Salvage local treatment for recurrent prostate cancer after focal therapy: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the role of salvage local treatment in managing recurrent PCa following FT, focusing on oncological and functional outcomes. METHODS: A systematic review and meta-analysis were performed following the PRISMA framework. A comprehensive literature search using the PubMed/MEDLINE and EMBASE databases was performed until July 2023. Eligible studies included patients with clinically localised PCa initially treated with FT, who experienced relapse during surveillance and subsequently underwent salvage radical prostatectomy (sRP), salvage external beam radiation therapy (sEBRT) or salvage focal therapy (sFT). The primary endpoint was the biochemical recurrence rate post-salvage treatment. The secondary endpoints were functional outcomes, including urinary incontinence and erectile dysfunction rates. RESULTS: In 26 retrospective studies including 990 patients, the overall pooled biochemical recurrence rate postsalvage treatment was 26%. The subgroup analysis revealed a biochemical recurrence rate of 20%, 22%, and 42% after sRP, sEBRT, and sFT, respectively. The overall pooled rate of urinary incontinence was 20%. Salvage FT had the lowest prevalence of urinary incontinence, followed by sRP and sEBRT. The overall pooled rate of erectile dysfunction was 43%. Salvage RP had the highest prevalence of erectile dysfunction, followed by sFT and sEBRT. Substantial heterogeneity was observed among the studies, primarily due to different sample sizes. Meta-regression analysis revealed no to low contributions of salvage treatment modalities, extent of ablation, age, prostatic specific antigen level before salvage treatment, proportion of patients with Gleason score ≥7 at recurrence, and time between the primary and salvage therapies to heterogeneity. CONCLUSION: Salvage local treatment for recurrent PCa after FT is feasible, and it provides acceptable oncological and functional outcomes. Among all treatment modalities, sRP and sEBRT appeared to have the lowest biochemical recurrence rates, whereas sFT was associated with improved functional outcomes.

RNA lipid nanoparticles as efficient in vivo CRISPR-Cas9 gene editing tool for therapeutic target validation in glioblastoma cancer stem cells.

In vitro and ex-vivo target identification strategies often fail to predict in vivo efficacy, particularly for glioblastoma (GBM), a highly heterogenous tumor rich in resistant cancer stem cells (GSCs). An in vivo screening tool can improve prediction of therapeutic efficacy by considering the complex tumor microenvironment and the dynamic plasticity of GSCs driving therapy resistance and recurrence. This study proposes lipid nanoparticles (LNPs) as an efficient in vivo CRISPR-Cas9 gene editing tool for target validation in mesenchymal GSCs. LNPs co-delivering mRNA (mCas9) and single-guide RNA (sgRNA) were successfully formulated and optimized facilitating both in vitro and in vivo gene editing. In vitro, LNPs achieved up to 67 % reduction in green fluorescent protein (GFP) expression, used as a model target, outperforming a commercial transfection reagent. Intratumoral administration of LNPs in GSCs resulted in ~80 % GFP gene knock-out and a 2-fold reduction in GFP signal by day 14. This study showcases the applicability of CRISPR-Cas9 LNPs as a potential in vivo screening tool in GSCs, currently lacking effective treatment. By replacing GFP with a pool of potential targets, the proposed platform presents an exciting prospect for therapeutic target validation in orthotopic GSCs, bridging the gap between preclinical and clinical research.

The Role of Fibroblast Activation Protein in Glioblastoma and Gliosarcoma: A Comparison of Tissue, 68Ga-FAPI-46 PET Data, and Survival Data.

Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68Ga-FAP inhibitor (FAPI)-46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0-3, with higher values indicating stronger expression). Additionally, 68Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue (P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUVmean and SUVpeak of 68Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUVmean and SUVpeak in 68Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis.

Future Perspectives of Artificial Intelligence in Bone Marrow Dosimetry and Individualized Radioligand Therapy.

