ORIGINAL RESEARCH article
Front. Neuroimaging
Sec. Clinical Neuroimaging
This article is part of the Research TopicAdvances in PET-CT Imaging - Vol. IIView all articles
Neuroimaging Evaluation of High Dose Methotrexate-Induced Neurotoxicity in Pediatric and Young Adults: A PET/MRI Study
Provisionally accepted
Zahra Shokri Varniab1
Hyun Gi Kim1,2Ricarda Von Krüchten1Yashas Ullas Lokesha1Kristina Elizabeth Hawk1Shashi Bhushan Singh1Tie Liang1Sarah Lu-Liang1
Lucia Baratto1
Michael Iv1
Heike Elisabeth Daldrup-Link1*- 1Radiology, Stanford University, Stanford, CA, United States
- 2The Catholic University of Korea Seoul St Mary's Hospital, Seocho-gu, Republic of Korea
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High-dose Methotrexate (HDMTX) can induce neurotoxicity, yet its impact on brain metabolism remains underexplored. This study aimed to assess short-and long-term brain metabolic changes post-HDMTX on 18F-FDG PET/MRI relative to baseline (pre-HDMTX) scans. In this IRB approved, retrospective study, we included 19 children and young adults (3 females and 16 males; age 17.9±4.3 years), with lymphoma (n=13) or osteosarcoma (n=6). All patients underwent 18F-FDG PET/MRI before (baseline) and after HDMTX (>1000 mg/m2). Post-treatment scans were conducted ≤3 months (short-term group, n=11) or >3 months (long-term group, n=8) after completion of HDMTX and were compared with baseline scans. SUVmean and SUVmax of the whole brain cortex and six subregions were measured with PMOD software. A generalized linear regression model was used to evaluate post-pre-HDMTX SUV values differences in whole cortex with p<0.05 and for with of different brain subregions, with p<0.008 after Bonferroni correction. In the short-term group, compared with baseline, both SUVmean (pre-HDMTX vs. post-HDMTX: 5.06 ± 1.62 vs. 6.31 ± 1.71, p < 0.001) and SUVmax (9.16 ± 3.33 vs. 13.25 ± 3.35, p < 0.001) significantly increased in the whole cortex following HDMTX. In contrast, the long-term group showed no significant changes in SUVmean (6.31 ± 1.71 vs. 6.30 ± 1.54, p = 0.1) or SUVmax (12.01 ± 3.53 vs. 11.58 ± 3.07, p = 0.1) after HDMTX. 18F-FDG PET/MRI revealed short-term increases in brain metabolism post-HDMTX compared with baseline, possibly reflecting neuroinflammation. Long-term follow up scans revealed normalization of brain metabolism or decreased brain metabolism compared to baseline, the latter possibly indicating neurotoxicity.
Keywords: cancer survivors, Methotrexate, Neurotoxicity, pediatric oncology, PET
Received: 04 Jul 2025; Accepted: 19 Dec 2025.
Copyright: © 2025 Shokri Varniab, Kim, Von Krüchten, Lokesha, Hawk, Singh, Liang, Lu-Liang, Baratto, Iv and Daldrup-Link. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Heike Elisabeth Daldrup-Link
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