BACKGROUND: To evaluate and compare the diagnostic power of [18F]FLT-PET with ceMRI in patients with brain tumours or other focal lesions. METHODS: 121 patients with suspected brain tumour or those after brain tumour surgery were enroled in this retrospective study (61 females, 60 males, mean age 37.3 years, range 1-80 years). All patients underwent [18F]FLT-PET/MRI with gadolinium contrast agent application. In 118 of these patients, a final diagnosis was made, verified by histopathology or by follow-up. Agreement between ceMRI and [18F]FLT-PET of the whole study group was established. Further, sensitivity and specificity of ceMRI and [18F]FLT-PET were calculated for differentiation of high-grade vs. low-grade tumours, high-grade vs. low-grade tumours together with non-tumour lesions and for differentiation of high-grade tumours from all other verified lesions. RESULTS: [18F]FLT-PET and ceMRI findings were concordant in 119 cases (98%). On closer analysis of a subset of 64 patients with verified gliomas, the sensitivity and specificity of both PET and ceMRI were identical (90% and 84%, respectively) for differentiating low-grade from high-grade tumours, if the contrast enhancement and [18F]FLT uptake were considered as hallmarks of high-grade tumour. For differentiation of high-grade tumours from low-grade tumours and lesions of nontumorous aetiology (e.g., inflammatory lesions or post-therapeutic changes) in a subgroup of 93 patients by visual evaluation, the sensitivity of both PET and ceMRI was 90%, whereas the specificity of PET was slightly higher (61%) compared to ceMRI (57%). By receiver operating characteristic analysis, the sensitivity and specificity were 82% and 74%, respectively, when the threshold of SUVmax in the tumour was set to 0.9 g/ml. CONCLUSION: We demonstrated a generally very high correlation of [18F]FLT accumulation with contrast enhancement visible on ceMRI and a comparable diagnostic yield in both modalities for differentiating high-grade tumours from low-grade tumours and lesions of other aetiology.

Clinic of Neurosurgery Medical Faculty Masaryk University Brno 625 00 Czechia

Clinic of Neurosurgery University Hospital Brno Brno 625 00 Czechia

Department of Biophysics Medical Faculty Masaryk University Brno 625 00 Czechia

Department of Radiology and Nuclear Medicine Medical Faculty Masaryk University Brno 625 00 Czechia

Department of Radiology and Nuclear Medicine University Hospital Brno Jihlavská 20 Brno 625 00 Czech Republic

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Kim YZ, Kim CY, Lim DH. The overview of practical guidelines for gliomas by KSNO, NCCN, and EANO. Brain Tumor Res Treat. 2022;10(2):83. 10.14791/btrt.2022.0001. 10.14791/btrt.2022.0001 PubMed DOI PMC

Galldiks N, Lohmann P, Albert NL, Tonn JC, Langen KJ. Current status of PET imaging in neuro-oncology. Neuro-Oncology Adv. 2019;1(1):vdz010. 10.1093/noajnl/vdz010.10.1093/noajnl/vdz010 PubMed DOI PMC

Choi SJ, Kim JS, Kim JH, et al. [18F]3′-deoxy-3′-fluorothymidine PET for the diagnosis and grading of brain tumors. Eur J Nucl Med Mol Imaging. 2005;32(6):653–9. 10.1007/s00259-004-1742-3. 10.1007/s00259-004-1742-3 PubMed DOI

Shaw TB, Jeffree RL, Thomas P, et al. Diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography in the evaluation of glioma. J Med Imaging Radiat Oncol. 2019;63(5):650–6. 10.1111/1754-9485.12929. 10.1111/1754-9485.12929 PubMed DOI

Chen W, Delaloye S, Silverman DHS, et al. Predicting Treatment response of malignant gliomas to Bevacizumab and Irinotecan by Imaging Proliferation with [ 18 F] Fluorothymidine Positron Emission Tomography: a pilot study. JCO. 2007;25(30):4714–21. 10.1200/JCO.2006.10.5825.10.1200/JCO.2006.10.5825 PubMed DOI

