fluciclovine-f-18 and Glioma

This pilot study aimed to evaluate the amino acid tracer F-FACBC with simultaneous PET/MRI in diagnostic assessment and neurosurgery of gliomas.. Eleven patients with suspected primary or recurrent low- or high-grade glioma received an F-FACBC PET/MRI examination before surgery. PET and MRI were used for diagnostic assessment, and for guiding tumor resection and histopathological tissue sampling. PET uptake, tumor-to-background ratios (TBRs), time-activity curves, as well as PET and MRI tumor volumes were evaluated. The sensitivities of lesion detection and to detect glioma tissue were calculated for PET, MRI, and combined PET/MRI with histopathology (biopsies for final diagnosis and additional image-localized biopsies) as reference.. Overall sensitivity for lesion detection was 54.5% (95% confidence interval [CI], 23.4-83.3) for PET, 45.5% (95% CI, 16.7-76.6) for contrast-enhanced MRI (MRICE), and 100% (95% CI, 71.5-100.0) for combined PET/MRI, with a significant difference between MRICE and combined PET/MRI (P = 0.031). TBRs increased with tumor grade (P = 0.004) and were stable from 10 minutes post injection. PET tumor volumes enclosed most of the MRICE volumes (>98%) and were generally larger (1.5-2.8 times) than the MRICE volumes. Based on image-localized biopsies, combined PET/MRI demonstrated higher concurrence with malignant findings at histopathology (89.5%) than MRICE (26.3%).. Low- versus high-grade glioma differentiation may be possible with F-FACBC using TBR. F-FACBC PET/MRI outperformed MRICE in lesion detection and in detection of glioma tissue. More research is required to evaluate F-FACBC properties, especially in grade II and III tumors, and for different subtypes of gliomas.

Topics: Adult; Aged; Brain Neoplasms; Carboxylic Acids; Cyclobutanes; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals

To retrospectively investigate the uptake of F-fluciclovine on PET/CT in patients with suspected recurrent high-grade glioma (HGG).. Twenty-one patients were included. The standard of truth was histopathologic interpretation if available. When histopathology was not available or rebiopsy did not show signs of malignancy, clinical follow-up including MRI and clinical outcome was considered the standard of truth.. All 21 patients met the reference standard of either histopathologic proof of HGG recurrence (n = 10) or disease progression clinically and with tumor growth corresponding to the primary tumor sites on follow-up MRI (n = 11). Median time from PET/CT to death was 5 months (range, 1-20 months). Median time from primary diagnosis to death was 14.5 months (range, 6 to >400). Average SUVmax of the lesions was 8.3 ± 5.3 (SD) and 0.34 ± 0.13 for normal brain tissue. Median lesion-to-background ratio was 21.6 (range, 3.1-84.4). In 4 patients, F-fluciclovine PET/CT detected small satellite tumors that had not been reported on MR.. The uptake of F-fluciclovine in clinically and/or histopathologically confirmed recurrent HGG is high compared with the uptake reported for other amino acid PET tracers. Because of the high tumor uptake and thus high tracer contrast, small satellite tumors with a diameter below usual reported PET spatial resolution and not reported on MRI were detected in 4 patients. As no patients with confirmed treatment-related changes were included, we cannot as of yet ascertain the ability of F-fluciclovine PET to discriminate between recurrent HGG and treatment-related changes, for example, pseudoprogression and radionecrosis.

Topics: Adult; Aged; Carboxylic Acids; Cyclobutanes; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Neoplasm, Residual; Positron Emission Tomography Computed Tomography; Recurrence; Retrospective Studies

Magnetic resonance imaging (MRI) can have a problem to delineate diffuse gliomas with an intact blood-brain barrier (BBB) especially when a marked peritumoral edema is present. We evaluated the potential of trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) positron emission tomography (PET) to delineate the extent of diffuse gliomas by comparing PET findings with autoradiography, in vivo and ex vivo MRI, and histopathology findings.. Dynamic PET was performed in rats with N-ethyl-N-nitrosourea-induced glioma for 60 min after anti-(18)F-FACBC injection. Contrast-enhanced MRI was performed before or after PET. The PET images were fused with in vivo and ex vivo MR images, and histopathological images for direct comparisons. Autoradiograms were compared with the results of Evans Blue (EB) extravasation (to assess BBB integrity) and hematoxylin-eosin staining.. Histopathological examination, including EB extravasation assessment, and enhanced T1-weighted MRI identified several diffuse gliomas with slight BBB disruption, similar to low-grade human gliomas. Anti-(18)F-FACBC uptake was specific and high in the gliomas, irrespective of BBB integrity. Higher anti-(18)F-FACBC uptake corresponded to areas of T2 hyperintensity, independent of gadolinium enhancement. Ex vivo autoradiography also showed high anti-(18)F-FACBC accumulation in tumors lacking EB extravasation and a correlation between anti-(18)F-FACBC accumulation and tumor cell density, but not EB extravasation.. Anti-(18)F-FACBC-PET allowed visualization of gliomas irrespective of BBB integrity. The tumor-to-normal uptake ratio of anti-(18)F-FACBC generally correlated with the relative cell density. Anti-(18)F-FACBC PET combined with MRI shows promise for preoperative glioma delineation.. Radiopharmaceuticals that cross the BBB, such as anti-(18)F-FACBC, are taken up by low-grade gliomas with equivocal MRI findings due to an intact BBB.. Surgery is the first-line therapy for low-grade gliomas; therefore, delineation of their extent in the presence of an intact BBB is essential to planning surgery that removes the entire neoplasm, which will positively affect long-term survival.

