The goal of this phase 0 study was to determine the absorbed doses in tumors and relevant organs after a test injection of [161Tb]Tb-DOTA-LM3 and [177Lu]Lu-DOTATOC in the same cohort of patients with grade 1 and 2 somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Methods: In this randomized, crossover, prospective, single-center, open-label phase 0 study, 8 patients received 1 GBq of [161Tb]Tb-DOTA-LM3 and 1 GBq of [177Lu]Lu-DOTATOC, with a 4-wk interval between injections. Quantitative SPECT/CT imaging was performed 3, 24, 72, and 168 h after administration of each radio pharmaceutical to calculate tumor and organ absorbed doses (3 dimensional dosimetry using a Monte Carlo-based ordered-subset expectation maximization algorithm). Results: After injection of 1 GBq of [161Tb]Tb-DOTA-LM3, SPECT/CT revealed excellent image quality with intense tumor uptake in all patients and a median of the mean effective tumor half-life of 103 h (range, 56-152 h) for [161Tb]Tb-DOTA-LM3 and 83 h (range, 30-122 h) for [177Lu]Lu-DOTATOC (P 5 0.012). The medians of the mean tumor absorbed doses of [161Tb]Tb-DOTA-LM3 and [177Lu]Lu-DOTATOC were 36.6 Gy/GBq (range, 15-196 Gy/ GBq) and 7.0 Gy/GBq (range, 2.4-14.2 Gy/GBq), respectively (P 5 0.008). The median kidney and bone marrow absorbed doses were 2.4 Gy/GBq (range, 1.8-3.1 Gy/GBq) and 0.31 Gy/GBq (range, 0.24-0.48 Gy/GBq) for [161Tb]Tb-DOTA-LM3 and 0.6 Gy/GBq (range, 0.4-0.8 Gy/GBq) and 0.04 Gy/GBq (range, 0.03-0.06 Gy/GBq) for [177Lu]Lu-DOTATOC, respectively (both P 5 0.008). According to Common Terminology Criteria for Adverse Events version 5.0, grade 1-3 treatment-emergent adverse events occurred in 6 of 8 patients after administration of 1 GBq of [161Tb]Tb-DOTA-LM3. Conclusion: [161Tb]Tb-DOTA-LM3 showed a 7.6-fold-higher median tumor absorbed dose than that of [177Lu]Lu-DOTATOC. The tumor-to-bone marrow absorbed dose ratio was in the same range for [161Tb]Tb-DOTA-LM3 as for [177Lu]Lu-DOTATOC. The administration of 1 GBq of [161Tb]Tb-DOTA-LM3 was safe for all patients, without relevant adverse events.
Purpose Deauville Score (DS) assessment from [18F]FDG PET/CT in multiple myeloma (MM) relies on visual interpretation, limiting reproducibility. This study aimed to develop an automated pipeline for standardised DS computation, evaluate the prognostic value of DS at five anatomical sites, and predict progression-free survival (PFS) by integrating DS with copy number alterations (CNA) and clinical variables.Methods A retrospective cohort of 165 newly diagnosed MM patients with baseline FDG PET/CT, CNA profiling, and blood tests was analysed. An automated pipeline computed DS fully automatically for vertebral bone marrow (BM) and long bones (LB), and semi-automatically for focal (FL), paramedullary (PM), and extramedullary (EM) lesions. DS were subdivided into absent (1), low (2-3), and high (4-5) groups and compared via log-rank test. A penalised Cox model with 12 covariates (five DS, three CNAs, haemoglobin, platelet count, age, sex) was evaluated via nested cross-validation for PFS prediction. For inference on individual prognostic contributions, an unpenalised multivariable Cox model was fitted on the full cohort.Results In univariate analyses, high LB, PM and EM DS were significantly associated with shorter PFS. The penalised Cox model achieved a C-index of 0.710 [95% CI: 0.689-0.732] in predicting the risk of progression. In the multivariable analysis, age, haemoglobin, BM DS, PM DS and amp(1q) were identified as independent prognostic factors.Conclusion Automated DS computation from baseline FDG PET/CT is feasible and, combined with genomic and clinical data, enables a reproducible multimodal approach to prognostic stratification in MM. The pipeline for DS computation is publicly available as an open-source tool (autoDS-PET) at .
