European Journal of Nuclear Medicine and Molecular Imaging最新文献

Purpose: This phase II study investigates the expression of somatostatin receptors (SSTR) in relapsing and refractory multiple myeloma (rrMM) patients for potential radiotheranostic application.

Methods: Seventeen triple-class exposed rrMM patients who demonstrate [¹⁸F]F-FDG avidity were prospectively included. Patients underwent a [⁶⁸Ga]Ga-DOTATATE PET/CT within 4 weeks after [¹⁸F]F-FDG PET/CT, which was performed as part of the standard workup. Focal lesions (FLs) were identified on both scans and were defined as focal uptake higher than the femoral bone marrow background uptake. Peptide Receptor Radionuclide Therapy (PRRT) eligibility was determined based on the following criteria: absence of [¹⁸F]F-FDG-avid FLs without corresponding [⁶⁸Ga]Ga-DOTATATE uptake, identification of ≥ 3 [⁶⁸Ga]Ga-DOTATATE FLs, and no diffuse bone marrow uptake on [⁶⁸Ga]Ga-DOTATATE PET/CT.

Results: All patients had measurable disease on [¹⁸F]F-FDG PET/CT. [⁶⁸Ga]Ga-DOTATATE uptake was observed in all patients, with FLs identified in 15 of the 17 patients. The combined [¹⁸F]F-FDG and [⁶⁸Ga]Ga-DOTATATE PET/CT analyses classified patients into 4 categories: (1) Identical FLs identified by both radiotracers; (2) All [¹⁸F]F-FDG FLs showed corresponding [⁶⁸Ga]Ga-DOTATATE uptake, with additional [⁶⁸Ga]Ga-DOTATATE FLs; (3) Only some of the [¹⁸F]F-FDG FLs showed [⁶⁸Ga]Ga-DOTATATE uptake; (4) Diffuse bone marrow uptake of [⁶⁸Ga]Ga-DOTATATE, preventing FLs identification. Patients in categories 1 and 2 were deemed PRRT-eligible if they had ≥ 3 FLs on [⁶⁸Ga]Ga-DOTATATE PET/CT. Consequently, 10 out of 17 patients (60%) met the PRRT eligibility criteria.

Conclusion: In heavily pretreated rrMM patients showing avid disease on [¹⁸F]F-FDG PET/CT, [⁶⁸Ga]Ga-DOTATATE PET/CT identified 60% of patients as eligible candidates for PRRT, suggesting a potential new indication for PRRT in selected patients.

Trial registration: NCT04379817, Registered on 4 May 2020, https://clinicaltrials.gov/study/NCT04379817?cond=multiple%20myeloma&term=scarlet&rank=1.

Purpose: Neuroinflammation is a key pathological driver in neurodegenerative diseases, including Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP). Positron emission tomography (PET) with tracers targeting the translocator protein (TSPO) enables the in vivo quantification of microgliosis. TSPO tracers have shown similar disease-specific patterns across cohorts. However, direct quantitative comparisons between commonly used TSPO-PET tracers in tauopathies have not been performed. Here, we apply a TSPO-PET standardization pipeline across clinically matched AD cohorts and PSP cohorts, to quantify, compare and combine multi-centre TSPO-PET data.

Methods: Patients with PSP were scanned with either [¹¹C]PK11195 or [¹⁸F]GE-180 at one of two centres, while patients with AD and control participants were scanned with either [¹¹C]PK11195, [¹⁸F]GE-180 or [¹¹C]PBR28 at one of three centres. A standardised pre-processing pipeline was implemented and participant standardised uptake volume ratio (SUVR) values were z-scored using tracer-specific control participant values. In a data-driven approach, dissimilarity analyses were employed to assess differences between tracers across clinically matched cohorts.

Results: In PSP, dissimilarity analysis suggested that [¹¹C]PK11195 and [¹⁸F]GE-180 binding patterns were comparable following standardisation. In AD, comparability across tracers was less robust, with [¹¹C]PK11195 and [¹⁸F]GE-180 being most comparable, followed by [¹⁸F]GE-180 vs. [¹¹C]PBR28, then by [¹¹C]PK11195 vs. [¹¹C]PBR28.

Conclusion: The pipeline was effective at harmonising TSPO-PET tracers and standardising the regional quantification of neuroinflammation in clinically matched cohorts of PSP, while the standardisation pipeline results were less robust across AD cohorts.

Purpose: We aimed to evaluate the safety and efficacy to explore predictors of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA I&T in metastatic castration-resistant prostate cancer (mCRPC) patients aged ≥ 75 and explored baseline predictors of overall survival (OS).

Materials and methods: 56 men (median age 78, range 75-95) were treated with RLT. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Baseline Gleason score, blood parameters (PSA, LDH), and sites of metastases (bone, lymph nodes, liver, lung) were recorded. Quantitative PET parameters such as SUVmean (mean standardized uptake value), SUVpeak (peak standardized uptake value), SUVmax (maximum standardized uptake value), PSMA-TV (PSMApositive tumor volume), TL-PSMA (total lesion PSMA) were measured. PET response was assessed by RECIP 1.0 (response evaluation criteria in PSMA imaging); biochemical response by PCWG3 (prostate cancer working group 3). Associations with OS were analyzed via uni- and multivariable Cox regression and Kaplan-Meier curves.

