¹⁸F-FDG PET-CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by ¹⁸F-FDOPA PET-CT

A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available). The patient was then referred for ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. ¹⁸F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-¹⁸F-fluoro-L-phenylalanine (¹⁸F-FDOPA) PET-CT was done, 5 days after ¹⁸F-FDG PET-CT. The study revealed an ¹⁸F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months’ follow-up.

Fig. 1.

a, b ¹⁸F-FDG PET-CT. c, d ¹⁸F-FDOPA. e, f Six-month follow-up MRI

Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited [1]. ¹⁸F-FDG PET was the first tracer used for assessment of brain tumours [2]; however, it has a low tumour-to-background ratio in brain, limiting its utility. ¹⁸F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake than low-grade gliomas [3, 4]. Therefore, in spite of its limitations, ¹⁸F-FDG PET-CT is used for imaging of high-grade glioma. Amino acid PET radiotracers including ¹⁸F-FDOPA display superior contrast to ¹⁸F-FDG because of low uptake of amino acids in normal brain tissue [5]. They have particularly special value in the detection of low-grade gliomas [6]. However, ¹⁸F-FDOPA tumour uptake cannot provide reasonable predictions about tumour grade and proliferation in recurrent tumours that have undergone treatments [7]. Also, their difficult synthesis or need for an on-site cyclotron limits their widespread use. The present case shows the utility of ¹⁸F-FDOPA PET-CT in detection of a recurrent high-grade AA that was missed by ¹⁸F-FDG PET-CT. It highlights that ¹⁸F-FDG PET-CT can be falsely negative, even in high-grade recurrent gliomas and, therefore, in cases with strong clinical suspicion ¹⁸F-FDOPA PET-CT can be an alternative imaging modality to rule out recurrence even when ¹⁸F-FDG PET-CT is negative.