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Purpose [177Lu]Lu-lilotomab satetraxetan, a novel CD37 directed radioimmunotherapy (RIT), has been investigated in a first-in-human phase 1/2a study for relapsed indolent non-Hodgkin lymphoma. In this study, new methods were assessed to calculate the mean absorbed dose to the total tumor volume, with the aim of establishing potential dose–response relationships based on 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET) parameters and clinical response. Our second aim was to study if higher total tumor burden induces reduction in the 177Lu-lilotomab satetraxetan accumulation in tumor. Procedures Fifteen patients with different pre-dosing (non-radioactive lilotomab) regimens were included and the cohort was divided into low and high non-radioactive lilotomab pre-dosing groups for some of the analyses. 177Lu-lilotomab satetraxetan was administered at dosage levels of 10, 15, or 20 MBq/kg. Mean absorbed doses to the total tumor volume (tTAD) were calculated from posttreatment single-photon emission tomography (SPECT)/computed tomography (CT) acquisitions. Total values of metabolic tumor volume (tMTV), total lesion glycolysis (tTLG) and the percent change in these parameters were calculated from FDG PET/CT performed at baseline, and at 3 and 6 months after RIT. Clinical responses were evaluated at 6 months as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). Results Significant decreases in tMTV and tTLG were observed at 3 months for patients receiving tTAD ≥ 200 cGy compared to patients receiving tTAD p = .03 for both). All non-responders had tTAD tTAD were observed in responders. Reduction in 177Lu-lilotomab satetraxetan uptake in tumor volume was not observed in patients with higher baseline tumor burden (tTMV). Conclusion tTAD of ≥ 200 cGy may prove valuable to ensure clinical response, but further studies are needed to confirm this in a larger patient population. Furthermore, this work indicates that higher baseline tumor burden (up to 585 cm3) did not induce reduction in radioimmunoconjugate accumulation in tumor.

Determining the most informative features for predicting the overall survival of patients diagnosed with high-grade gastroenteropancreatic neuroendocrine neoplasms is crucial to improve individual treatment plans for patients, as well as the biological understanding of the disease. Recently developed ensemble feature selectors like the Repeated Elastic Net Technique for Feature Selection (RENT) and the User-Guided Bayesian Framework for Feature Selection (UBayFS) allow the user to identify such features in datasets with low sample sizes. While RENT is purely data-driven, UBayFS is capable of integrating expert knowledge a priori in the feature selection process. In this work we compare both feature selectors on a dataset comprising of 63 patients and 134 features from multiple sources, including basic patient characteristics, baseline blood values, tumor histology, imaging, and treatment information. Our experiments involve data-driven and expert-driven setups, as well as combinations of both. We use findings from clinical literature as a source of expert knowledge. Our results demonstrate that both feature selectors allow accurate predictions, and that expert knowledge has a stabilizing effect on the feature set, while the impact on predictive performance is limited. The features WHO Performance Status, Albumin, Platelets, Ki-67, Tumor Morphology, Total MTV, Total TLG, and SUVmax are the most stable and predictive features in our study.

Osteosarcoma patients with overt metastases at primary diagnosis have a 5-year survival rate of less than 20%. TP-3 is a murine IgG2b monoclonal antibody with high affinity for an epitope residing on the p80 osteosarcoma cell surface membrane antigen. The tumor-associated antigen p80 is overexpressed in osteosarcomas, and has very low normal tissue expression. We propose a novel dual alpha targeting solution containing two radionuclides from the same decay chain, including the bone-seeking 224Ra, and cancer cell-surface seeking 212Pb-TCMC-TP-3 for the treatment of osteoblastic bone cancers, circulating cancer cells and micrometastases. In this in vitro study, the cytotoxic effects of 212Pb-TCMC-TP-3 (single alpha solution) and 224Ra/212Pb-TCMC-TP-3 (dual alpha solution) were investigated in a multicellular spheroid model mimicking micrometastatic disease in osteosarcoma. OHS spheroids with diameters of 253 ± 98 μm treated with 4.5, 2.7, and 3.3 kBq/ml of 212Pb-TCMC-TP-3 for 1, 4, and 24 h, respectively, were disintegrated within 3 weeks. The 212Pb-TCMC-TP-3 induced a 7-fold delay in spheroid doubling time compared to a 28-times higher dose with the non-specific 212Pb-TCMC-rituximab. The 224Ra/212Pb-TCMC-TP-3 completely disintegrated spheroids with diameters of 218–476 μm within 3 and 2 weeks after 4 and 24 h incubation with 5 kBq/ml, respectively. Treatment with 1 kBq/ml of 224Ra/212Pb-TCMC-TP-3 for 24 h caused an 11.4-fold reduction in spheroid viability compared with unconjugated 224Ra/212Pb. The single and dual alpha solutions with TP-3 showed cytotoxicity in spheroids of clinically relevant size, which warrant further testing of the dual alpha solution using in vivo osteosarcoma models.

