Dataset Information

MRI and amino acid PET detection of whole-brain tumor burden.

ABSTRACT:

Background

[¹⁸F]fluciclovine amino acid PET has shown promise for detecting brain tumor regions undetected on conventional anatomic MRI scans. However, it remains unclear which of these modalities provides a better assessment of the whole brain tumor burden. This study quantifies the performance of [¹⁸F]fluciclovine PET and MRI for detecting the whole brain tumor burden.

Methods

Thirteen rats were orthotopically implanted with fluorescently transduced human glioblastoma cells. Rats underwent MRI (T1- and T2-weighted) and [¹⁸F]fluciclovine PET. Next brains were excised, optically cleared, and scanned ex vivo with fluorescence imaging. All images were co-registered using a novel landmark-based registration to enable a spatial comparison. The tumor burden identified on the fluorescent images was considered the ground truth for comparison with the in vivo imaging.

Results

Across all cases, the PET sensitivity for detecting tumor burden (median 0.67) was not significantly different than MRI (combined T1+T2-weighted) sensitivity (median 0.61; p=0.85). However, the combined PET+MRI sensitivity (median 0.86) was significantly higher than MRI alone (41% higher; p=0.004) or PET alone (28% higher; p=0.0002). The specificity of combined PET+MRI (median=0.91) was significantly lower compared with MRI alone (6% lower; p=0.004) or PET alone (2% lower; p=0.002).

Conclusion

In these glioblastoma xenografts, [¹⁸F]fluciclovine PET did not provide a significant increase in tumor burden detection relative to conventional anatomic MRI. However, a combined PET and MRI assessment did significantly improve detection sensitivity relative to either modality alone, suggesting potential value in a combined assessment for some tumors.

SUBMITTER: Chen P

PROVIDER: S-EPMC10558180 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

MRI and amino acid PET detection of whole-brain tumor burden.

Chen Peng P Scarpelli Matthew L ML Healey Debbie R DR Mehta Shwetal S Quarles C Chad CC

Frontiers in oncology 20230921

<h4>Background</h4>[<sup>18</sup>F]fluciclovine amino acid PET has shown promise for detecting brain tumor regions undetected on conventional anatomic MRI scans. However, it remains unclear which of these modalities provides a better assessment of the whole brain tumor burden. This study quantifies the performance of [<sup>18</sup>F]fluciclovine PET and MRI for detecting the whole brain tumor burden.<h4>Methods</h4>Thirteen rats were orthotopically implanted with fluorescently transduced human g ...[more]

PMID: 37810983

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Project description:IntroductionAmino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural (18)F-labeled amino acids, (R)- and (S)-[(18)F]FAMP 1 and (R)- and (S)-[(18)F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo for their potential utility in brain and systemic tumor imaging based upon primarily system A transport with positron emission tomography (PET).MethodsThe transport of enantiomers of [(18)F]FAMP 1 and [(18)F]MeFAMP 2 was measured through in vitro uptake assays in human derived cancer cells including A549 (lung), DU145 (prostate), SKOV3 (ovary), MDA MB468 (breast) and U87 (brain) in the presence and absence of amino acid transporter inhibitors. The in vivo biodistribution of these tracers was evaluated using tumor mice xenografts at 15, 30, 60 and 120 min post injection.ResultsAll four tracers showed moderate to high levels of uptake (1-9%ID/5×10(5) cells) by the cancer cell lines tested in vitro. AAT cell inhibition assays demonstrated that (R)-[(18)F]1 and (S)-[(18)F]1 entered these tumor cells via mixed AATs, likely but not limited to system A and system L. In contrast, (R)-[(18)F]2 and (S)-[(18)F]2 showed high selectivity for system A AAT. Similar to the results of in vitro cell studies, the tumor uptake of all four tracers was good to high and persisted over the 2 hours time course of in vivo studies. The accumulation of these tracers was higher in tumor than most normal tissues including blood, brain, muscle, bone, heart, and lung, and the tracers with the highest in vitro selectivity for system A AAT generally demonstrated the best tumor imaging properties. Higher uptake of these tracers was observed in the pancreas, kidney and spleen compared to tumors.ConclusionsThese preclinical studies demonstrate good imaging properties in a wide range of tumors for all four amino acids evaluated with (R)-[(18)F]2 having the highest selectivity for system A AAT.

Project description:Our aim was to introduce and validate qPSMA, a semiautomatic software package for whole-body tumor burden assessment in prostate cancer patients using 68Ga-prostate-specific membrane antigen (PSMA) 11 PET/CT. Methods: qPSMA reads hybrid PET/CT images in DICOM format. Its pipeline was written using Python and C++ languages. A bone mask based on CT and a normal-uptake mask including organs with physiologic 68Ga-PSMA11 uptake are automatically computed. An SUV threshold of 3 and a liver-based threshold are used to segment bone and soft-tissue lesions, respectively. Manual corrections can be applied using different tools. Multiple output parameters are computed, that is, PSMA ligand-positive tumor volume (PSMA-TV), PSMA ligand-positive total lesion (PSMA-TL), PSMA SUVmean, and PSMA SUVmax Twenty 68Ga-PSMA11 PET/CT data sets were used to validate and evaluate the performance characteristics of qPSMA. Four analyses were performed: validation of the semiautomatic algorithm for liver background activity determination, assessment of intra- and interobserver variability, validation of data from qPSMA by comparison with Syngo.via, and assessment of computational time and comparison of PSMA PET-derived parameters with serum prostate-specific antigen. Results: Automatic liver background calculation resulted in a mean relative difference of 0.74% (intraclass correlation coefficient [ICC], 0.996; 95%CI, 0.989;0.998) compared with METAVOL. Intra- and interobserver variability analyses showed high agreement (all ICCs > 0.990). Quantitative output parameters were compared for 68 lesions. Paired t testing showed no significant differences between the values obtained with the 2 software packages. The ICC estimates obtained for PSMA-TV, PSMA-TL, SUVmean, and SUVmax were 1.000 (95%CI, 1.000;1.000), 1.000 (95%CI, 1.000;1.000), 0.995 (95%CI, 0.992;0.997), and 0.999 (95%CI, 0.999;1.000), respectively. The first and second reads for intraobserver variability resulted in mean computational times of 13.63 min (range, 8.22-25.45 min) and 9.27 min (range, 8.10-12.15 min), respectively (P = 0.001). Highly significant correlations were found between serum prostate-specific antigen value and both PSMA-TV (r = 0.72, P < 0.001) and PSMA-TL (r = 0.66, P = 0.002). Conclusion: Semiautomatic analyses of whole-body tumor burden in 68Ga-PSMA11 PET/CT is feasible. qPSMA is a robust software package that can help physicians quantify tumor load in heavily metastasized prostate cancer patients.

Dataset Information

MRI and amino acid PET detection of whole-brain tumor burden.

Background

Methods

Results

Conclusion

Publications

MRI and amino acid PET detection of whole-brain tumor burden.

Similar Datasets

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