PET Imaging Research Articles

Optimisation of Animal Handing and Timing of 2-deoxy-2-[18F]fluoro-D-glucose PET Tumour Imaging in Mice.

In humans, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) tumour-to-background contrast continues to increase long after a typical uptake period of 45 - 60min. Similar studies have not been performed in mice and the static imaging time point for most studies is arbitrarily set at 30 - 60min post-injection of [18F]FDG. Ideally, static PET imaging should be performed after the initial period of rapid uptake but this period has not been defined in mice, with previous dynamic studies in mice being limited to 60min. This study aimed to define the kinetics of [18F]FDG biodistribution over periods of 3 - 4h in different murine tumour models, both subcutaneous and autochthonous, and to further refine fasting and warming protocols used prior to imaging. Dynamic [18F]FDG PET-CT scans lasting 3 or 4h were performed with C57BL/6J and Balb/c nude mice bearing subcutaneous EL4 murine T-cell lymphoma and Colo205 human colorectal tumours, respectively, and with transgenic Eμ-Myc lymphoma mice. Prior to [18F]FDG injection, four combinations of different animal handling conditions were used: warming for 1h at 31°C; maintenance at room temperature (20 - 24°C), fasting for 6 - 10h and a fed state. Tumour mean standardised uptake value (SUVmean) peaked at 147 ± 48min post injection in subcutaneous tumours and 74 ± 31min in autochthonous Eμ-Myc lymphomas. The tumour-to-blood ratio (TBR) peaked at 171 ± 57 and 83 ± 33min in subcutaneous and autochthonous Eμ-Myc tumours, respectively. Fasting increased tumour [18F]FDG uptake and suppressed myocardial uptake in EL4 tumour-bearing mice. There was a good correlation between tumour SUVmean and Ki calculated using an input function (IDIF) derived from the inferior vena cava. Delayed static [18F]FDG-PET imaging (> 60min) in both autochthonous and subcutaneous tumours in improved tumour-to-background contrast and increased reproducibility.

BIOM-37. EXPLORING L-TYPE AMINO ACID TRANSPORTER 1 (LAT1) AS A DIAGNOSTIC MARKER AND THERAPEUTIC TARGET IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS (MPNST)

Abstract OBJECTIVES Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that frequently arise from benign plexiform neurofibromas (PN). Approximately half of MPNST are associated with Neurofibromatosis type 1 (NF1). Despite partial elucidation of the molecular mechanisms underlying MPNST, diagnosis remains challenging, and prognosis is poor. Previously, we found that MPNST cells have elevated βIII-spectrin, a cytoskeletal protein involved in cell morphology and regulation of transporters, including L-type Amino Acid Transporter 1 (LAT1). LAT1 facilitates transport of large neutral amino acids and is upregulated in other cancer types. Our objective is to investigate LAT1 as a diagnostic marker and therapeutic target for MPNST. METHODS Gene and protein expression were determined by qPCR and WES protein analysis, respectively. The effect of shRNA knockdown of LAT1 in MPNST cells was assessed using IncuCyte proliferation assays as well as multiple mouse models. Tumor uptake of [18F] FDOPA, primarily transported by LAT1, in MPNST PDX tumors was assessed using PET/CT imaging. RESULTS LAT1 was expressed in MPNST (n=14) vs. benign PN tissues (n=6). Additionally, in human and murine MPNST cells, shRNA-mediated knockdown of LAT1 suppressed proliferation of MPNST cells in vitro and tumor growth in vivo. In a subcutaneous tumor growth model, intratumor injection of shLAT1 lentivirus reduced tumor volume to approximately 50% of control. Furthermore, uptake of [18F] FDOPA by LAT1 in MPNST PDX tumors was detected by PET/CT imaging. WU-356 PDX tissues exhibited higher LAT1 expression as well as increased uptake of [18F] FDOPA in tumors. Conversely, PET imaging showed significantly lower uptake of [18F] FDOPA in LAT1 knockdown tumors (p<0.05). CONCLUSIONS These results suggest that LAT1 promotes the growth and survival of MPNST cells. In addition, these findings demonstrate the potential use of LAT1 and the radiotracer [18F] FDOPA as a diagnostic biomarker in the management of MPNST.

