Joint Program in Nuclear Medicine

Combined F-18 FDG and C-11 Methionine PET for Cerebral Tumors

Tung Vu, MB BS
Alan J. Fischman, MD PhD

September 26, 2000

Presentation

Imaging Technique

• MRI was performed with gadolinium and spectroscopic analysis.
• F-18 FDG PET images were acquired 45 minutes after intravenous administration of 5.3 mCi of FDG.
• C-11 methionine PET images were acquired after intravenous administration of 27.0 mCi of C-11 methionine.

Imaging Findings

• Initial MRI scan demonstrated irregularly enhancing lesions in the splenium of the corpus callosum (show by arrow), left cingulate gyrus and adjacent to the left anterior frontal horn (shown by arrowhead). Spectroscopic evaluation was suggestive of tumor and most likely diagnosis was thought to be glioblastoma multiforme.
• F-18 FDG PET revealed moderately increased tracer accumulation in the right parietal white matter (shown by arrow) consistent with metabolically viable tumor, but no abnormal uptake elsewhere.
• The C-11-Methionine PET study showed increased uptake in the right parietal region, crossing the midline in the callosal region (shown by arrows), as well as in the anterior left frontal region (shown by arrowhead). Fusion images of the methionine and FDG show the correspondence of the location between the studies.

Differential Diagnosis

Diagnosis

Discussion

General

• Primary CNS tumors
  • 1-2% of all malignancies (incidence 10.9 per 100,000 in 1995)
  • 55% are malignant (of these 50% are gliomas, 15% meningiomas; other types are much less common)
• Appropriate follow-up after treatment requires accurate differentiation of:
  • Post-surgical changes
  • Radiation-induced necrosis
  • Recurrent tumor

Anatomical imaging with CT/MRI

• Contrast enhancement at surgical site is non-specific
  • Common in initial days/weeks after surgery and may persist for several months
  • Radiation necrosis may enhance (usually appears after several months)
• Spectroscopic analysis may be of assistance (choline:

Positron emission tomography (PET)

• Functional/metabolic imaging with nuclear medicine tracers may be useful for:
  • Grading of tumor
  • Prognostic stratification
  • Assessment of tumor recurrence
• Most frequently used PET radiotracers:
  • F-18 fluoro-deoxyglucose (FDG)
  • C-11 methionine
  • Other less common C-11 amino acid tracers: C-11 thymidine, C-11 tyrosine, C-11 leucine

Fluoro-deoxyglucose (FDG)

General

• Initial PET agent used in assessment of cerebral neoplasms
• Glucose analog labeled with fluorine-18 (see below)
• Same cellular uptake as glucose, but is not dephosphorylated so is not further metabolized
• High uptake in:
  • Viable tumor cells
  • Tumor-associated macrophages
• Quantification possible using
  • Standardized uptake ratio (SUV)
  • Cerebral metabolic rate for glucose (CMR-Glu)
• Qualitative comparison of tumor uptake to contralateral normal brain parenchyma also useful

Fluorine-18

• Cyclotron produced positron emitter produced by proton bombardment of O-18 water
• Reaction: O-18 (p,n) F-18, yielding fluoride ion
• 511 keV photons (high energy)
• Half life 109.7 minutes

Advantages

• Clinical assessment
  • Patient stratification (see grade, prognosis below)
  • Detection of early tumor recurrence following surgery, radiotherapy and chemotherapy
  • Differentiation of recurrence and radiation necrosis
    • Superior to contrast CT in identifying early recurrence
    • Hypermetabolic lesions in areas of prior resection had early tumor recurrence
    • Hypometabolic abnormalities revealed radiation necrosis
• Assessment of grade
  • More accurate than contrast CT for tumor grading (early NIH work)
  • Higher glucose metabolism in poorly differentiated (higher grade) tumors
  • Increase in previous low-grade indicates malignant degeneration
  • Uptake may persist in anaplastic areas with necrosis
• Assessment of prognosis
  • Better predictor of outcome than surgical biopsy
    • CMR-Glu >1.4, median survival 5 months; <1.4, median survival 19 months
  • In recurrence associated with high grade tumors:
    • Hypometabolic lesions indicated a 1-year survival of 78%
    • Hypermetabolic lesions had a 1-year survival of only 29%

