Philipp Tobias Meyer

Background/Objectives: Glioblastoma (GBM) is a hard-to-treat cancer with a 5-year survival rate of 5.7% without significant improvement in the past decades. Personalised strategies based on improved tumour characterisation and treatment-outcome prediction could support treatment adaptation and improve therapeutic efficacy. Magnetic Resonance (MR) is the standard imaging modality for GBM radiotherapy (RT) planning. Positron Emission Tomography (PET) with O-(2)-[^18F]fluoroethyl-L-tyrosine (FET) is recommended for distinguishing recurrence from pseudo-progression. However, evidence on PET|MR complementarity for predicting treatment outcome in recurrent GBM remains limited. Methods: We evaluated FET-PET|MR biomarkers to predict Time-To-Progression (TTP), Overall Survival (OS) and Acute Recurrence (AR) in a prospective cohort of 185 recurrent GBM patients from 15 institutions. T1-weighted contrast-enhanced, Fluid-Attenuation Inversion-Recovery, Apparent-Diffusion-Coefficient maps and FET-PET images were analysed. Gross- and Planning-Target Volumes (GTV/PTV) were manually delineated and the intersection of PET|MR-GTVs was defined as MR∩PET. Radiomics models were developed (5-fold cross-validation) and evaluated in a held-out test set. Additionally, nnUNet was used to predict MR∩PET from MR sequences. Results: MR∩PET volume yielded the highest number of statistically significant models, 15 versus 6 for PET|MR-GTVs and 0 for PET|MR-PTVs. Of these 21 models, 19 required the inclusion of PET imaging. The best-performing models discriminated between short and long OS, with p < 0.0001 in validation and test, and predicted AR, with ROC-AUC(validation) = 0.81 and AUC(test) = 0.63. By combining both models, poor responders (short OS and/or AR) were identified with Sensitivity = 82% and Specificity = 75%. MR-based prediction of MR∩PET showed a Dice Similarity Coefficient (test) = 0.87 ± 0.12. Conclusions: The PET|MR radiomic models derived from our multicentre prospective cohort support the identification of recurrent GBM patients with poor RT outcomes, potentially enabling future personalised strategies for treatment improvement.

Background: Assessment of cerebrovascular reserve capacity (CVRC) is central to treatment planning in adult Moyamoya disease. [¹⁵O]-water-PET with acetazolamide challenge (PET-ACZ) serves as the reference standard but is resource-intensive and not universally available, whereas breathhold BOLD MRI (bh-fMRI) may offer a practical noninvasive alternative for screening and triage. Methods: This retrospective diagnostic accuracy study compared bh-fMRI and PET-ACZ in 67 adult MMD patients (1072 ROIs across 402 supratentorial vascular territories) to determine correlation and clinically useful MRI thresholds for impaired cerebrovascular reserve. Data were analyzed using Pearson’s correlation and ROC curves (STARD-compliant). Cerebellum-normalized percent signal change (CN-PSC) was referenced against PET-ACZ < 66% for pathological CVRC. Results: Supratentorial territories showed strong correlation (r = 0.71, 95%CI 0.62–0.80). Optimal diagnostic threshold was <28.2% CN-PSC on bh-fMRI (Youden index; sensitivity 83.8%, specificity 80.9%, AUROC = 0.87); screening threshold < 60% CN-PSC yielded sensitivity 94.6% and NPV 91.1%. No patient factors (age, Suzuki stage, etc.) influenced agreement (univariate/multivariate analyses). Conclusions: Bh-fMRI supplements PET-ACZ as a screening and diagnostic tool for cerebrovascular reserve impairment in adult MMD. PET remains the reference standard for confirmation, especially in intermediate or discordant cases, and the proposed thresholds (60%: monitor) require prospective validation before routine decision-making use.

Objectives: Fluorescence-guided surgery (FGS) targeting prostate-specific membrane antigen (PSMA) holds promise for improving surgical precision in prostate cancer. Since conjugation of fluorescent dyes to targeting vectors can substantially alter pharmacokinetic properties, we systematically evaluated a library of fluorescent dyes conjugated to a PSMA-617-derived scaffold incorporating sarcosine-based spacers to identify candidates with favorable biodistribution and optical profiles for clinical translation. Methods: Nineteen fluorescent dyes spanning NIR, large Stokes shift, and STED-compatible categories were conjugated to a dual-labeled PSMA-617-derived precursor (Glu-urea-Lys-2Nal-TXA-Sar₁₀-Lys(DOTA)-Sar₅-βAla; hereafter DP). Compounds were radiolabeled with ⁶⁸Ga or ¹⁷⁷Lu and characterized for serum stability, lipophilicity, binding affinity, and internalization in LNCaP^PSMA+ cells. In vivo pharmacokinetics were assessed in LNCaP xenograft-bearing BALB/c nu/nu mice by µPET/MRI (1 and 2 h p.i., 500 pmol ⁶⁸Ga), organ distribution (0.5, 1, and 2 h p.i., 60 pmol ¹⁷⁷Lu), and clinical-grade endoscopic fluorescence imaging. Results: All conjugates retained hydrophilic character (logD: −3.72 to −1.79), low nanomolar binding affinity (K_i: 18–87 nM), and high serum stability (94–100% intact at 24 h). Despite comparable in vitro properties, dye conjugation markedly influenced in vivo pharmacokinetics: tumor uptake at 2 h p.i. ranged from 1 to 23%ID/g and kidney accumulation from 3 to 82%ID/g. Visible-range dyes exhibited faster renal washout within the imaging window and higher tumor-to-background contrast than NIR fluorophores. Fluorescence signal intensity did not correlate with radiotracer-derived uptake, underscoring the importance of dye-specific photophysical properties. Conclusions: DP-12 (SulfoCy5), DP-15 (Alexa Fluor 647), and DP-18 (Tide Fluor 5WS) were identified as lead candidates combining favorable pharmacokinetics with strong fluorescence contrast, warranting further evaluation toward fluorescence-guided prostate cancer surgery.

