Abstract Background: Erythropoietin-producing hepatocellular receptor A2 (EphA2) is a tyrosine kinase receptor overexpressed in multiple solid tumors including pancreatic, bladder, head and neck, breast, colon, prostate, and lung cancers. EphA2 is associated with increased severity, metastatic disease and poor clinical prognosis. Following successful preclinical optimization of a phage display-derived EphA2-specific bicyclic peptide1, this study outlines the first in-human application of EphA2-targeting [68Ga]Ga-BCY18469 in PET/CT imaging. Methods: Preclinical characterization of the EphA2-targeting bicyclic peptide BCY18469 was conducted by assessing stability, binding affinity, internalization, biodistribution and μPET/MR imaging in EphA2+ HT1080 and EphA2- MCF-7 xenograft tumor-bearing nude mice. For clinical translation, seven patients with histologically confirmed pancreatic cancer (5 metastatic, 2 newly diagnosed) underwent [68Ga]Ga-BCY18469-PET/CT (compassionate use). Four patients were examined at 15, 30, 45, 60, and 180 min p.i. for biodistribution and dosimetry assessment, three additional patients at 45 min p.i. (172±42 MBq). Time-activity curves were fitted monoexponentially, and dosimetry calculations were done using IDAC-Dose-Software. Results: [68Ga]Ga-BCY18469 demonstrated EphA2-specific binding and internalization, proteolytic stability up to 72 hours, and rapid background clearance with high tumor uptake, thereby enhancing imaging contrast within 30 minutes in mice. In clinical cases, [68Ga]Ga-BCY18469 demonstrated rapid tumor uptake and was predominantly excreted via the kidneys. Notably, hepatic uptake remained favorably low (SUVmean 0.9±0.3 at 45 min p.i). Mean absorbed doses were 0.49 ± 0.24 mGy/MBq (kidneys), 0.14 ± 0.08 mGy/MBq (salivary glands), and 0.016 ± 0.003 mGy/MBq (liver). EphA2-targeted PET imaging successfully detected 13 liver metastases (SUVmax 6.9±3.4), 2 bone lesions (SUVmax 6.1±0.5), 13 lymph node metastases (SUVmax 5.0±1.1), and 2 peritoneal lesions (SUVmax 5.1±0.8). Primary tumor uptake was observed in 6 of 7 patients, albeit with lower intensity compared to liver metastases (SUVmax 4.8±1.6). Two pulmonary foci and 7 liver lesions identified on CT as morphologically consistent with metastases showed no uptake on EphA2-PET. Conclusion: This first-in-human application of EphA2-targeting [68Ga]Ga-BCY18469 demonstrates the feasibility for visualization of EphA2-expressing primary tumors and metastases, which is in line with the preclinical findings. These initial clinical results support further investigation of [68Ga]Ga-BCY18469 as a diagnostic tool with potential to improve tumor characterization and patient management strategies in EphA2-positive cancers. Reference: 1El Fakiri M, et al. Theranostics. 2024 Aug 6;14(12):4701-4712. Citation Format: Ann-Christin Eder, Mohamed A. Omrane, Christoph-Ferdinand Wielenberg, Mohamed El Fakiri, Aikaterini Klotsotyra, Katia Brüggemann, Heiko Becker, Michael Quante, Michael Mix, Anusha Regupathy, Ben Blakeman, Francesca Wood, Gemma E. Mudd, Matthias Eder, Philipp T. Meyer, Martin T. Freitag. Development and first clinical experiences of a phage display derived bicyclic peptide for EphA2-specific PET imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6520.