Purpose PSMA PET has been proposed for guiding targeted prostate biopsies. As the rate of clinically significant prostate cancer (csPCa) is positively correlated with PSA density (PSAd), a potential application for PSMA-guided biopsies may be men with negative MRI-first (PI-RADS-1-2) but increased PSAd. The PRIMARY scoring system, using the intraprostatic PSMA-pattern was developed and tested using [68Ga]Ga-PSMA-11 and proposed to be universal across PSMA-ligands, however no data on [18F]PSMA-1007 for biopsy guidance exists. Thus, the aim of this study was to evaluate the PRIMARY score for prostate biopsy guidance using [18F]PSMA-1007 in a prospective clinical setup.Methods 91 patients were prospectively enrolled for [18F]PSMA-1007 PET/MRI, 86 of these for biopsy guidance after negative MRI or non-csPCa biopsies from PI-RADS 3-5 lesions and persistent suspicion of csPCa. Transperineal MRI/ultrasound fusion target biopsies were performed predominantly from PRIMARY 3-5 lesions. Nine patients with PRIMARY 1-2 did not undergo target biopsies. CsPCa was defined as ISUP grade >= 2.Results In a per patient analysis, 23.3% (20/86) were diagnosed with csPCa. In line with previous studies, the rate of csPCa increased with higher PRIMARY score in a per lesion analysis, constituting 0% (0/1), 0% (0/8), 7.2% (7/97), 60% (15/25), and 60% (6/10) for PRIMARY 1, 2, 3, 4, and 5 lesions, respectively. The 7.2% PRIMARY-3 lesions containing csPCa exhibited common characteristics such as anterior location or lack of well-defined separation from the peripheral zone.Conclusion We evaluated the PRIMARY score for use with [& sup1;F-8]PSMA-1007 and identified benign features and potential "red flags" for PRIMARY-3 lesions. We found csPCa in 23.3% of patients with negative MRI or non-csPCa biopsies from PI-RADS 3-5 lesions and persistent suspicion of csPCa.
Purpose We aimed to evaluate the diagnostic performance of & sup1;F-8-FDG PET/CT-derived radiomics-based machine learning models for differentiating malignant from benign pancreatic lesions, to compare these models with two sequential stages of visual assessment, and to assess whether incorporation of clinician judgement as a model input provides additional diagnostic gain.Methods In this retrospective single-centre study, 853 consecutive patients who underwent & sup1;F-8-FDG PET/CT between April 2009 and February 2025 for known or suspected pancreatic lesions were screened, and 466 were included in the final analysis. Final diagnosis was established by histopathology (76.9%) or clinico-radiological follow-up (23.1%). Diagnostic performance was assessed within a five-stage framework consisting of two visual assessment stages and three progressively expanded machine-learning stages. The visual stages comprised first-look assessment based on PET/CT images alone and comprehensive second-look assessment integrating available clinical, laboratory, and multimodal imaging data. The machine-learning stages comprised a hybrid PET + CT radiomics model, an integrated model additionally incorporating clinical, laboratory, semiquantitative PET, and imaging-derived variables, and a human-radiomics synergistic model including the clinician's second-look binary judgement as an input feature. PET-only and CT-only radiomics models were also evaluated as unimodal comparators. Radiomic features were extracted after manual three-dimensional segmentation using 3D Slicer/PyRadiomics, and Random Forest was selected as the final classifier.Results Of 466 lesions, 336 (72.1%) were malignant and 130 (27.9%) were benign. First-look visual assessment achieved 93.5% sensitivity, 49.2% specificity, and 81.1% accuracy. Comprehensive second-look assessment improved performance to 97.9% sensitivity, 76.9% specificity, and 92.0% accuracy. Among radiomics-based models, the hybrid PET + CT model outperformed unimodal approaches, achieving 91.1% sensitivity, 66.7% specificity, and 86.8% accuracy. The integrated model did not improve overall accuracy beyond the hybrid model. The human-radiomics synergistic model achieved the highest sensitivity (98.7%) and overall accuracy (93.3%), whereas comprehensive second-look assessment retained slightly higher specificity and NPV.Conclusion & sup1;F-8-FDG PET/CT radiomics-based machine learning models improved specificity beyond routine first-look visual PET interpretation, approaching the performance of comprehensive second-look visual assessment without requiring additional clinical data. Incorporation of clinician judgement further increased sensitivity, although comprehensive second-look visual assessment by an experienced reader retained the highest specificity and NPV among all approaches. These findings support a complementary, decision-support role for radiomics-based models alongside, rather than in place of, expert visual assessment.
Purpose To evaluate the feasibility, safety, and preliminary efficacy of systemic targeted alpha therapy with [& sup2;& sup2;Ac-5]-PSMA in patients with recurrent high-grade glioma (HGG). Glioblastoma multiforme (GBM) and HGGs are highly aggressive primary brain tumors with limited treatment options at recurrence. Expression of prostate-specific membrane antigen (PSMA) in the neovasculature of GBM provides a promising target for radioligand therapy using alpha emitters such as Actinium-225.Methods Four patients with histologically confirmed recurrent HGG received [& sup2;& sup2;Ac-5]-PSMA therapy at a dose of 100 kBq/kg per cycle. Diagnoses were established according to the WHO classification available at the time of diagnosis. The cohort included three patients with GBM and one patient with a high-grade diffuse glial tumor, WHO grade III. Treatment cycles were intended at 8-12-week intervals. Baseline and follow-up assessments were performed visually and then semi-quantitave parameters were described on [Ga-6(8)]-PSMA PET/MRI or PET/CT images also using contrast-enhanced MRI. Clinical status and hematologic parameters were monitored throughout therapy and follow-up.Results While every patient ultimately developed progressive disease following treatment, the predefined PSMA-avid index lesion regressed in one patient and remained stable in another. No grade >= 3 adverse events attributable to [& sup2;& sup2;Ac-5]-PSMA or treatment-related mortality were observed. Low-grade toxicity was limited and mainly consisted of mild xerostomia.Conclusion Systemic [& sup2;& sup2;Ac-5]-PSMA therapy appeared feasible and well tolerated, showing preliminary evidence of disease control in recurrent HGGs.