Background/Objectives: Quantifying cerebrovascular reactivity (CVR) is essential for stroke risk assessment in patients with Moyamoya Angiopathy (MMA). Breath-hold functional MRI (bh-fMRI) is an easily implementable method to assess CVR. Determining the optimal time period of the BOLD signal for analyzing the best bh-fMRI data quality remains an open question. Methods: A retrospective analysis of 46 bh-fMRI data sets of MMA patients was conducted. The percentage BOLD signal changes were evaluated at different time periods (time point of the maximum cerebellar signal peak (TP_{cereb. max}) ± 0 s, TP_{cereb. max} ± 1 s, TP_{cereb. max} ± 2 s, TP_{cereb. max} ± 3 s, TP_{cereb. max} ± 4 s, TP_{cereb. max} ± 5 s). The agreement between the bh-fMRI maps and [¹⁵O]water PET maps was independently and consensually rated on a 4-point Likert scale (1 = poor, 2 = moderate, 3 = good, 4 = excellent) and compared with the Friedman test. The inter-rater agreement was calculated separately for each time period using quadratic weighted Cohen’s kappa κ_w. Results: The selected time period had a significant impact on the agreement between bh-fMRI and [¹⁵O]water PET (χ²(5) = 79.448, p < 0.001, W = 0.345). Short time periods of TP_cereb.max ± 0 s or TP_cereb.max ±1 s demonstrated the highest level of concordance between bh-fMRI and [¹⁵O]water PET (median = 3.5 for TP_cereb.max ± 0 s; median = 3 for TP_cereb.max ± 1 s, modus = 4 in both cases). The agreement between bh-fMRI and [¹⁵O]water PET was significantly higher when evaluating time periods of TP_cereb.max ± 0 s than when evaluating all time periods ≥ TP_{cereb. max} ± 2 s. The inter-rater agreement was almost perfect for all time periods except one (TP_{cereb. max} ± 1 s). Conclusions: Short time periods should be selected when evaluating CVR with bh-fMRI, as this study suggests a high level of validity in comparison to [¹⁵O]water PET.

Purpose: Breath-hold functional MRI (bh-fMRI) is able to quantify cerebrovascular reactivity. Vessel stenoses can lead to delayed hemodynamic responses. We aimed to investigate whether delay correction improves the quality of bh-fMRI compared to the diagnostic standard [¹⁵O]water PET. Methods: The bh-fMRI data sets of 25 patients with Moyamoya Angiopathy were analyzed retrospectively without and with delay correction. Delay correction was calculated using time-to-peak (TTP) maps derived from dynamic susceptibility contrast (DSC) perfusion MRI. [¹⁵O]water PET maps and bh-fMRI maps without and with delay correction were presented blinded for delay correction to two neuroradiologists. The agreement between bh-fMRI without and with delay correction and [¹⁵O]water PET was independently and consensually rated on a 4-point-Likert scale (1 = poor, 2 = moderate, 3 = good, 4 = excellent) and compared with Wilcoxon signed-rank test. Results: The agreement between bh-fMRI and [¹⁵O]water PET without delay correction was good/excellent (median = 3, modus = 4), and improved significantly after delay correction with medium effect size (median = 4, modus = 4, z = -2.121, p = 0.034, r = 0.42). Conclusion: Delay correction improves the quality of bh-fMRI and seems to be helpful in clinical practice.

In October 2024, Europe again experienced a period of shortage of technetium-labeled tracers. In order not to delay time-critical treatments of liver tumors, we turned to ⁶⁸Ga-labeled macroaggregated albumin particles ([⁶⁸Ga]Ga-MAA) as already used for lung perfusion PET imaging for selective internal radiation therapy (SIRT) dosimetry and treatment planning. Labeling was performed under GMP conditions and could be applied for SIRT planning in one patient. Post-therapy dosimetry based on [⁹⁰Y]microsphere PET/CT demonstrated excellent agreement. Dosimetry and treatment planning with [⁶⁸Ga]Ga-MAA should be considered as a viable alternative to [^99mTc]Tc-MAA SPECT/CT and could be considered for routine use.