Jacobs AH, Thomas A, Kracht LW, et al. 18F-Fluoro-l-Thymidine and 11 C-Methylmethionine as Markers of Increased Transport and proliferation in brain tumors. J Nucl Med. 2005;46(12):1948–58. PubMed

Shields AF, Grierson JR, Dohmen BM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med. 1998;4(11):1334–6. 10.1038/3337. 10.1038/3337 PubMed DOI

Toyohara J, Waki A, Takamatsu S, Yonekura Y, Magata Y, Fujibayashi Y. Basis of FLT as a cell proliferation marker: comparative uptake studies with [3H]thymidine and [3H]arabinothymidine, and cell-analysis in 22 asynchronously growing tumor cell lines. Nucl Med Biol. 2002;29(3):281–7. 10.1016/S0969-8051(02)00286-X. 10.1016/S0969-8051(02)00286-X PubMed DOI

Nikaki A, Papadopoulos V, Valotassiou V, et al. Evaluation of the performance of 18F-Fluorothymidine Positron Emission Tomography/Computed tomography (18F-FLT-PET/CT) in metastatic brain lesions. Diagnostics. 2019;9(1):17. 10.3390/diagnostics9010017. 10.3390/diagnostics9010017 PubMed DOI PMC

Ferdová E, Ferda J, Baxa J, et al. Assessment of grading in newly-diagnosed glioma using 18F-fluorothymidine PET/CT. Anticancer Res. 2015;35(2):955–9. PubMed

Ullrich R, Backes H, Li H, et al. Glioma Proliferation as assessed by 3‘-Fluoro-3’-Deoxy- l -Thymidine Positron Emission Tomography in patients with newly diagnosed high-Grade Glioma. Clin Cancer Res. 2008;14(7):2049–55. 10.1158/1078-0432.CCR-07-1553. 10.1158/1078-0432.CCR-07-1553 PubMed DOI

Shinomiya A, Kawai N, Okada M, et al. Evaluation of 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas. Eur J Nucl Med Mol Imaging. 2013;40(2):175–85. 10.1007/s00259-012-2275-9. 10.1007/s00259-012-2275-9 PubMed DOI

Morikawa A, Grkovski M, Patil S, et al. A phase I trial of sorafenib with whole brain radiotherapy (WBRT) in breast cancer patients with brain metastases and a correlative study of FLT-PET brain imaging. Breast Cancer Res Treat. 2021;188(2):415–25. 10.1007/s10549-021-06209-4. 10.1007/s10549-021-06209-4 PubMed DOI PMC

Wardak M, Schiepers C, Cloughesy TF, Dahlbom M, Phelps ME, Huang SC. 18F-FLT and 18F-FDOPA PET kinetics in recurrent brain tumors. Eur J Nucl Med Mol Imaging. 2014;41(6):1199–209. 10.1007/s00259-013-2678-2. 10.1007/s00259-013-2678-2 PubMed DOI PMC

Brahm CG, Den Hollander MW, Enting RH, et al. Serial FLT PET imaging to discriminate between true progression and pseudoprogression in patients with newly diagnosed glioblastoma: a long-term follow-up study. Eur J Nucl Med Mol Imaging. 2018;45(13):2404–12. 10.1007/s00259-018-4090-4. 10.1007/s00259-018-4090-4 PubMed DOI PMC

Boellaard R, O’Doherty MJ, Weber WA, et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37(1):181–200. 10.1007/s00259-009-1297-4. 10.1007/s00259-009-1297-4 PubMed DOI PMC

Thust SC, Van Den Bent MJ, Smits M. Pseudoprogression of brain tumors. Magn Reson Imaging. 2018;48(3):571–89. 10.1002/jmri.26171.10.1002/jmri.26171 PubMed DOI PMC

Yamamoto Y, Wong TZ, Turkington TG, Hawk TC, Reardon DA, Coleman RE. 3′-Deoxy-3′-[F-18]Fluorothymidine Positron Emission Tomography in patients with recurrent Glioblastoma Multiforme: comparison with Gd-DTPA enhanced magnetic resonance imaging. Mol Imaging Biol. 2006;8(6):340–7. 10.1007/s11307-006-0063-2. 10.1007/s11307-006-0063-2 PubMed DOI

