[¹¹C]Methionine and [¹¹C]PBR28 as PET Imaging Tracers to Differentiate Metastatic Tumor Recurrence or Radiation Necrosis

Abstract

Purpose: As stereotactic radiosurgery (SRS) and immunotherapy are increasingly used to treat brain metastases, incidence of radiation necrosis (RN) is consequently rising. Differentiating tumor regrowth (TR) from RN is vital in management but difficult to assess using MRI. We hypothesized that tumor methionine levels would be elevated given increased metabolism and high amino acid uptake, whereas RN would increase inflammation marked by upregulated translocator protein (PBR-TSPO), which can be quantified with specific PET tracers. Procedures: We performed a feasibility study to prospectively evaluate [11C]methionine and [11C]PBR28 using PET in 5 patients with 7 previously SRS-treated brain metastases demonstrating regrowth to differentiate TR from RN. Results: Sequential imaging with dual tracers was well-tolerated. [11C]methionine was accurate for detecting pathologically confirmed TR in 7/7 lesions, whereas [11C]PBR28 was only accurate in 3/7 lesions. Tumor PBR-TSPO expression was elevated in both melanoma and lung cancer cells, contributing to lack of specificity of [11C]PBR28-PET. Conclusion: Sequential use of PET tracers is safe and effective. [11C]Methionine was a reliable TR marker, but [11C]PBR28 was not a reliable marker of RN. Studies are needed to determine the causes of post-radiation inflammation and identify specific markers of RN to improve diagnostic imaging.

Have (R)-[11C]PK11195 challengers fulfilled the promise? A scoping review of clinical TSPO PET studies

“…These results highlighted the heterogeneity of the immune tumour microenvironment on one hand, and on the other hand, the fact that neuroinflammation may not overlap with tumour proliferation. As another example of this caveat, neuroinflammation in the context of brain metastases was recently reported in 5 cases of non-small cells lung carcinoma and melanoma brain metastases [ 191 ], but [ 11 C]PBR28, in contrast to [ 11 C]methionine, could not differentiate metastatic tumour recurrence from neuroinflammation-induced radiation necrosis.…”

Brain tumours, brain metastases, and neuroinflammation: Insights from neuroimaging studies.

“…Thus, the use of the [ 11 C]methionine and [ 11 C]PBR28 tracers in PET was evaluated in 5 patients previously treated brain metastases showing regrowth. The use of [ 11 C]methionine could accurately identify pathologically confirmed tumor regrowth in all 7 lesions examined, whereas [ 11 C]PBR28 could only identify 3 of 7 lesions, indicating that the former, but not the later tracer can be used as a reliable marker [84].…”

Molecular Imaging of Brain Metastases with PET

“…A head-to-head comparison study conducted by Tomura et al found that 11C-MET PET was better than FDG PET in distinguishing radiation necrosis from recurrent metastatic disease in the brain (38,40). Another recent study by Tran et al found that 11C-MET was a reliable marker for detecting recurrent disease in the post radiation setting; for example, 11C-MET was able to correctly identify pathologically confirmed recurrent disease in 7 lesions in 5 patients (41,42).…”