Radioligand therapy is an emerging and effective treatment option for various types of malignancies, but may be intricately linked to hematological side effects such as anemia, lymphopenia or thrombocytopenia. The safety and efficacy of novel theranostic agents, targeting increasingly complex targets, can be well served by comprehensive dosimetry. However, optimization in patient management and patient selection based on risk-factors predicting adverse events and built upon reliable dose-response relations is still an open demand. In this context, artificial intelligence methods, especially machine learning and deep learning algorithms, may play a crucial role. This review provides an overview of upcoming opportunities for integrating artificial intelligence methods into the field of dosimetry in nuclear medicine by improving bone marrow and blood dosimetry accuracy, enabling early identification of potential hematological risk-factors, and allowing for adaptive treatment planning. It will further exemplify inspirational success stories from neighboring disciplines that may be translated to nuclear medicine practices, and will provide conceptual suggestions for future directions. In the future, we expect artificial intelligence-assisted (predictive) dosimetry combined with clinical parameters to pave the way towards truly personalized theranostics in radioligand therapy.

Human platelet lysate supports SH-SY5Y neuroblastoma cell proliferation and differentiation into a dopaminergic-like neuronal phenotype under xenogeneic-free culture conditions.

SH-SY5Y is a human neuroblastoma cell line that can be differentiated into several neuronal phenotypes, depending on culture conditions. For this reason, this cell line has been widely used as an in vitro model of neurodegenerative conditions, such as Parkinson's disease (PD). However, most studies published to date used fetal bovine serum (FBS) as culture medium supplement for SH-SY5Y cell differentiation. We report on the testing of human platelet lysate (hPL) as a culture medium supplement to support SH-SY5Y cell culture. Both standard hPL and a fibrinogen-depleted hPL (FD-hPL) formulation, which does not require the addition of anticoagulants to culture media, promoted an increase in SH-SY5Y cell proliferation in comparison to FBS, without compromising metabolic activity. SH-SY5Y cells cultured in hPL or FD-hPL also displayed a higher number of neurite extensions and stained positive for MAP2 and synaptophysin, in the absence of differentiation stimuli; reducing hPL or FD-hPL concentration to 1% v/v did not affect cell proliferation or metabolic activity. Furthermore, following treatment with retinoic acid (RA) and further stimulation with brain-derived neurotrophic factor (BDNF) and nerve growth factor beta (NGF-ß), the percentage of SH-SY5Y cells stained positive for dopaminergic neuronal differentiation markers (tyrosine hydroxylase [TH] and Dopamine Transporter [DAT]) was higher in hPL or FD-hPL than in FBS, and gene expression of dopaminergic markers TH, DAT, and DR2 was also detected. Overall, the data herein presented supports the use of hPL to differentiate SH-SY5Y cells into a neuronal phenotype with dopaminergic features, and the adoption of FD-hPL as a fully xenogeneic free alternative to FBS to support the use of SH-SY5Y cells as a neurodegeneration model.

PET quantification performance of the oversize-volume-of-interest approach in the context of tumour dosimetry in radionuclide therapy planning.

Objective.The partial-volume effect (PVE) is an important factor impairing tumour quantification in molecular imaging. The commonly used contour-volume-of-interest (contour-VOI) approach to correct for this effect employs phantom-based recovery coefficients. Applying oversize-VOIs could offer superior quantification accuracy in small lesions. The oversize-VOI approach uses a large oversize volume to determine the total tumour activity after applying a background correction. Aims of this study were to provide a procedure for the application of the oversize-VOI approach and to compare its performance to the contour-VOI approach in PET imaging.Approach.A sphere tumour model was simulated to determine the oversize diameter that contained 90%, 95%, and 98% of the total activity as a function of the tumour size. Experimental investigations involving phantom and clinical data were conducted on a digital PET/CT scanner. In the phantom investigation, 12 spherical tumour inserts (diameters ranging from 3.7 to 37.4 mm) containing18F-solution were used. The accuracy of the contour- and oversize-VOI approach was evaluated for different signal-to-background ratios (20-3). Clinically, both approaches were applied on PET/CT images acquired with18F-labelled prostate-specific membrane antigen in prostate cancer patients.Main results.From the tumour model, we deduced that an oversize-VOI of two PET spatial resolutions larger than the physical lesion diameter contains at least 98% of the total activity for lesions with diameters down to one PET spatial resolution, while minimizing the background contribution. Both approaches were robust against varying phantom and clinical imaging conditions. Performance of the oversize-VOI approach was favorable for lesions below 10 mm in diameter, whereas the contour-VOI approach was slightly more accurate for sizes above 10 mm.Significance.The oversize-VOI approach facilitates image quantification of small tumours. It is simple and effective to correct for the PVE and may be used in pre-therapeutic (small) tumour dosimetry.