Disadvantages

• Relatively low tumor:background ratio in brain
  • High background due to high glucose utilization in normal gray matter
  • Small amounts of tumor tissue may be concealed
• Not useful for evaluating extent of tumor
• Non-specific: intense focal inflammation can lead to a false positive scan

Amino acid analogs (e.g. C-11 methionine)

General

• C-11 methionine is most commonly used agent
• Exact mechanism of uptake not known; factors influencing uptake probably include:
  • Membrane amino acid transport
  • Integrity of blood brain barrier
  • Protein synthesis (N.B. Blockage of protein synthesis does not seem to influence uptake)
• Using microautoradiogaphy in animal non-CNS models, uptake has been shown to be:
  • Low in macrophages and non-neoplastic cells (unlike FDG)
  • Proportional to amount of viable cells
• Quantification also possible, as with FDG (e.g. differential absorption ration, DAR)

Carbon-11

• Produced by proton bombardment of N-14 nitrogen gas
• Reaction: N-14 (p,a) C-11, yielding carbon dioxide gas
• Short half-life of 20.3 minutes; therefore requires an on-site cyclotron
• Used because fluorine-18 labeled amino acid analogs have low radiochemical purity

Advantages of C-11 methionine over FDG in imaging of cerebral neoplasms

• Markedly lower background activity in normal gray and white matter
• Easier lesion detection, especially small tumors (primary or recurrent)
• Generally uptake increases more (than FDG) with increasing tumor grade; highly useful for:
  • Detecting astrocytomas
  • Evaluating extent of astrocytomas
  • Differentiating benign from malignant astrocytomas (very high uptake in glioblastoma)

Disadvantages of C-11 methionine

• Requirement for on-site cyclotron due to short half-life of C-11
• Microscopic necrosis decreases uptake, more than appears to be the case with FDG
• No definite correlation demonstrated between uptake/protein synthesis rate and tumor grade
• Limited in evaluation of histological grade
• Less specific
  • Increased accumulation less related to proliferative potential, when compared to FDG
  • Does not distinguish well between low grade astrocytomas
  • Increased in abscess
  • Increased uptake reported around acute hematoma, cerebral abscess (more than FDG)

Conclusions

• Both F-18 FDG and C-11 methionine are useful for initial/follow-up assessment of astrocytomas
• Combination of both agents is complementary
• C-11 methionine may be the better single agent
• Use of C-11 methionine is currently limited by the requirement for an on-site cyclotron

References

1. Cook GJ, Maisey MN, Fogelman I. Normal variants, artefacts and interpretative pitfalls in PET imaging with 18-fluoro-2-deoxyglucose and carbon-11 methionine. European Journal of Nuclear Medicine. 26(10):1363-1378, 1999 Oct.
2. Derlon JM, Petit-Taboue MC, Chapon F, Beaudouin V, Noel MH, Creveuil C, Courtheoux P, Houtteville JP. The in vivo metabolic pattern of low-grade brain gliomas: a positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine. Neurosurgery. 40(2):276-287, 1997 Feb.
3. Goldman S, Levivier M, Pirotte B, Brucher JM, Wikler D, Damhaut P, Dethy S, Brotchi J, Hildebrand J. Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy. Journal of Nuclear Medicine. 38(9):1459-1462, 1997 Sep.
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6. Ogawa T, Inugami A, Hatazawa J, Kanno I, Murakami M, Yasui N, Mineura K, Uemura K. Clinical positron emission tomography for brain tumors: comparison of fludeoxyglucose F-18 and L-methyl-11C-methionine. AJNR: American Journal of Neuroradiology. 17(2):345-353, 1996 Feb.
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