NIMG-20. DWIBS FOR PRIMARY CANCER DETECTION IN INTRACRANIAL METASTASIS: TWO CASE REPORTS

Abstract INTRODUCTION Diffusion Weighted Whole Body Imaging with background body signal Suppression (DWIBS) is an imaging technique that encompasses comprehensive imaging of the entire body through diffusion-weighted imaging (DWI). In recent years, it has been increasingly utilized for investigating the etiology of fever or primary cancer. Here we present two cases of DWIBS for searching for primary cancer in patient with intracranial metastasis. CASE PRESENTATION Case1: A 60-year-old man presented with headache and diplopia and was admitted to our hospital. MRI revealed a tumor in the clivus exhibiting contrast enhancement. Endoscopic transsphenoidal surgery confirmed the diagnosis of squamous cell carcinoma. DWIBS demonstrated high intensity in a region similar to the esophagus seen on contrast-enhanced CT, leading to the diagnosis of brain metastasis from esophageal cancer. Case 2: A 50-year-old man presented with left facial paralysis and left hemiplegia and was admitted to our hospital. MRI revealed a tumor in the right middle frontal gyrus. Craniotomy confirmed the diagnosis of adenocarcinoma. Although the primary cancer remained unidentified upon initial examination, subsequent investigations revealed it originated from the lung. DWIBS showed high intensity in a region similar to the lung. DISCUSSION While FDG-PET is commonly utilized for cancer detection, its invasiveness and limitations prompt consideration of alternative modalities such as DWIBS. Recently there are some studies that have shown DWIBS to be superior to FDG PET in detecting esophageal and lung cancers. Thus, DWIBS may serve as a viable option for primary cancer screening in hospitals or communities where access to FDG PET is limited. CONCLUSION Its non-invasive nature makes DWIBS an appealing option for primary cancer detection, and further advancements are anticipated.

Increased individual workload for nuclear medicine physicians over the past years: 2008-2023 data from The Netherlands.

To investigate temporal trends in the individual workload of nuclear medicine physicians at a large tertiary care academic center between 2008 and 2023. This study analyzed the reporting workload of nuclear medicine physicians in a large tertiary care academic center in The Netherlands on 36 unique (randomly sampled) calendar days, for each year between 2008 and 2023. The average daily departmental workload (measured with relative value units) was calculated for each year between 2008 and 2023. The individual workload was calculated by dividing the average daily departmental workload in each year by the available full-time equivalent nuclear medicine physicians in each year. Mann-Kendall tests were used to assess for any temporal monotonic trends in individual workload and types of nuclear medicine procedures performed. Individual workload increased significantly between 2008 and 2023 (Mann-Kendall tau of 0.611, P = 0.001). Individual workload in 2023 was 86% higher than in 2008. The use of positron emission tomography (PET) increased significantly (Mann-Kendall tau of 0.912, P < 0.001) between 2008 and 2023. The use of diagnostic scintigraphy decreased significantly in the same period (Mann-Kendall tau of -0.817, P < 0.001). The use of DEXA also showed a significant decrease (Mann-Kendall tau of -0.467, P = 0.013), but this decrease was negligible on a relative scale. The number of therapeutic procedures (Mann-Kendall tau of -0.100, P = 0.626) remained statistically stable in this period. Our single-center study showed that the individual workload of nuclear medicine physicians has increased significantly between 2008 and 2023, driven by the rise in PET scans. The demand for both diagnostic and therapeutic nuclear medicine procedures and associated workload is expected to keep on increasing in the foreseeable future. This workload trend should be taken into account by policymakers involved in nuclear medicine staffing planning. A healthy balance between the nuclear medicine workforce and workload is necessary to maintain the quality of care, to be able to perform other important (academic) tasks such as research, educating and training medical students and residents, and management, and to prevent physician burnout and dropout.

Expert consensus on workflow of PET/CT with long axial field-of-view.

Positron emission tomography/computed tomography (PET/CT) imaging has been widely used in clinical practice. Long axial field-of-view (LAFOV) systems have enhanced clinical practice by leveraging their technological advantages and have emerged as the new state-of-the-art PET imaging modalities. A consensus was conducted to explore expert views in this emerging field to comprehensively elucidate the proposed workflow in LAFOV PET/CT examinations and highlight the potential challenges inherent in the workflow. A multidisciplinary task group formed by 28 experts from six countries over the world discussed and approved the consensus based on the published guidelines, peer-reviewed articles of LAFOV PET/CT, and the collective experience from clinical practice. This consensus focuses on the workflow that allows for a broader range of imaging protocols of LAFOV PET/CT, catering to diverse patient needs and in line with precision medicine principles. This consensus describes the workflows and imaging protocols of LAFOV PET/CT for various imaging scenarios including routine static imaging, dynamic imaging, low-activity imaging, fast imaging, prolonged imaging, delayed imaging, and dual-tracer imaging. In addition, imaging reconstruction and reviewing specific to LAFOV PET/CT imaging, as well as the main challenges facing installation and application of LAFOV PET/CT scanner were also summarized. This consensus summarized the various imaging workflow, imaging protocol, and challenges of LAFOV PET/CT imaging, aiming to enhance the clinical and research applications of these scanners.