In vitro antiproliferative effects of Vatairea macrocarpa (Benth.) Ducke lectin on human tumor cell lines and in vivo evaluation of its toxicity in Drosophila melanogaster.

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.

Cutting-edge collagen biocomposite reinforced with 2D nano-talc for bone tissue engineering.

The advancement of nanobiocomposites reinforced with 2D nano-materials plays a pivotal role in enhancing bone tissue engineering. In this study, we introduce a nanobiocomposite that reinforces bovine collagen with 2D nano-talc, a recently exfoliated nano-mineral. These nanobiocomposites were prepared by blending collagen with varying concentrations of 2D nano-talc, encompassing mono- and few-layers talc from soapstone nanomaterial. Extensive characterization techniques including AFM, XPS, nano-FTIR, s-SNOM nanoimaging, Force Spectroscopy, and PeakForce QNM® were employed. The incorporation of 2D nano-talc significantly enhanced the mechanical properties of the nanobiocomposites, resulting in increased stiffness compared to pristine collagen. In vitro studies supported the growth and proliferation of osteoblasts onto 2D nano-talc-reinforced nanobiocomposites, as well as showed the highest mineralization potential. These findings highlight the substantial potential of the developed nanobiocomposite as a scaffold material for bone tissue engineering applications.

Vertical heterostructure of graphite-MoS2 for gas sensing.

2D materials, given their form-factor, high surface-to-volume ratio, and chemical functionality have immense use in sensor design. Engineering 2D heterostructures can result in robust combinations of desirable properties but sensor design methodologies require careful considerations about material properties and orientation to maximize sensor response. This study introduces a sensor approach that combines the excellent electrical transport and transduction properties of graphite film with chemical reactivity derived from the edge sites of semiconducting molybdenum disulfide (MoS2) through a two-step chemical vapour deposition method. The resulting vertical heterostructure shows potential for high-performance hybrid chemiresistors for gas sensing. This architecture offers active sensing edge sites across the MoS2 flakes. We detail the growth of vertically oriented MoS2 over a nanoscale graphite film (NGF) cross-section, enhancing the adsorption of analytes such as NO2, NH3, and water vapor. Raman spectroscopy, density functional theory calculations and scanning probe methods elucidate the influence of chemical doping by distinguishing the role of MoS2 edge sites relative to the basal plane. High-resolution imaging techniques confirm the controlled growth of highly crystalline hybrid structures. The MoS2/NGF hybrid structure exhibits exceptional chemiresistive responses at both room and elevated temperatures compared to bare graphitic layers. Quantitative analysis reveals that the sensitivity of this hybrid sensor surpasses other 2D material hybrids, particularly in parts per billion concentrations.

Foreign body in the upper oesophagus - A double scope extraction approach.

Flexible esophagogastroduodenoscopy is the gold standard for removing FB of the upper gastrointestinal tract. However large sharped FB are usually challenging to remove and are the subtype that most often requires surgery. We describe a case of a patient with a dental prothesis impacted in the proximal oesophagus. After a failed conventional approach, we made a successful attempt with two regular scopes with two independent operators.

Near-infrared fluorescence lymph node template region dissection plus backup lymphadenectomy in open radical cystectomy for bladder cancer using an innovative handheld device: A single center experience.