BACKGROUND: Immune checkpoint inhibitors (ICIs), though revolutionary in cancer treatment, may accelerate atherosclerosis by inducing arterial inflammation. Due to a lack of controlled studies, the capacity of arterial 2-deoxy-2-[ ¹⁸ F]fluoro-D-glucose ([ ¹⁸ F]FDG) uptake in patients with cancer to detect this arterial inflammation remains unclear. METHODS: Arterial [ ¹⁸ F]FDG uptake at 6 anatomic landmarks was assessed on serial positron emission tomography scans in patients with cancer treated at a German University Hospital between January 2010 and May 2023. Patients aged ≥65 years with at least 4 sequential scans within 30 months were included. Linear mixed regression analyses were used to evaluate the change in arterial tracer uptake in patients who received ICI or not. RESULTS: Of the 156 patients included, 50 (30.1%) received ICIs after the baseline scan. Baseline arterial [ ¹⁸ F]FDG uptake correlated with traditional cardiovascular risk factors, such as body mass index and male sex. Cross-sectional analyses suggested a negative effect of cholesterol-lowering medication on arterial [ ¹⁸ F]FDG uptake at follow-up. In a time-dependent interaction analysis, arterial [ ¹⁸ F]FDG uptake increased by 0.8% annually in patients without ICIs (95% CI, 0.2%–1.4%), potentially reflecting the background progression of arterial inflammation in patients with cancer. In ICI users, [ ¹⁸ F]FDG uptake increased by 2.5% annually (95% CI, 1.7%–3.3%; P =0.001 for interaction with no ICI). Higher annual increase rates in ICI users were consistent across several anatomic landmarks, preexisting cardiovascular disease status, arterial calcification status, and concomitant chemotherapy or steroid use. However, this effect did not reach statistical significance in patients with melanoma and those with prior irradiation therapy. CONCLUSIONS: This is the first controlled clinical study supporting the role of ICIs in accelerating atherosclerosis through low-grade arterial inflammation. However, although detectable by repeated [ ¹⁸ F]FDG scans, the increase in tracer uptake associated with ICI use was modest compared with individual variability, questioning whether [ ¹⁸ F]FDG captures the full pathophysiological process of ICI-induced, lymphocyte-driven inflammation.

Background: Preoperative prediction of postoperative pulmonary function after anatomical resection for lung cancer is essential to prevent long-term morbidity and mortality. Here, we compared the accuracy of hybrid single-photon emission computed tomography/computed tomography (SPECT/CT) with traditional anatomical and planar scintigraphy approaches in predicting postoperative pulmonary function in patients with impaired lung function. Methods: We analyzed the predicted postoperative pulmonary function in patients undergoing major anatomical lung resection, applying a segment counting approach, planar perfusion scintigraphy (PPS), and SPECT/CT-based lung function quantification. Results: In total, 120 patients were evaluated, of whom 82 were included in the study. Postoperative lung function tests were obtained in 21 of 82 patients. The preoperative SPECT/CT-based quantification yielded very accurate results compared to the actual postoperative FEV1 and DLCO values. The linear regression analysis showed that the SPECT/CT-based analysis predicted postoperative FEV₁ (%) and D_LCO values more accurately than the segment counting approach or PPS. Accordingly, 58/82 patients would qualify for anatomical lung resection according to the SPECT-based quantification, 56/82 qualified according to the PPS (Mende), and only 47/82 qualified according to the segment counting method. Moreover, we noted that the SPECT-predicted FEV₁ values were very close to the actual postoperative values in emphysema patients, and selected patients even showed improved lung function after surgery. Conclusions: Anatomically driven methods such as SPECT/CT yielded a very accurate prediction of the postoperative pulmonary function. Accordingly, applying SPECT/CT revealed more patients who would formally qualify for lung resection. We suggest SPECT/CT as the preferred method to evaluate eligibility for lung surgery in selected patients with impaired pulmonary reserve.

Before revascularization, moyamoya patients require hemodynamic evaluation. In this study, we evaluated the scoring system Prior Infarcts, Reactivity and Angiography in Moyamoya Disease (PIRAMID). We also devised a new scoring system, MRI-Based Assessment of Risk for Stroke in Moyamoya Angiopathy (MARS-MMA), and compared the scoring systems with respect to the capability to predict impaired [¹⁵O]water PET cerebral perfusion reserve capacity (CPR). We evaluated 69 MRI, 69 DSA and 38 [¹⁵O]water PET data sets. The PIRAMID system was validated by ROC curve analysis with neurological symptomatology as a dependent variable. The components of the MARS-MMA system and their weightings were determined by binary logistic regression analysis. The comparison of PIRAMID and MARS-MMA was performed by ROC curve analysis. The PIRAMID score correlated well with the symptomatology (AUC = 0.784). The MARS-MMA system, including impaired breath-hold-fMRI, the presence of the Ivy sign and arterial wall contrast enhancement, correlated slightly better with CPR impairment than the PIRAMID system (AUC = 0.859 vs. 0.827, Akaike information criterion 140 vs. 146). For simplified clinical use, we determined three MARS-MMA grades without loss of diagnostic performance (AUC = 0.855). The entirely MRI-based MARS-MMA scoring system might be a promising tool to predict the risk of stroke.