BACKGROUND:Determination of time-integrated activity (TIA) with a reduced number of imaging sessions is essential for minimizing patient burden and clinical workload in the dosimetry of [177Lu]Lu-PSMA-617. One approach to achieve this is by performing single-time-point (STP) dosimetry. However, STP dosimetry may be associated with significant accuracy errors in certain patients, potentially impacting the reliability of dose calculations. Moreover, the assessment of precision is crucial to evaluating the stability and reliability of estimated doses. PURPOSE:This study aims to investigate the accuracy and precision of few-time-points (FTP) TIA calculation in kidneys for [177Lu]Lu-PSMA-617 using nonlinear mixed-effects modeling (NLMEM). METHODS:Biokinetic data of kidneys from 63 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-PSMA-617 in the first treatment cycle were used. The SPECT/CT measurement was done at time points (TP) 1) (1.8 ± 0.8) h, 2) (18.7 ± 0.9) h, 3) (42.6 ± 1.0) h, 4) (66.3 ± 0.9) h, and 5) (160.3 ± 24.2) h after injection. This study used the sum-of-exponentials function (SOEF) with six parameters, previously selected as the best fit function for the biokinetic data (PMID: 38423787). Reference TIAs (rTIAs) were derived from fitting the SOEF parameters to all-time-points (ATP) data within the NLMEM framework. Estimated TIAs (eTIAs) were calculated by fitting the FTP data, which consist of one-, two-, three-, and four-time points combinations of the biokinetic data. The accuracy of FTP-NLMEM TIA calculations was quantified using the root-mean-square error (RMSE) and mean absolute percentage error (MAPE) of the relative deviation between eTIAs and rTIAs. Precision was assessed from the coefficient of variation (CV) of individual TIA estimates at each optimal time-point combination. RESULTS:For each optimal TP combination, the RMSEs and MAPEs were (11.0 ± 2.5)% and (7.0 ± 2.3)% for TP3, (6.3 ± 1.6)% and (4.8 ± 1.3)% for TP25, (3.9 ± 1.1)% and (2.3 ± 1.0)% for TP135, and (1.4 ± 0.8)% and (0.9 ± 0.8)% for TP1235. The %CV values of individual TIAs for each best TP combination were (17.1 ± 4.9)% for TP3, (8.5 ± 2.4)% for TP25, (6.3 ± 0.9)% for TP135, (5.1 ± 0.6)% for TP1235, and (4.4 ± 0.3)% for ATP. CONCLUSION:The accuracy and precision of various FTP schemes have been determined and can be used to decide on the number of measurements required. Our study showed that incorporating TP3 in FTP dosimetry could lead to a high accuracy and precision of calculated individual TIAs in [177Lu]Lu-PSMA-617therapy.

In patients with Glioblastoma (GBM), Magnetic Resonance (MR) is used for tumour diagnosis and treatment planning. Positron Emission Tomography (PET) with O-(2)-18 F-Fluoroethyl-L-Tyrosine (FET) has been recommended to distinguish local recurrence from radiogenic alterations. However, clinical practice remains hindered by the time and expertise required for tumour and organs-at-risk (OARs) segmentation and the limited evidence of the added value of PET and its restricted availability across clinical centres. This study presents automatic segmentation models and a comprehensive evaluation of PET/MR complementary biological information for recurrent disease definition. The nnU-Net was employed for segmentation using manually defined contours on 1,610 patients from 33 institutions. Model performance was evaluated by Dice-Sørensen-Coefficient (DSC). PET/MR recurrence complementarity was evaluated in 185 patients by Wilcoxon-Signed-Rank test (WSRT), DSC and radiomic features (RF). In RF analysis, MR-Enhancing subregions were classified as MR∩PET or MR-Only, based on overlap with PET. For MR-RF showing significant MR∩PET/MR-Only differences (WSRT), discrimination was further assessed by classifying RF for 3 × 3 × 3-voxel subregions within MR-Enhancing in two volumes (greater/less than the RF cohort median) and evaluating Positive-Predictive-Value and Sensitivity with MR∩PET/MR-Only. Models’ performance in the test set resulted in DSC(MR-Enhancing) = 0.76 ± 0.24, DSC(MR-Edema) = 0.69 ± 0.23, DSC(PET-Uptake) = 0.71 ± 0.20, DSC(Planning-Target-Volume) = 0.93 ± 0.05, DSC(OARs) = 0.70 ± 0.13. Manual MR and FET-PET based GBM recurrence delineations differed significantly in size (p = 0.0497) and location (DSC = 0.45 ± 0.20). From the 37 MR-RF showing significant differences between MR∩PET and MR-Only (p < 0.05), none of the MR-Enhancing based RF-maps allowed spatial identification of PET findings (positive-predictive-value and sensitivity < 0.6). The resulted segmentation models could facilitate PET/MR integration in GBM treatment. PET/MR comparison supports the complementarity of FET-PET.