BACKGROUND: The extent of pelvic lymphadenectomy (PLND) as part of radical cystectomy (RC) for bladder cancer (BC) remains unclear. Sentinel-based and lymphangiographic approaches could lead to reduced morbidity without sacrificing oncologic safety. OBJECTIVE: To evaluate the feasibility and diagnostic value of fluorescence-guided template sentinel region dissection (FTD) using a handheld near-infrared fluorescence (NIRF) camera in open radical cystectomy. DESIGN, SETTING, AND PARTICIPANTS: After peritumoral cystoscopic injection of indocyanine green (ICG) 21 patients underwent open RC with FTD due to BC between June 2019 and June 2021. Intraoperatively, the FIS-00 Hamamatsu Photonics® NIRF camera was used to identify and resect fluorescent template sentinel regions (FTRs) followed by extended pelvic lymphadenectomy (ePLND) as oncological back-up. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Descriptive analysis of positive and negative results per template region. RESULTS AND LIMITATIONS: FTRs were identified in all 21 cases. Median time (range) from ICG injection to fluorescence detection was 75 (55-125) minutes. On average (SD), 33.4 (9.6) lymph nodes were dissected per patient. Considering template regions as the basis of analysis, 67 (38.3%) of 175 resected regions were NIRF-positive, with 13 (7.4%) regions harboring lymph node metastases. We found no metastatic lymph nodes in NIRF-negative template regions. Outside the standard template, two NIRF-positive benign nodes were identified. CONCLUSION: The concept of NIRF-guided FTD proved for this group all lymph node metastases to be found in NIRF-positive template regions. Pending validation in a larger collective, resection of approximately 40% of standard regions may be sufficient and may result in less morbidity.

Safety and Efficacy of Para-Aminohippurate Coinfusion for Renal Protection During Peptide Receptor Radiotherapy in Patients with Neuroendocrine Tumors.

Para-aminohippurate, also known as p-aminohippuric acid (PAH), is used clinically to measure effective renal plasma flow. Preclinically, it was shown to reduce 177Lu-DOTATOC uptake in the kidneys while improving bioavailability compared with amino acid (AA) coinfusion. We report the safety and efficacy of PAH coinfusion during peptide receptor radiotherapy in patients with neuroendocrine tumors. Methods: Twelve patients with metastatic or unresectable gastroenteropancreatic neuroendocrine tumors received 177Lu-DOTATOC in 33 treatment cycles. Either 8 g of PAH or a mixture of 25 g of arginine and 25 g of lysine were coinfused. Safety was assessed by monitoring laboratory data, including hematologic and renal data, as well as electrolytes obtained before and 24 h after treatment. For radiation dosimetry, whole-body scans were performed at 1, 24, and 48 h and a SPECT/CT scan was performed at 48 h, along with blood sampling at 5 min and 0.5, 2, 4, 24, and 48 h after administration. Absorbed dose estimations for the kidneys and bone marrow were performed according to the MIRD concept. Results: In 15 treatment cycles, PAH was coinfused. No changes in mean creatinine level, glomerular filtration rate, and serum electrolytes were observed before or 24 h after treatment when using PAH protection (P ≥ 0.20), whereas serum chloride and serum phosphate increased significantly under AA (both P < 0.01). Kidney-absorbed dose coefficients were 0.60 ± 0.14 Gy/GBq with PAH and 0.53 ± 0.16 Gy/GBq with AA. Based on extrapolated cumulative kidney-absorbed doses for 4 cycles, 1 patient with PAH protection and 1 patient with AA protection in our patient group would exceed the 23-Gy conservative threshold. The bone marrow-absorbed dose coefficient was 0.012 ± 0.004 Gy/GBq with PAH and 0.012 ± 0.003 Gy/GBq with AA. Conclusion: PAH is a promising alternative to AA for renal protection during peptide receptor radiotherapy. Further research is required to systematically investigate the safety profile and radiation dosimetry at varying PAH plasma concentrations.

Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen.

Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found for levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower, whereas DFC induced only low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the growing concern that co-exposure to environmental toxicants and their non-additive interactions may be a confounding factor that should not be neglected in environmental and human health risk assessment.

