Tryptophan PET predicts spatial and temporal patterns of post-treatment glioblastoma progression detected by contrast-enhanced MRI

Abstract

Background Amino acid PET is increasingly utilized for the detection of recurrent gliomas. Increased amino acid uptake is often observed outside the contrast-enhancing brain tumor mass. In this study, we evaluated if non-enhancing PET+ regions could predict spatial and temporal patterns of subsequent MRI progression in previously treated glioblastomas. Methods Twelve patients with a contrast-enhancing area suspicious for glioblastoma recurrence on MRI underwent PET scanning with the amino acid radiotracer alpha-[11C]-methyl-L-tryptophan (AMT). Brain regions showing increased AMT uptake in and outside the contrast-enhancing volume were objectively delineated to include high uptake consistent with glioma (as defined by previous studies). Volume and tracer uptake of such non-enhancing PET+ regions were compared to spatial patterns and timing of subsequent progression of the contrast-enhancing lesion, as defined by serial surveillance MRI. Results Non-enhancing PET+ volumes varied widely across patients and extended up to 24 mm from the edge of MRI contrast enhancement. In 10 patients with clear progression of the contrast-enhancing lesion, the non-enhancing PET+ volumes predicted the location of new enhancement, which extended beyond the PET+ brain tissue in 6. In two patients, with no PET+ area beyond the initial contrast enhancement, MRI remained stable. There was a negative correlation between AMT uptake in non-enhancing brain and time to subsequent progression (r=−0.77, p=0.003). Conclusions Amino acid PET imaging could complement MRI not only for detecting glioma recurrence but also predicting the location and timing of subsequent tumor progression. This could support decisions for surgical intervention or other targeted therapies for recurrent gliomas.

Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts

“…Nevertheless, the high 18 F-FETrp uptake in the bladder and pancreas suggests that this tracer would not allow visualization of tumors in these organs because of high background activity. Despite the differences in distribution, both tracers demonstrated similarly low and continuous brain accumulation, suggesting that 18 F-FETrp will be suitable for the imaging of intracranial brain tumors as previously established with 11 C-AMT (18)(19)(20)(21)(22)(23)(24)(25)(26).…”

“…The total injected activity in mice for the 18 F-FETrp tracer was between 5.5 and 9.2 MBq (150-250 mCi), a dose commonly used in smallanimal PET studies of mice using 18 F-labeled PET tracers (39,40). Because of the shorter half-life of the 11 C isotope (20 min), a higher activity was administered in the AMT study (20)(21)(22) MBq equivalent to 550-600 mCi). This dose was previously determined by our group as sufficient to obtain high-quality images in the PDX tumor models (35).…”

“…11 C-AMT PET was originally designed to estimate brain serotonin synthesis in the context of neuropsychiatric disorders (15,16) but also demonstrated the ability to identify epileptic foci, epileptogenic tumors, and malformations (17,18). 11 C-AMT PET studies were further extended to nonepileptogenic primary and metastatic brain tumors (19)(20)(21)(22). These studies demonstrated variably high 11 C-AMT uptake in gliomas (18,23,24) and meningiomas (21) and showed strong prognostic value for survival in patients with recurrent glioblastoma (20).…”

Imaging tryptophan uptake with positron emission tomography in glioblastoma patients treated with indoximod

“…Tumoral SUVs were normalized by dividing their values by SUV measured in normal contralateral cortex, thus creating a tumor/cortex SUV ratio. Based on our previous studies, SUV tumor/cortex ratios 1.65 and above are consistent with recurrent GBM (rGBM) [28,34]. …”

Prognostic Molecular and Imaging Biomarkers in Primary Glioblastoma

“…20 The procedure for AMT-PET scanning has been described previously. 15,16,18,21 In brief, after 6 h of fasting, AMT (1 mCi/kg=37 MBq/kg) was injected intravenously. For collection of timed blood samples, a second venous line was established.…”