Current radiotherapy for malignant tumors often adopts a "one-size-fits-all" approach, prescribing the same irradiation dose for patients with similar clinical indications. However, advancements in functional imaging allow for biologically individualized strategies, with dose distribution tailored to the specific tumor biology. This study proposes a novel approach to biologically individualized radiotherapy, exploiting the synergistic combination of the tumor clonogenic cell information from [18F]FDG PET images and radiosensitivity from [18F]fluoromisonidazole (FMISO) PET images. Methods: Twenty-eight patients with head and neck squamous cell carcinoma (HNSCC) were analyzed. Using imaging biomarkers, individualized tumor profiles were obtained from oxygen partial pressure and clonogenic cell density maps derived from [18F]FMISO and [18F]FDG PET, respectively. Dose-escalated radiotherapy plans aiming at 95% tumor control probability (TCP) were generated using automated planning. Plans were assessed for clinical feasibility and expected TCP. Results: Planned dose distributions achieved greater than 90% TCP in all cases. All treatment plans met standard clinical feasibility criteria for the main organs-at-risk constraints, except for the few cases with significant target overlap, demonstrating the overall feasibility of the personalized strategy. Conclusion: The proposed biologically individualized treatment strategy demonstrated feasibility and clinical applicability. Combining [18F]FDG and [18F]FMISO PET imaging potentially shifts the success rate of HNSCC treatment from approximately 60% at 5 y, as reported in the literature, to a projected TCP of 90%. This treatment strategy holds promise for improving patient outcomes through more precise and effective treatment.

Erythropoietin-producing hepatocellular receptor A2 (EphA2) is overexpressed in various malignancies, including pancreatic ductal adenocarcinoma (PDAC), in which it correlates with poor prognosis. Although EphA2 is considered a promising target receptor for theranostic applications, suitable radiotracers for clinical imaging have been lacking. This study reports first clinical experiences with [68Ga]Ga-BCY18469, a bicyclic peptide radiotracer for EphA2-targeted PET imaging. Seven patients with histologically confirmed PDAC (5 after chemotherapy, 2 at initial staging) underwent PET/CT imaging. Four were scanned at 15, 30, 45, 60 and 180 min. and three at 45 min. after injection of [68Ga]Ga-BCY18469. Dosimetry calculations were performed based on organ-specific time-activity curves from whole-body PET acquisitions. Imaging findings were compared with contrast-enhanced CT or MRI (interval: 9–50 days). No adverse events were observed. The kidneys received the highest absorbed dose (0.31 ± 0.02 mGy/MBq), while the effective dose was 0.017 ± 0.002 mSv/MBq. [68Ga]Ga-BCY18469 demonstrated rapid tumor uptake at 15 min. post-injection with predominantly renal excretion. Of 45 total lesions EphA2-PET detected 36 lesions with tracer uptake suspicious for metastasis. 11 of 45 lesions were detected only on EphA2-PET, whereas 9 of 45 lesions were detected only on CT and/or MRI. The tracer identified 13 liver metastases (SUVmax 6.9 ± 3.4) and 13 lymph node metastases (SUVmax 5.0 ± 1.1), among other findings. Our initial clinical experiences demonstrate that [68Ga]Ga-BCY18469 enables safe, rapid, and high-contrast visualization of EphA2-expressing PDAC lesions. These results strongly support further investigation of [68Ga]Ga-BCY18469 as a diagnostic tool for EphA2-positive malignancies.