Ionizable Lipid Nanoparticle-Mediated TRAIL mRNA Delivery in the Tumor Microenvironment to Inhibit Colon Cancer Progression.

Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention. Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1-7 (Ang(1-7)) to reduce vascular compression and deposition of extracellular matrix in mice. Results: Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1-7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization. Discussion: Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors.

Treatment Of Post-Operative Chylothorax: The Role Of Intranodal Lymphangiography And Thoracic Duct Disruption.

Thoracic duct embolization has been increasingly adopted as a first-line therapy of chylothorax and this procedure includes lipiodol lymphangiography, thoracic duct access and embolization. Lymphangiography itself has a therapeutic role, with volume-dependent success rates of 37%-97% and even a reported 100% success rate in outputs of < 500 mL/day. We present a clinical case of a 48-years-old man diagnosed with esophageal squamous cell carcinoma, who underwent esophagectomy and presented with post-operative high-output (> 1L/day) chylothorax; thoracic duct embolization was proposed. Even though thoracic duct access and embolization were not achieved due to technical and anatomical factors, lipiodol lymphangiography and possibly thoracic duct maceration (after several punctures/attempts) contributed to the clinical success of the procedure, and this chylothorax with output values superior to those reported in the literature resolved within three days. As such, the therapeutic role of intranodal lymphangiography and thoracic duct disruption should be taken into account.

Exploration of Toxins from a Marine Annelid: An Analysis of Phyllotoxins and Accompanying Bioactives.

Proteinaceous toxins are peptides or proteins that hold great biotechnological value, evidenced by their ecological role, whether as defense or predation mechanisms. Bioprospecting using bioinformatics and omics may render screening for novel bioactives more expeditious, especially considering the immense diversity of toxin-secreting marine organisms. Eulalia sp. (Annelida: Phyllodocidae), a toxin bearing marine annelid, was recently shown to secrete cysteine-rich protein (Crisp) toxins (hitherto referred to as 'phyllotoxins') that can immobilize its prey. By analyzing and validating transcriptomic data, we narrowed the list of isolated full coding sequences of transcripts of the most abundant toxins or accompanying bioactives secreted by the species (the phyllotoxin Crisp, hyaluronidase, serine protease, and peptidases M12A, M13, and M12B). Through homology matching with human proteins, the biotechnological potential of the marine annelid's toxins and related proteins was tentatively associated with coagulative and anti-inflammatory responses for the peptidases PepM12A, SePr, PepM12B, and PepM13, and with the neurotoxic activity of Crisp, and finally, hyaluronidase was inferred to bear properties of an permeabilizing agent. The in silico analysis succeeded by validation by PCR and Sanger sequencing enabled us to retrieve cDNAs can may be used for the heterologous expression of these toxins.

Apple Core Unveiled: Malignant Colonic Obstruction Revealing an Unknown Rectosigmoid Neoplasm With Foreign Body Impaction.

This case report highlights a rare clinical scenario of a 46-year-old male presenting with constipation and fecaloid vomiting due to an impacted chicken bone within an unidentified rectosigmoid neoplasm, leading to acute malignant colonic obstruction. Emergent exploratory laparotomy revealed an impacted chicken bone lodged in a previously unknown rectosigmoid tumor. An anatomopathological examination revealed a mucinous adenocarcinoma with clear margins and one pericolic metastatic lymph node. The postoperative period was uneventful, and the patient was proposed for adjuvant chemotherapy. The abrupt onset of symptoms allowed for an early diagnosis, emphasizing the unexpected association between foreign body impaction and incidental malignant obstruction. This case underscores the complexity of managing foreign body ingestion in the gastrointestinal tract and emphasizes the crucial role of diagnostic imaging in surgical planning. Furthermore, it draws attention to the potential occurrence of colorectal cancer in younger individuals, emphasizing the necessity for clinical vigilance and screening strategies beyond conventional age recommendations.

Biodistribution and radiation dosimetry of 124I-mIBG in adult patients with neural crest tumours and extrapolation to paediatric models.