Design, preclinical evaluation, and first-in-human PET study of [68Ga]Ga-PSFA-01: a PSMA/FAP heterobivalent tracer.

Prostate cancer (PCa), characterized by tumor heterogeneity, may exhibit low or absent prostate-specific membrane antigen (PSMA) expression in cancerous lesions, limiting the detection sensitivity of monospecific probes. Given that fibroblast activation protein (FAP) is frequently overexpressed in the tumor microenvironment (TME), we developed a PSMA/FAP dual-targeting tracer to address this limitation. The precursor (PSFA-01) was synthesized by coupling a quinolone-based FAP-targeting scaffold and EuK with HBED-CC via amide bonds. The dual-receptor-binding affinity and cell uptake of PSFA-01 and [natGa]Ga-PSFA-01 was evaluated in vitro. Micro-PET/CT imaging was performed on 22Rv1 and U87MG tumor-bearing mice. The feasibility of [68Ga]Ga-PSFA-01 PET/CT in a clinical setting was evaluated in a metastatic prostate cancer patient, and the results were compared with those of [68Ga]Ga-FAPI-04 and [68Ga]Ga-PSMA-11 PET/CT. PSFA-01 and [natGa]Ga-PSFA-01 showed high affinity for both FAP and PSMA proteins (Ki = 0.14-1.02 nM). On micro-PET/CT imaging, the 22Rv1 tumor uptake of [68Ga]Ga-PSFA-01 (SUVmax = 3.89 ± 0.47) was higher than that of [68Ga]Ga-PSMA-11 (SUVmax = 2.96 ± 0.48). The U87MG tumor uptake of [68Ga]Ga-PSFA-01 was significantly higher (SUVmax = 7.29 ± 1.13) than [68Ga]Ga-FAPI-04 (SUVmax = 0.28 ± 0.12), showing tumor to muscle ratio as 12.68 ± 1.93 at 1h p.i. On clinical trial, the primary tumor and metastatic lesions were distinctly identified by [68Ga]Ga-PSFA-01 (21 lesions), demonstrating superior performance compared to [68Ga]Ga-FAPI-04 (3 lesions) and [68Ga]Ga-PSMA-11 (13 lesions) in terms of lesion count and specificity. [68Ga]Ga-PSFA-01 exhibited satisfactory PSMA and FAP dual-receptor-targeting properties both in vitro and in vivo. This study highlights the clinical feasibility of [68Ga]Ga-PSFA-01 PET/CT for detecting metastatic tumors of prostate cancer more sensitively compared to monomeric [68Ga]Ga-PSMA-11 and [68Ga]Ga-FAPI-04, which also suggests that a PSMA/FAP dual-targeted radionuclide therapy could potentially overcome challenges related to tumor heterogeneity and insufficient PSMA expression in PCa. Clinical trial registry NCT06387381, Registered 1 May 2024.

2-[18F]F-p-aminobenzoic acid specifically detects infective endocarditis in positron emission tomography.

To the present day infective endocarditis (IE) represents a life-threatening disease with high mortality rate especially when caused by Staphylococcus aureus (S. aureus), the most common causative pathogen in this disease. Diagnosis of IE is based on clinical manifestations, pathogen detection by blood cultures and echocardiographic or other imaging findings. However, none of the methods used is capable of detecting the causative bacterial cells on the endothelium directly. Modern molecular imaging such as positron emission tomography/computed tomography (PET/CT) is playing an increasingly important role in unclear IE cases. This study focused on 2-[18F]F-p-aminobenzoic acid (2-[18F]F-PABA), a bacteria specific tracer for the diagnosis of IE using PET imaging for direct pathogen detection. In vitro assays were performed to analyze 2-[18F]F-PABA uptake by S. aureus. For proof-of-concept in vivo trials an endocarditis mouse model was used to diagnose IE by PET/Magnetic resonance (MR) imaging. A subcutaneous abscess mouse model was supplemented to create larger bacterial vegetations for PET imaging. 2-[18F]F-PABA in vitro uptake by S. aureus was confirmed. Only living bacteria were able to accumulate the tracer while the extent of uptake varied between different S. aureus strains. In the in vivo proof-of-concept, IE was visualized in mice using 2-[18F]F-PABA-PET/MR imaging. Subsequently, 2-[18F]F-PABA specifically located S. aureus vegetations in the subcutaneous abscess model. This study highlights the great potential of 2-[18F]F-PABA imaging for the direct detection of IE. Future studies might further investigate the clinical potential of this molecular imaging approach, finally aiming at a clinical implementation.

Emerging Radiopharmaceuticals in Pet Imaging for Mesothelioma: A Review of [18F]FDG Alternatives.