INTRODUCTION:This computational study evaluates the accuracy of kinetic models and acquisition schemes in dynamic PET imaging using simulations of 18 F-fallypride PET in the human brain on the real-world data. METHODS:We employed a 2-tissue 4-k model to generate ideal tissue curves for three regions (putamen, thalamus, and temporal cortex) and a reference region (cerebellum), incorporating a simulated metabolite-corrected input function. Realistic measurements were simulated over a 240-min PET scan by defining acquisition protocols (frame timings and durations), modeling tracer decay, and adding noise. Distribution volume ratios (DVRs) were calculated using the Logan reference analysis and the simplified reference tissue model (SRTM), the relative error in DVR was also assessed across various acquisition protocols. Rate constants from the 2-tissue model were varied, and Bland-Altman analysis was quantified to determine bias relative to ground-truth DVR. RESULTS:Results indicate that, under low noise conditions, the Logan reference method performed optimally with a protocol involving a 60-min dynamic scan, a 60-min break, a 30-min scan, another 60-min break, and a final 30-min scan. In noisier conditions, the SRTM yielded the best results with a 150-min effective scan time incorporating three breaks. CONCLUSION:These findings highlight the impact of noise and acquisition strategy on model performance, informing optimal PET imaging protocols.

Patients’ diagnosis, treatment and follow-up increasingly rely on multimodality imaging. One of the main limitations for the optimal implementation of hybrid systems in clinical practice is the time and expertise required for applying standardized protocols for equipment quality assurance (QA). Experimental phantoms are commonly used for this purpose, but they are often limited to a single modality and single quality parameter, lacking automated analysis capabilities. In this study, we developed a multimodal 3D-printed phantom and software for QA in positron emission tomography (PET) hybrid systems, with computed tomography (CT) or magnetic resonance (MR), by assessing signal, spatial resolution, radiomic features, co-registration and geometric distortions. Phantom models and Python software for the proposed QA are available to download, and a user-friendly plugin compatible with the open-source 3D-Slicer software has been developed. The QA viability was proved by characterizing a Philips-Gemini-TF64-PET/CT in terms of signal response (mean, µ), intrinsic variability for three consecutive measurements (daily variation coefficient, CoVd) and reproducibility over time (variation coefficient across 5 months, CoVm). For this system, averaged recovery coefficient for activity concentration was µ = 0.90 ± 0.08 (CoVd = 0.6 HU=(951± 12)×density-(944± 15) with variability of slope and y-intercept of (CoVd = 0.4

BACKGROUND:Molecular radiotherapy with [177Lu]Lu-PSMA-617 is an effective treatment for metastatic castration-resistant prostate cancer. Accurate dosimetry is essential for maximizing therapeutic efficacy while minimizing toxicity. However, standard dosimetry requires multiple imaging sessions, posing logistical challenges. Single-time-point (STP) dosimetry offers a practical alternative but remains challenging for tumor kinetics due to high inter-patient variability. Nonlinear mixed-effects (NLME) modeling, combined with population-based model selection (PBMS), has demonstrated potential for improving STP dosimetry accuracy. PURPOSE:The purpose of this study was to evaluate the accuracy of STP tumor dosimetry using SPECT/CT data, PBMS, and an NLME model in a large population with diverse biokinetic measurements for [177Lu]Lu-PSMA-617 therapy. METHODS:Biokinetic data for [177Lu]Lu-PSMA-617 in tumors were obtained from forty-nine