BackgroundAdoptive cellular therapy (ACT) with genetically modified T cells aims to redirect T cells against resistant cancers through introduction of a T cell receptor (TCR). The Radium-4 TCR was isolated from a responding patient in a cancer vaccination study and recognizes the enzymatic component of human Telomerase Reverse Transcriptase (hTERT) presented on MHC class II (HLA-DP04). hTERT is a constitutively overexpressed tumor-associated antigen present in most human cancers, including non-small-cell lung cancer (NSCLC), which is the second most common type of cancer worldwide. Treatment alternatives for relapsing NSCLC are limited and survival is poor. To improve patient outcome we designed a TCR-based ACT study targeting hTERT.MethodsT-RAD is a phase I/II study to evaluate the safety and efficacy of Radium-4 mRNA electroporated autologous T cells in the treatment of metastatic NSCLC with no other treatment option. Transient TCR expression is applied for safety considerations. Participants receive two intravenous injections with escalating doses of redirected T cells weekly for 6 consecutive weeks. Primary objectives are safety and tolerability. Secondary objectives include progression-free survival, time to progression, overall survival, patient reported outcomes and overall radiological response.DiscussionTreatment for metastatic NSCLC is scarce and new personalized treatment options are in high demand. hTERT is a tumor target applicable to numerous cancer types. This proof-of-concept study will explore for the first time the safety and efficacy of TCR mRNA electroporated autologous T cells targeting hTERT. The T-RAD study will thus evaluate an attractive candidate for future immunotherapy of solid tumors.

A positive fluorine-18 labelled 2-deoxy-2-fluoroglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has been associated with more aggressive disease and less differentiated neuroendocrine neoplasms (NEN). Although a high maximum standardized uptake value (SUVmax) predicts poor outcome in NEN, volumetric parameters from [18F]FDG PET have not been evaluated for prognostication in a pure high-grade gastroenteropancreatic (GEP) NEN cohort. In this retrospective observational study, we evaluated the volumetric PET parameters total metabolic tumour volume (tMTV) and total total lesion glycolysis (tTLG) for independent prognostication of overall survival (OS). High-grade GEP NEN patients with [18F]FDG PET/CT examination and biopsy within 90 days were included. Total MTV and tTLG were calculated using an adaptive thresholding software. Patients were dichotomised into low and high metabolic groups based on median tMTV and tTLG. OS was compared using Kaplan–Meier estimator and log-rank test. Uni and multivariable Cox regression was used to estimate effect sizes and adjust for tumour differentiation and SUVmax. Sixty-six patients (median age 64 years) were included with 14 NET G3 and 52 NEC cases after histological re-evaluation. Median tMTV was 208 cm3 and median tTLG 1899 g. Median OS in the low versus high tMTV-group was 21.2 versus 5.7 months (HR 2.53, p = 0.0007) and 22.8 versus 5.7 months (HR 2.42, p = 0.0012) in the tTLG-group. Adjusted for tumour differentiation and SUVmax, tMTV and tTLG still predicted for poor OS, and both tMTV and tTLG were stronger prognostic parameters than SUVmax. Both regression models showed a strong association between volumetric parameters and OS for both neuroendocrine tumours (NET) G3 and neuroendocrine carcinomas (NEC). OS for the tTLG low metabolic NEC was much higher than for the tTLG high metabolic NET G3 (18.3 vs. 5.7 months). High-grade GEP NEN patients with high tMTV or tTLG had a worse OS regardless of tumour differentiation (NET G3 or NEC). Volumetric PET parameters were stronger prognostic parameters than SUVmax. publishedVersion