Results: No CTCAE grade III-V toxicities occurred. Grade I/II hematologic events included anemia (23.2%), leukocytopenia (18.6%) and thrombocytopenia (9.3%); eGFR declined by 2.5% (grade I/II in 18.6%). Median OS was 11 months; 60.7% of patients died. 74.4% of patients (32/43) showed PSA declines (median - 58%; 14/43 ≥ 50%). Higher baseline PSA (HR 1.001 per ng/mL; P < 0.10) and LDH (HR 1.008 per U/L; P < 0.01) were associated with shorter OS. Patients with progressive disease by both RECIP and PCWG3 had shorter OS than others (11 vs. 22 months; HR 3.3; P < 0.01). Any PSA response predicted longer OS (21 vs. 7 months; HR 0.3; P < 0.01). Presence of liver metastases portended poorer survival (8 vs. 21 months; HR 6.7; P < 0.001).

Conclusion: [¹⁷⁷Lu]Lu-PSMA I&T RLT is well tolerated in patients ≥ 75 years. Lower baseline PSA and LDH but not PSMA-TV predict longer OS. Early PSA response strongly correlates with improved survival. Combined use of RECIP and PCWG3 criteria optimizes response assessment.

Purpose: Accurate delineation of tumor margins and maximal safe resection are critical for successful curative oncologic surgery. However, fibroblast activation protein (FAP)-targeted probes suitable for fluorescence imaging remain limited. Here, we developed novel FAP-targeted fluorescent probes to accurately delineate tumor margins and enable rapid intraoperative identification of tumor boundaries in resected specimens.

Methods: DOTA chelator for radiolabelling with gallium-68 was incorporated into dual-modality FAP-targeted probes synthesised by conjugating FAP-2286 and 3BP-3940 with the near-infrared (NIR) fluorophore IRDye800CW. These probes were evaluated both in vitro and in vivo using HEK293T-FAP cells stably expressing FAP and xenograft mouse models. Positron emission tomography (PET) and (NIR-II) fluorescence imaging assessed the specificity and ability of probes to delineate tumor margins. For clinical validation, resected lung tissue was incubated ex vivo with the probes. Tumor regions and margins were identified using fluorescence imaging and subsequently validated by haematoxylin and eosin (H&E) staining and FAP immunohistochemistry.

Results: Both IRDye800CW-FAP-2286 and IRDye800CW-3BP-3940 exhibited high affinity for FAP-positive cells in vitro. PET imaging revealed high tumor specificity for both probes in vivo. In vivo and ex vivo NIR-II fluorescence imaging enabled accurate visualisation of tumor margins, with IRDye800CW-3BP-3940 exhibiting superior performance compared with IRDye800CW-FAP-2286. In the clinical specimen, IRDye800CW-3BP-3940 successfully delineated tumor regions with strong concordance to histopathological findings.

Conclusion: We developed and validated a novel dual-modality molecular probe, IRDye800CW-3BP-3940, which integrated PET and NIR fluorescence imaging capabilities. This probe enabled highly specific detection of FAP-positive tumors and precise delineation of tumor margins in resected specimens.

Purpose: The isocitrate dehydrogenase (IDH) genotype is crucial for diagnosing and managing adult-type diffuse glioma. We investigated spatial tumour characteristics in treatment-naïve glioma using an U-Net-based CNN and evaluated associations with metabolic dysfunction and IDH genotype.

Methods: Between 2015 and 2024 patients with confirmed contrast-enhancing glioma were pre-operatively investigated using MRI or [18 F]FET PET/MRI. Automated morphometry using a U-Net-based CNN on standard MRI sequences (T1c, T1, T2, FLAIR) was performed. Contrast-enhancing tumour fraction (CTF), metabolic tumour volume (MTV), total tumour volume (TTV) were determined. Dice coefficient assessed volume intersections. Comparative and statistical analyses included non-parametric tests, ROC curves, regression, and correlation.

Results: A total of 180 patients (male, 114; female, 66; age, M ± SD = 54 ± 15y; IDH-mutant, 63; IDH wild-type, 117) with treatment-naïve glioma were evaluated. [18 F]FET-PET metabolic activity correlated significantly with CTF (p < .05). IDH-mutant gliomas had lower CTF (p < .001) due to higher non-enhancing tumour mass (p < .001) relative to the enhancing mass, unlike IDH wild-type glioblastoma. The CTF predicted IDH genotype with high accuracy (AUC = 0.85, sensitivity 78%, specificity 90%) across datasets. Combining CTF with patient age or SUVmax further improved the classification (ΔAUC = 0.12, p = .02; ΔAUC = 0.09, p > .05). Subgroup analyses showed consistent performance across IDH-mutant subtypes. MTV from [18 F]FET-PET exceeded structurally apparent TTV (p = .033).

Conclusion: Spatial mapping of treatment-naïve glioma identified a non-invasive biomarker, which is linked to metabolic dysfunction and enabled robust IDH-genotype classification from standard MRI, suggesting a central role for radiogenomic assessment in adult-type diffuse gliomas prior to surgery.