Nowosielski M, DiFranco MD, Putzer D et al. A Annala ed. 2014 An intra-individual comparison of MRI, [18F]-FET and [18F]-FLT PET in patients with high-Grade Gliomas. PLoS ONE 9 4 e95830 10.1371/journal.pone.0095830. 10.1371/journal.pone.0095830 PubMed DOI PMC

Jeong SY, Lee TH, Rhee CH, et al. 3′-Deoxy-3′-[18F]fluorothymidine and O-(2-[18F]fluoroethyl)-L-tyrosine PET in patients with suspicious recurrence of Glioma after Multimodal Treatment: initial results of a retrospective comparative study. Nucl Med Mol Imaging. 2010;44(1):45–54. 10.1007/s13139-009-0007-2. 10.1007/s13139-009-0007-2 PubMed DOI PMC

Cui M, Zorrilla-Veloz RI, Hu J, Guan B, Ma X. Diagnostic accuracy of PET for differentiating true glioma progression from Post Treatment-related changes: a systematic review and Meta-analysis. Front Neurol. 2021;12:671867. 10.3389/fneur.2021.671867. 10.3389/fneur.2021.671867 PubMed DOI PMC

Shishido H, Kawai N, Miyake K, Yamamoto Y, Nishiyama Y, Tamiya T. Diagnostic value of 11 C-Methionine (MET) and 18F-Fluorothymidine (FLT) Positron Emission Tomography in Recurrent High-Grade gliomas; differentiation from Treatment-Induced tissue necrosis. Cancers. 2012;4(1):244–56. 10.3390/cancers4010244. 10.3390/cancers4010244 PubMed DOI PMC

Nihashi T, Dahabreh IJ, Terasawa T. Diagnostic accuracy of PET for recurrent glioma diagnosis: a Meta-analysis. AJNR Am J Neuroradiol. 2013;34(5):944–50. 10.3174/ajnr.A3324. 10.3174/ajnr.A3324 PubMed DOI PMC

de Zwart PL, van Dijken BRJ, Holtman GA, et al. Diagnostic Accuracy of PET Tracers for the differentiation of Tumor Progression from Treatment-related changes in high-Grade Glioma: a systematic review and metaanalysis. J Nucl Med. 2020;61(4):498–504. 10.2967/jnumed.119.233809. 10.2967/jnumed.119.233809 PubMed DOI

Yao Y, Tan X, Yin W, et al. Performance of 18 F-FAPI PET/CT in assessing glioblastoma before radiotherapy: a pilot study. BMC Med Imaging. 2022;22(1):226. 10.1186/s12880-022-00952-w. 10.1186/s12880-022-00952-w PubMed DOI PMC

Dimitrakopoulou-Strauss A, Pan L, Sachpekidis C. Kinetic modeling and parametric imaging with dynamic PET for oncological applications: general considerations, current clinical applications, and future perspectives. Eur J Nucl Med Mol Imaging. 2021;48(1):21–39. 10.1007/s00259-020-04843-6. 10.1007/s00259-020-04843-6 PubMed DOI PMC

Scarpelli M, Simoncic U, Perlman S, Liu G, Jeraj R. Dynamic 18 F-FLT PET imaging of spatiotemporal changes in tumor cell proliferation and vasculature reveals the mechanistic actions of anti-angiogenic therapy. Phys Med Biol. 2018;63(15):155008. 10.1088/1361-6560/aad1be. 10.1088/1361-6560/aad1be PubMed DOI

Wardak M, Schiepers C, Dahlbom M, et al. Discriminant analysis of 18F-Fluorothymidine kinetic parameters to Predict Survival in patients with recurrent high-Grade Glioma. Clin Cancer Res. 2011;17(20):6553–62. 10.1158/1078-0432.CCR-10-3290. 10.1158/1078-0432.CCR-10-3290 PubMed DOI PMC