Applications of various positron emission tomography (PET) tracers for assessing atherosclerosis have been evolving over the years. 18F-fluorodeoxyglucose (FDG)-PET was introduced in 2001 as a probe for this purpose. During the past decade, numerous papers have described a major role for sodium 18F-fluoride (NaF) as another tracer for assessing this vascular disease. We have reviewed the existing data about the merits of both techniques for assessing atherosclerosis. We have to emphasize that our team has been actively involved in conducting research with both tracers over many years. In this review, we have relied upon the data from the CAMONA study which has become a gold standard for defining the role of PET imaging in atherosclerosis. This study was one of the largest of any in recent years and has allowed comprehensive comparison between these two tracers in detecting and quantifying atherosclerosis. Based on what we have learned from this major undertaking, we believe the role of FDG-PET will be limited in assessing atherosclerosis in clinical work-up. This is relevant to both major and coronary arteries. In contrast to NaF-PET, the role of FDG-PET in assessing coronary artery atherosclerosis is almost non-existent. Based on the existing data in this domain, NaF-PET is an ideal imaging modality for both research and clinical assessment of atherosclerosis. The aim of this review is to describe the pros and cons of both approaches based on the existing data in the literature.

The PET tracer 18F-fluciclovine (Axumin) was recently approved in the United States and Europe for men with suspected prostate cancer recurrence following prior treatment. This article summarizes studies where systematic sector-based histopathology was used as reference standard to assess the diagnostic accuracy of the tracer 18F-fluciclovine PET in patients with prostate cancer.

The aim of this study was to assess the risk of atherosclerosis in patients with lung cancer compared to patients with extrapulmonary malignancies using 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). We hypothesized that patients with lung cancer would demonstrate increased FDG uptake in the thoracic aorta compared to patients with extrapulmonary cancers. Thirty-four lung cancer patients (21 male, 13 female, 64.1 ± 12.9 yo) were retrospectively compared to seventy-eight patients with extrapulmonary malignancies (46 male, 32 female, 59.6 ± 12.8 yo). Average maximum standardized uptake value (avgSUVmax) and maximum target-to-blood pool ratio (TBRmax) were measured by mapping regions of interest of the ascending aorta, aortic arch, and descending aorta. Two-tailed Student’s t-test was used to assess the differences in avgSUVmax and TBRmax between the two groups and between smokers and non-smokers. Age and gender distribution between the groups were not statistically different. AvgSUVmax and TBRmax were statistically significant increase in lung cancer patients compared to extrapulmonary cancer patients in the ascending aorta, aortic arch, and descending aorta, suggesting a lung cancer-associated increased risk of atherosclerosis development. AvgSUVmax was not significantly different between smokers and non-smokers in all sections of the thoracic aorta. Moving forward, large, prospective studies that directly compare PET data between different malignancies of different stages will help determine the role of FDG-PET/CT in assessing paraneoplastic vascular disease.

A total of 34 studies of prostate-specific membrane antigen PET in prostate cancer had systematic-sector based histopathology and data for diagnostic accuracy measures. Prostate-specific membrane antigen PET showed overall high specificity, but variable sensitivity, to localize known prostate cancer and detect pelvic lymph node metastases. Sensitivity for the detection of pelvic lymph node metastases is better in the recurrent than in the primary setting.

Psoriatic skin lesions are metabolically active, which makes them candidates for imaging with 18-F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The aim of our study was to correlate FDG-PET findings with Psoriasis Area and Severity Index (PASI) scores, the most widely-used grading system for psoriasis. Thirty-three subjects and a total of 84 FDG-PET/CT scans from a prospective clinical trial [NCT01553058] with >2 months moderate-to-severe psoriasis were included. Subjects underwent whole-body FDG-PET/CT imaging 60 min after intravenous FDG administration, prior to the start of treatment. Scans were repeated 12 weeks and 52 weeks after baseline scans were conducted and after treatment or placebo administration was initiated. Each subject and scan was graded by our “PET-PASI” scoring system, a qualitative review of multi-plane reconstructions for both attenuation-corrected (AC) and non-attenuation-corrected (NAC) PET images. PASI and PET-PASI scores were correlated using Spearman’s rho analysis. Our study demonstrated a significant positive correlation between each subject’s corresponding PET-PASI and PASI scores before and during treatment or placebo administration (r=0.53, P