificity with relatively low background activity in normal brain tissue. 11 [11C]MET uptake correlates to cell proliferation in cell culture, Ki-67 expression, proliferating cell nuclear antigen expression and microvessel density, indicating its role as a marker for active tumor proliferation and angiogenesis. Patients with tumors that showed stable of reduced MET uptake after radiotherapy lived longer MET PET is sensitive in detecting changes in tumor volume over time in low grade gliomas.

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13 11C-MET PET can differentiate tumor recurrence from radiation necrosis. The L/N mean of 11CMET PET may be the most valuable index for this differential diagnosis for both metastatic brain tumors and gliomas.

14 Low grade oligodendroglioma FDG PET

15 Right frontal high grade glioma

16 High grade glioma FDG PET

17 FDG & C11 Met Glioma

18 High grade tumor MET & FDG PET

19 FDG & C11 Met PET in low grade Glioma FDG C11 MET

20 FDG & C11 Met PET in low grade Glioma

21 PETMRI Met PET in Insular Glioma MRI C11 Met PETMRI

22 Recurrent right frontal glioma FDG PET, C11 MET PET

23 Bicentric gliosarcoma MET PET

24 FDG & C11 MET glioma You can plan biopsy site Based on metabolic info

25 F18 DOPA Uptake reflects the activity of the decarboxylating enzyme and the storage capacity of dopamine. 18F-DOPA is an analog of L-DOPA, this positron emitting compound is clinically used to trace the dopaminergic pathway and to evaluate striatal dopaminergic presynaptic function Useful for monitoring disease progression

26 F FOPA PET SCAN The large neutral amino acid transport system is highly expressed not only in the nigrostriatal region as a physiologic feature of normal brain but also in brain tumors as a pathologic feature, causing an increased uptake of amino acids, compared with that in normal brain. Longer half-life compared to C11 methionine.

27 FDOPA PET FDOPA PET helps in differentiating recurrent or progressive brain metastases from late or delayed radiation injury. The mean time to progression was 4.6 times longer for lesions with negative 18F-FDOPA PET results than for lesions with positive 18FFDOPA PET results (76.5 vs mo; P, 0.001).18F-FDOPA PET findings tended to predict overall survival. Among the 83 lesions included in the study, 32 (39%) were classified as recurrences and 51 (61%) were determined to be radiation injury. FDOPAPET was able to differentiate between recurrence and radiation injury with a sensitivity of 81%, specificity of 84%, and accuracy of 83%. The results of the study "demonstrated that F-18 FDOPA PET could distinguish between Recurrent or Progressive BM and Late or Delayed Radiation Injury with a high diagnostic accuracy in a population of patients in whom RPBM was suggested by MR imaging," the authors concluded.

28 Results: Both high-grade and low-grade tumors were well visualized with 18F-FDOPA. The sensitivity for identifying tumors was substantially higher with 18F-FDOPA PET than with 18F-FDG PET at comparable specificities, as determined by simple visual inspection, especially for the assessment of low-grade tumors The high diagnostic accuracy of 18F-FDOPA PET at these thresholds was confirmed with the additional 51 patients (a total of 81 patients: sensitivity,98%; specificity, 86%; positive predictive value, 95%;negative predictive value, 95%). No significant difference in tumor uptake on 18F-FDOPA scans was seen between low-grade and high-grade tumors (P ) or between contrast-enhancing and non-enhancing tumors (P50.97). Radiation necrosis was generally distinguishable from tumors on 18F-FDOPA scans (P, ). Conclusion: 18F-FDOPA PET was more accurate than18f-fdg PET for imaging of lowgrade tumors and evaluating recurrent tumors. 18F-FDOPA PET may prove especially useful for imaging of recurrent low-grade tumors and for distinguishing tumor recurrence from radiation necrosis.

29 Conclusion: 18F-FDOPA uptake is significantly higher in high-grade than in low-grade tumors in newly diagnosed but not recurrent tumors that had been treated previously. A significant correlation between 18F-FDOPA uptake and tumor proliferation in newly diagnosed tumors was observed, whereas this correlation was not identified for recurrent tumors. Thus, 18F-FDOPA PET might serve as a noninvasive marker of tumor grading and might provide a useful surrogate of tumor proliferative activity in newly diagnosed gliomas. J Nucl Med 2010; 51:

30 Conclusion: 18F-DOPA PET/CT changed the intended management of 41% of patients with brain tumors, and intended management changes were implemented in 75% of these. These changes suggest a potentially important clinical role of imaging amino acid transport in the management of brain tumor patients. J Nucl Med 2012; 53:

31 If only this image is considered for radiotherapy planning then one will treat this region GEOGRAPHICAL MISS CAN BE AVOIDED For want of C11 MET One will miss this

32 FDOPA PET SCAN

33 Demonstration of tumor neovascularity

34 DOPA PSMA MRI FINDINGS- elsewhere Porencephalic cavity in the right frontal lobe involving the cortex and subcortical white matter with significant adjoining gliosis in the deep white matter of right frontal lobe. Altered signal intensity in the periventricular region of frontal horn of left lateral ventricle with enhancement. Focal nodular hyperintense lesion in the subcortical white matter of left frontal lobe with post contrast enhancement. Other MRI findings as described above. Findings are likely secondary to post therapy changes, suggested close follow up.