patients with metastatic castration-resistant prostate cancer using SPECT/CT at time points (1.80 ± 0.80), (18.67 ± 0.90), (42.63 ± 1.03), (66.27 ± 0.96), and (159.02 ± 23.35) h after injection. Ten different functions, derived from various parameterizations of two- to four-exponential functions, were fitted to the data using the NLME framework. Each function's parameters were defined as a combination of fixed and random effects. A PBMS approach was employed, using goodness-of-fit tests and Akaike weights to identify the function best supported by the data. The selected function from the NLME fitting of all time points with the leave-one-out method was used to calculate the reference time-integrated activities per volume (TIAVs). The parameters from STP fitting were used to calculate the STP TIAVs. Additionally, STP dosimetry was performed using the Hänscheid method to calculate the TIAVs. Relative deviations (RDs) and root-mean-square errors (RMSEs) were used to analyse the accuracy of the calculated STP TIAVs and Hänscheid method TIAVs compared with the reference TIAVs. RESULTS:The function f 4 b ( t ) = A 1 e - ( λ 1 + λ phys ) t + A 2 e - ( λ phys ) t - ( A 1 + A 2 ) e - ( λ 2 + λ phys ) t ${{f}_{4{\mathrm{b}}}}\ ( {\mathrm{t}} ) = {{{\mathrm{A}}}_1}\ {{{\mathrm{e}}}^{ - ( {{{{{\lambda}}}_1} + {{{{\lambda}}}_{{\mathrm{phys}}}}} ){\mathrm{t}}}} + {{{\mathrm{A}}}_2}{{{\mathrm{e}}}^{ - ( {{{{{\lambda}}}_{{\mathrm{phys}}}}} ){\mathrm{t}}}} - ( {{{{\mathrm{A}}}_1} + {{{\mathrm{A}}}_2}} ) {{{\mathrm{e}}}^{ - ( {{{{{\lambda}}}_2} + {{{{\lambda}}}_{{\mathrm{phys}}}}} ){\mathrm{t}}}}$ was selected as the fit function most supported by the data with an Akaike weight of 93%. For STP dosimetry, a single SPECT/CT measurement at time point 4 (66.3 ± 0.9 h) after injection showed a relatively low mean RD of 0.5% ± 11.0% and median RD of -0.6%. The RMSEs for the STP TIAVs RDs for time points 1-5 were 53%, 29%, 17%, 11%, and 38%, respectively. The STP tumor dosimetry using the PBMS NLME method outperformed the Hänscheid method for all investigated time points. CONCLUSION:Our findings demonstrate that a single SPECT/CT measurement at 3 days after injection may be used to estimate tumor TIAVs in [177Lu]Lu-PSMA-617 therapy using the NLME method and PBMS.

Membrane type 1 matrix metalloproteinase (MT1-MMP) is a pivotal enzyme involved in extracellular matrix remodeling, contributing to tumor invasion, metastasis, and poor prognosis in various cancers, including non-small cell lung, urothelial, pancreatic, gastric, and breast cancers. This study outlines the preclinical development and first in-human application of a phage display-derived MT1-MMP-specific bicyclic peptide, [68Ga]Ga-BCY25286, as a radiotheranostic agent for PET/CT imaging. The MT1-MMP-targeting bicyclic peptide BCY25286 was radiolabeled with either Ga-68 or Lu-177 and subsequently characterized for stability, binding affinity, and internalization. Preclinical evaluation included biodistribution and μPET/MR imaging in MT1-MMP+ HT1080 and MT1-MMP- MCF-7 xenograft tumor-bearing nude mice. For clinical translation, a 65-year-old patient with advanced pulmonary adenocarcinoma underwent [18F]FDG-PET/CT followed by [68Ga]Ga-BCY25286 PET/CT imaging, with PET scans performed after 60 minutes for [18F]FDG and up to 60 minutes for [68Ga]Ga-BCY25286 (compassionate use). Radiolabeling achieved >99% radiochemical purity for both radionuclides. [68Ga]Ga-BCY25286 demonstrated highly MT1-MMP-specific binding (7.2 ± 1.6 nM), proteolytic stability up to 72 hours, and rapid background clearance, thereby enhancing imaging contrast within 30 minutes. In mice, the tracer demonstrated high tumor uptake (10.6 ± 1.1 %ID/g at 1 h p.i.) with persistence up to 24 hours. In the clinical case, [68Ga]Ga-BCY25286 PET/CT imaging revealed high