AIM: Positron emission tomography (PET) using 124I-mIBG has been established for imaging and pretherapeutic dosimetry. Here, we report the first systematic analysis of the biodistribution and radiation dosimetry of 124I-mIBG in patients with neural crest tumours and project the results to paediatric patient models. METHODS: Adult patients with neural crest tumours who underwent sequential 124I-mIBG PET were included in this retrospective single-center analysis. PET data were acquired 4, 24, 48, and/or 120 h after administration of a mean of 43 MBq 124I-mIBG. Whole-body counting and blood sampling were performed at 2, 4, 24, 48 and 120 h after administration. Absorbed organ dose and effective dose coefficients were estimated in OLINDA/EXM 2.2 according to the MIRD formalism. Extrapolation to paediatric models was performed based on mass-fraction scaling of the organ-specific residence times. Biodistribution data for adults were also projected to 123I-mIBG and 131I-mIBG. RESULTS: Twenty-one patients (11 females, 10 males) were evaluated. For adults, the organs exposed to the highest dose per unit administered activity were urinary bladder (1.54 ± 0.40 mGy/MBq), salivary glands (0.77 ± 0.28 mGy/MBq) and liver (0.65 ± 0.22 mGy/MBq). Mean effective dose coefficient for adults was 0.25 ± 0.04 mSv/MBq (male: 0.24 ± 0.03 mSv/MBq, female: 0.26 ± 0.06 mSv/MBq), and increased gradually to 0.29, 0.44, 0.69, 1.21, and 2.94 mSv/MBq for the 15-, 10-, 5-, 1-years-old, and newborn paediatric reference patients. Projected mean effective dose coefficients for 123I-mIBG and 131I-mIBG for adults were 0.014 ± 0.002 mSv/MBq and 0.18 ± 0.04 mSv/MBq, respectively. CONCLUSION: PET-based derived radiation dosimetry data for 124I-mIBG from this study agreed well with historical projected data from ICRP 53. The effective dose coefficients presented here may aid in guidance for establishing weight-based activity administration protocols.

Fibroblast Activation Protein α-Directed Imaging and Therapy of Solitary Fibrous Tumor.

Fibroblast activation protein α (FAPα) is expressed at high levels in several types of tumors. Here, we report the expression pattern of FAPα in solitary fibrous tumor (SFT) and its potential use as a radiotheranostic target. Methods: We analyzed FAPα messenger RNA and protein expression in biopsy samples from SFT patients using immunohistochemistry and multiplexed immunofluorescence. Tracer uptake and detection efficacy were assessed in patients undergoing clinical 68Ga-FAPα inhibitor (FAPI)-46 PET,18F-FDG PET, and contrast-enhanced CT. 90Y-FAPI-46 radioligand therapy was offered to eligible patients with progressive SFT. Results: Among 813 patients and 126 tumor entities analyzed from the prospective observational MASTER program of the German Cancer Consortium, SFT (n = 34) had the highest median FAPα messenger RNA expression. Protein expression was confirmed in tumor biopsies from 29 of 38 SFT patients (76%) in an independent cohort. Most cases showed intermediate to high FAPα expression by immunohistochemistry (24/38 samples, 63%), which was located primarily on the tumor cell surface. Nineteen patients who underwent 68Ga-FAPI-46 PET imaging demonstrated significantly increased tumor uptake, with an SUVmax of 13.2 (interquartile range [IQR], 10.2), and an improved mean detection efficacy of 94.5% (SEM, 4.2%), as compared with 18F-FDG PET (SUVmax, 3.2 [IQR, 3.1]; detection efficacy, 77.3% [SEM, 5.5%]). Eleven patients received a total of 34 cycles (median, 3 cycles [IQR, 2 cycles]) of 90Y-FAPI-46 radioligand therapy, which resulted in disease control in 9 patients (82%). Median progression-free survival was 227 d (IQR, 220 d). Conclusion: FAPα is highly expressed by SFT and may serve as a target for imaging and therapy. Further studies are warranted to define the role of FAPα-directed theranostics in the care of SFT patients.