35 LOW GRADE GLIOMA BRAIN STEM CT MRI PSMAPET FDOPA PET Comments: Findings are consistent with brain stem glioma. F-DOPA uptake in the periphery of the cystic lesion in the brain stem suggestive of residual disease. PSMA uptake described above in the periphery of this lesion is due to PSMA expression in the vasculature surrounding the tumor.

36 Glioblastoma multiforme C11 Choline PET

37 C11 Choline PET Membrane synthesis. Why we stopped it? HCG

38 Intense accumulation in Necrosis.

39 (Dotanoc) Post therapy Response Meningioma Treated by Lu177 Dotatate (PET CT)

40 PETMRI

41 3 T Skyra 128 mct mmr

42 DAT -123I-FP-CIT,TRODAT Uptake reflects the activity of the transmembrane dopamine transporter. Dopamine transporter is downregulated in early disease, making 123I-FP-CIT SPECT more sensitive for the early detection of Parkinson s disease. For monitoring disease progression, the 2 compounds are theoretically equivalent.

43 FDOPA SCAN IN EVALUATION FOR PARKINSONISM Normal Control image FDOPA IMAGES OF PATIENT FDOPA uptake in brain showing uniform symmetrical uptake in the Caudate nucleus and Putamen. Reduced tracer uptake seen in the bilateral Putamen-left more reduced than right

44 Normal Control image FDOPA uptake in brain showing uniform symmetrical uptake in the Caudate nucleus and Putamen. MRI Images

45 Normal Control image FDOPA IMAGES FDOPA uptake in brain showing uniform symmetrical uptake in the Caudate nucleus and Putamen. Reduced tracer uptake seen in the bilateral Putamen. Right more reduced than left

46 Consider F-DOPA scan

47 Results: Fusion technology facilitated precise anatomical localization of 18FFDOPA activity. In group I, all 21 cases showed pathology-confirmed tumor. Of these, 18FFDOPA scans were positive in 9/10 (90%) previously unresected tumors, and 11/11 (100%) of recurrent tumors(the sensitivity of 18F-FDOPA was 95.2% and that of MRI was 90.5%). Of the 70 patients in group II, concordance between MRI and 18F-FDOPA was found in 49/54 (90.1%) of patients with sufficient follow-up; in the remaining 16 patients concordance could not be determined due to lack of follow-up. 18FFDOPA labeling was comparable in both high- and low-grade gliomas and identified both enhancing and non-enhancing tumor equally well. In some cases, 18F-FDOPA activity preceded tumor detection on MRI.

48 FDOPA PET may have utility in distinguishing non-enhancing tumor from other causes of T2W signal change such as gliosis, edema, etc Non-enhancing tumor regions on contrast-enhanced T1W MRI (A) show high 18F-FDOPA activity on the fused images (B, arrow) posterior to the resection cavity, without associated contrast enhancement. There is T2W signal abnormality anterior and posterior to the resection cavity (C, arrowheads), but only the region of T2W signal posterior to the resection cavity demonstrates abnormal 18F-FDOPA activity (D, arrow). This region was resected and confirmed to be recurrent tumor.

49 In this patient, elevated 18FFDOPA activity is seen at the margins of the resection cavity corresponding to a region of abnormal contrast enhancement (not shown). More superiorly, a non-enhancing area subtly expands the cortex in the parasagittal frontal lobe as shown on axial T2W MRI (A, arrow) also exhibits increased 18F-FDOPA activity (B, arrow). There was significant interval tumor growth into this previously PETdelineated tumor region on 7month followup MRI scan (T2W MRI (C, arrow) and contrasted-enhanced T1W MRI (D, FDOPA uptake delineated a region of tumor that was inconspicuous on MRI and which preceded abnormal contrast-enhancement on MRI

50 18F-FDOPA labeling differentiates post-surgical changes from recurrent tumor. Seven month follow-up MRI for a resected grade III oligodendroglioma exhibits contrast-enhanced areas (A, arrow) that might represent either postsurgical change or recurrent tumor; however 18F-FDOPA activity on PET-MRI fusion (B, arrow) suggests the possibility of tumor recurrence. A subsequent follow-up MRI 2 months (C, arrow) and 3 months (D, arrow) later shows increased enhancement into the area previously delineated by 18FFDOPAactivity the metabolic abnormality on 18FFDOPA PET preceded the local tumor recurrence on MRI, suggesting that 18F-FDOPA may detect residual tumor not clearly defined by MRI alone.

51 PETCT Radiotherapy plan How we do it FDOPA injected 15 min - One image acquired Finish diagnostic scan & call for RT - plan after 2 hours. If already done earlier then inject again on the day of the plan Casts, Radiotherapist,Physicist or Technician usually accompanies Flat couch like Radiotherapy couch is used. Moving lasers are used to mark fiducials on the cast used for immobilization

52 Steps in RT Planning Immobilization CT Simulation [PET CT] Image acquisition [DICOM] Image fusion [CT/MRI/PETCT] Anatomical+Functional Volume delineation [GTV,CTV,PTV,OAR] Planning [Optimal plan selection] Data transfer [Lantis] Set up and verification [EPID] Treatment delivery Monitoring Follow up

53 Immobilization

54 Simulation [CT,PET CT] Image acquisition C11 MET : 15 min Plan and therapy set up finished same time Extremely demanding. FDOPA : Image at 15 min and then RT plan at 1-2 hours later.

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57 Response evaluation for Chemoradiation HCG

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59 C11 Met PET Post Rx

60 Thank You HCG