uptake in both primary and biopsy-confirmed metastatic sites, corroborating the findings of [18F]FDG-PET. SUVmaxvalues were comparable for lymph node metastases but higher for bone metastases in MT1-MMP-PET compared to [18F]FDG-PET, with significant kidney retention due to renal excretion. This first-in-human application of MT1-MMP-targeting [68Ga]Ga-BCY25286 demonstrates the feasibility for visualization of MT-1-MMP-expressing primary tumors and metastases, which is in line with the preclinical findings. These initial clinical results support further investigation of [68Ga]Ga-BCY25286 as a diagnostic tool with potential to improve tumor characterization and patient management strategies in MT1-MMP-positive cancers. Ann-Christin Eder, Mohamed A. Omrane, Anusha R. Regupathy, Mohamed El Fakiri, Nils Steinacker, Lisa-Charlotte Domogalla, Christoph-Ferdinand Wielenberg, Michael Mix, Johanna Lahdenranta, Ben Blakeman, Francesca Wood, Philip Huxley, Gemma E. Mudd, Matthias Eder, Philipp T. Meyer, Martin T. Freitag. Development and clinical translation of a phage display derived MT1-MMP-specific bicyclic peptide for radiotheranostic applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4601.

This retrospective single-center study evaluated and compared the prognostic value of distribution parameters of standardized uptake value (SUV) in whole-body tumor volume (WTV) on PSMA PET/CT prior to 177Lu-PSMA radioligand therapy (PSMA RLT) for early treatment response and overall survival (OS). For 59 patients with metastatic castration-resistant prostate cancer baseline clinical and PSMA PET/CT characteristics (Gleason score, time-to-therapy, age, PSA, prior therapies, metastasis sites, WTV) and SUV distribution parameters in WTV (SUVmean, SUVmedian, SUVmax, skewness, kurtosis and interquartile range (IQR)) prior to PSMA RLT were retrospectively collected. The prognostic value for early biochemical and/or imaging progression (PD) (according to PCWG3 and RECIP) as well as OS was evaluated using univariate logistic or Cox regression. SUV distribution parameters significant in univariate analyses were further evaluated using multivariate logistic or Cox regression adjusted for significant baseline characteristics. Model performance was assessed by cross-validation (5-folds, 10 repeats), quantified by area under the curve (AUC) and Harrell’s C, and compared with Wilcoxon signed-rank tests. Addition of other parameters into a regression model was assessed with likelihood ratio tests. 31 patients (53

BACKGROUND:O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET has a higher specificity than contrast-enhanced T1-weighted MRI (CE-T1MRI) in diagnosing recurrent glioblastoma. We aimed to evaluate whether a FET-PET-based target volume delineation, compared with CE-T1MRI, improves outcomes in patients with recurrent glioblastoma scheduled for re-irradiation. METHODS:GLIAA was a multicentre, open-label, parallel randomised study done in 15 radiation oncology centres in Germany. Patients aged 18 years or older with a Karnofsky performance score greater than 60% and a macroscopic WHO grade IV recurrent glioblastoma (1-6 cm) were randomly assigned (1:1) to receive either FET-PET-based or CE-T1MRI-based target volume delineation followed by re-irradiation with 39 Gy in 13 fractions. Randomisation was performed centrally, using a minimisation technique with a random element and a computer-assisted randomisation tool, stratified by time since first radiotherapy, previous chemotherapy, tumour diameter, MGMT status, and planned chemotherapy. The primary endpoint was progression-free survival from randomisation, assessed in the per-protocol population (patients who initiated treatment per their assigned group). Adverse events were systematically assessed in all patients who commenced therapy. The trial was registered with ClinicalTrials.gov (NCT01252459), German Clinical Trials Registry (DRKS00000634), and European Clinical Trials Database (EudraCT 2012-001121-27), and is completed. FINDINGS:Between Nov 22, 2013, and Aug 18, 2021, 271 patients were recruited and screened for eligibility, 200 of whom were randomly assigned to re-irradiation based on FET-PET (n=100) or CE-T1MRI (n=100). 