Topics: Alkylating Agents; Animals; Autoradiography; Blood-Brain Barrier; Brain Neoplasms; Carboxylic Acids; Cyclobutanes; Ethylnitrosourea; Female; Fluorine Radioisotopes; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Neoplasm Grading; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Inbred F344; Tissue Distribution

Amino acid PET tracers are promising for visualizing gliomas and evaluating radiochemotherapeutic effects. We compared the glioma detection and early response assessment utility between trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) by simultaneously analyzing their uptake by rat gliomas treated with and without temozolomide (TMZ) in vitro and in vivo.. C6 rat gliomas were incubated with low-dose TMZ to induce chemoresistance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated a significantly greater surviving fraction in the TMZ-resistant subline (C6R) than in drug-naive cells (C6). The anti-(14)C-FACBC and (3)H-Met uptakes were quantified using a triple-label accumulation assay to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation rate) in tumor cells. C6 and C6R cells were inoculated into the right and left basal ganglia, respectively, of rats. Efficacy of TMZ against the orthotopic gliomas was analyzed by MRI, Evans blue extravasation, anti-(14)C-FACBC and (3)H-Met autoradiography, and MIB-5 proliferation index.. The (3)H-TdR accumulation rate and amino acid tracer (anti-(14)C-FACBC and (3)H-Met) uptake significantly decreased 48 and 72 h, respectively, after TMZ treatment in C6 but not C6R cells. Anti-(14)C-FACBC uptake correlated significantly with (3)H-Met uptake and the (3)H-TdR accumulation rate. In the intracerebral glioma model, anti-(14)C-FACBC and (3)H-Met autoradiography clearly delineated the tumor extent, which spread well beyond the high-T2-intensity and enhancing lesions visible on MRI and Evans blue extravasation. TMZ significantly decreased anti-(14)C-FACBC and (3)H-Met uptake and the MIB-5 index of C6 but not C6R tumors. TMZ inhibited tracer uptake and tumor proliferation before morphological changes on MRI.. Anti-(14)C-FACBC, like (3)H-Met, was more sensitive than post-contrast T1-weighted MRI for detecting tumor extent and early tumor response to TMZ treatment. Anti-(18)F-FACBC should be a sensitive and precise imaging biomarker for tumor extent visualization and response assessment in glioma patients.

Topics: Animals; Blood-Brain Barrier; Brain Neoplasms; Carboxylic Acids; Cell Line, Tumor; Cell Proliferation; Cyclobutanes; Dacarbazine; Feasibility Studies; Glioma; Magnetic Resonance Imaging; Male; Methionine; Permeability; Rats; Temozolomide; Treatment Outcome

Positron emission tomography (PET) with amino acid tracers is useful for the visualization and assessment of therapeutic effects on gliomas. Our purpose is to elucidate the transport mechanisms of trans-1-amino-3-[¹⁸F]fluorocyclobutanecarboxylic acid (anti-[¹⁸F]FACBC) and L-[methyl-¹¹C]methionine ([¹¹C]Met) in normal human astrocytes (NHA), low-grade (Hs683, SW1088), and high-grade (U87MG, T98G) human glioma cell lines. Because the short half-lives of fluorine-18 and carbon-11 are inconvenient for in vitro experiments, trans-1-amino-3-fluoro[1-¹⁴C]cyclobutanecarboxylic acid (anti-[¹⁴C]FACBC) and L-[methyl-¹⁴C]methionine ([¹⁴C]Met) were used instead of the PET tracers. Time-course uptake experiments showed that uptake of anti-[¹⁴C]FACBC was 1.4-2.6 times higher than that of [¹⁴C]Met in NHA and low-grade glioma cells, and was almost equal to that of [¹⁴C]Met in high-grade glioma cells. To identify the amino acid transporters (AATs) involved in the transport of anti-[¹⁴C]FACBC and [¹⁴C]Met, we carried out competitive inhibition experiments using synthetic/naturally-occurring amino acids as inhibitors. We found that anti-[¹⁴C]FACBC uptake in the presence of Na⁺ was strongly inhibited by L-glutamine and L-serine (the substrates for ASC system AATs), whereas L-phenylalanine and 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (BCH, the substrates for L system AATs) robustly inhibited Na⁺-independent anti-[¹⁴C]FACBC uptake. Regardless of Na⁺, [¹⁴C]Met uptake was inhibited strongly by L-phenylalanine and BCH. Moreover, the exchange transport activity of L-glutamine for anti-[¹⁴C]FACBC was stronger than that of BCH in the presence of Na⁺, whereas that for [¹⁴C]Met was almost equal to BCH. These results demonstrate that ASC and L are important transport systems for anti-[¹⁸F]FACBC uptake, while system L is predominantly involved in [¹¹C]Met transport in human astrocytes and glioma cells.

Topics: Biological Transport; Carbon Radioisotopes; Carboxylic Acids; Cell Line, Tumor; Cyclobutanes; Glioma; Humans; Methionine