85 (43%) participants were female and 115 (58%) were male. 98 patients in the FET-PET group and 97 in the CE-T1MRI group were treated per protocol. Median follow-up for censored patients was 12·2 months (IQR 6·6-20·7). Median progression-free survival was 4·0 months (95% CI 3·7-5·2) in the FET-PET group and 4·9 months (3·7-6·0) in the CE-T1MRI group (one-sided stratified log-rank p=0·98; adjusted hazard ratio 1·14 [95% CI 0·85-1·52]; p=0·39; median follow-up for six censored patients 4·1 months [IQR 2·3-6·6]). The most common grade 3-4 adverse event was radionecrosis (eight [8%] of 99 in the FET-PET group vs seven [7%] of 99 in the CE-T1MRI group). Acute and subacute serious adverse events occurred in 15 (15%) of 99 patients in each group; possibly re-irradiation-related late serious adverse events occurred in ten (10%) of 97 patients in the FET-PET group and 18 (19%) of 96 in the CE-T1MRI group. There were no treatment-related deaths. INTERPRETATION:FET-PET-based target volume delineation for re-irradiation did not lead to a significant clinical benefit compared with CE-T1MRI-based treatment in patients with recurrent glioblastoma. Thus, CE-T1MRI remains the preferred delineation method in this setting. FUNDING:Deutsche Krebshilfe.

In this study we examined the correlation between standardized uptake value (SUV) of [18F]fluorodeoxyglucose (FDG) and apparent diffusion coefficient (ADC) within the gross tumor volume (GTV) of patients with head and neck squamous cell carcinoma (HNSCC). In addition, we assessed the comparability of cell density (ρ) estimates obtained from FDG PET and MRI data. Twenty-one HNSCC patients from a prospective FMISO imaging trial underwent pre-treatment PET/CT and MRI. We assessed correlations between FDG SUV (mean, max) and ADC (mean, min) within the GTV using Pearson’s correlation coefficient. The tumor cell density within the GTV was calculated from FDG SUV and from ADC maps. For the estimation of ADC-based cell density, we used a published tumor cell volume fraction (vTC). Agreement between FDG- and ADC-derived cell density estimates was assessed. The best-fitting vTC* was computed to achieve equal mean ρADC and ρFDG for each patient and was compared to the literature. The SUV and ADC metrics showed up to moderate negative correlations, but none of them were statistically significant at p < 0.05. The correlation of SUVmean vs. ADCmean with Pearson’s correlation coefficient r = −0.426 and p = 0.054 and SUVmax vs. ADCmin with r = −0.414 and p = 0.062 suggested a weak negative trend. The average and standard deviation of mean ρFDG and ρADC across our cohort were (1.8 ± 0.6) × 108 cells/ml and (3.3 ± 0.2) × 108 cells/ml. The difference between the mean ρFDG and ρADC was statistically significant (p < 0.001). To achieve equal mean ρADC and ρFDG for each patient, the mean optimal vTC* with standard deviation was 0.29 ± 0.09. Although significantly lower than the published mean vTC​ (0.54), vTC* lies within the published range of vTC for HNSCCs (0.28 to 0.75). ADC and SUV metrics exhibited moderate but marginally insignificant correlation in this dataset. Although not directly interchangeable, the two methods provide comparable, clinically relevant cell density estimates, offering flexibility to use the most accessible modality for individualized treatment planning. Registered at German Clinical Trials Register on 20/08/2015 (DRKS00003830).