Mesothelioma is a malignant tumor associated primarily with asbestos exposure, characterized by an aggressive nature and poor prognosis. Accurate diagnosis, staging, and monitoring of therapeutic response are crucial for effective patient management. Along with a computed tomography (CT) scan, fluorodeoxyglucose labeled with fluorine-18 ([18F]FDG) positron emission tomography (PET) is commonly used in mesothelioma evaluation. However, it has some limitations, including lower sensitivity after pleurodesis and poor accuracy for involved lymph node evaluation. Thus, there is the need to explore other agents. The aim of the present review is to analyze the current literature on the use of alternative radiopharmaceuticals for PET imaging in patients with mesothelioma. A comprehensive search of scientific databases (PubMed, Scopus, and Web of Science) for studies published in the last decade was performed by using the following keywords: "mesothelioma" AND "PET" AND "PET/CT" "radiopharmaceuticals", "[18F]FDG alternatives". Articles focused solely on [18F]FDG, non-English publications or preclinical studies, reviews, meeting abstracts, letters to the editors, and editorials were excluded. A qualitative assessment was made by using the Critical Appraisal Skills Programme (CASP) checklist for diagnostic test studies, when applicable. In total, 14 papers were selected; in seven articles more than five patients were enrolled, while the other seven were only clinical cases (enrolling up to two subjects). [18F]/gallium-68 ([68Ga])-labeled fibroblast activation protein inhibitor (FAPI) compounds, [18F]Fluorothymidine ([18F]FLT), methionine labeled with carbon-11 ([11C]MET), and fluoromisonidazole labeled with fluorine-18 ([18F]FMISO) PET/CT were the alternative agents used most often. In 12 articles, [18F]FDG PET/CT was used as a comparator imaging modality. Detection rate of [18F]FDG was similar to the other radiopharmaceuticals ([68Ga]/[18F]-labeled FAPI compounds, [18F]FLT, [18F]FMISO, [11C]MET, and [68Ga]-Pentaxifor), although radiolabeled FAPI seems to exhibit a higher diagnostic performance. [18F]FDG is still a valuable agent in patients with mesothelioma. However, radiolabeled FAPI appears to be promising and its theranostic properties should therefore be further assessed.

Machine Learning Models Based on [18F]FDG PET Radiomics for Bone Marrow Assessment in Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma is a heterogeneous group of cancers that triggers bone marrow infiltration in 20–40% of cases. Bone marrow biopsy in combination with a visual assessment of [18F]FDG PET/CT images is used to assess the marrow status. Despite the potential of both techniques, they still have limitations due to the subjectivity of visual assessment. The present study aims to develop models based on bone marrow uptake in [18F]FDG PET/CT images at the time of diagnosis to differentiate bone marrow status. For this purpose, a model trained for skeleton segmentation and based on the U-Net architecture is retrained for bone marrow segmentation from CT images. The mask obtained from this segmentation together with the [18F]FDG PET image is used to extract radiomics features with which 11 machine learning models for marrow status differentiation are trained. The segmentation model yields very satisfactory results with Jaccard and Dice index values of 0.933 and 0.964, respectively. As for the classification models, a maximum F1_score_weighted and F1_score_macro of 0.962 and 0.747, respectively, are achieved. This highlights the potential of these features for bone marrow assessment, laying the foundation for a new clinical decision support system.

Highlights of the 2024 ASCO Annual Meeting: radiotherapy of head and neck cancer

At the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO), several important studies on radiotherapy for head and neck squamous cell carcinoma (HNSCC) were presented. There were two Chinese phaseIII trials on treatment escalation for locally advanced nasopharyngeal carcinoma: adjuvant immune checkpoint inhibition with camrelizumab after induction chemotherapy and cisplatin-based chemoradiotherapy (RCT) in the DIPPER trial reached the primary endpoint of improved event-free survival (EFS) but did not improve overall survival (OS). Simultaneous and adjuvant administration of the angiogenesis inhibitor endostar in addition to cisplatin-based RCT for locally advanced nasopharyngeal carcinoma led to asignificant improvement in progression-free survival (PFS) and OS. Another major focus was on treatment optimization and deintensification for oropharyngeal cancer (OPC): using intensity-modulated proton therapy (IMPT), aphaseIII trial demonstrated noninferiority in definitive RCT for OPC compared to photon-based intensity-modulated radiotherapy (IMRT). In adjuvant treatment of human papillomavirus-positive (HPV+) OPC, the long-term results of the E3311 phaseII study confirmed that individually deintensified radiotherapy is feasible. Lee etal. showed with the results of aphaseII study that HPV+ OPC might be treatable with chemoradiotherapy to atotal dose of only 30 Gy if no hypoxia is detected in the 18F‑fluoromisonidazole positron-emission tomography-computed tomography (F-MISO-PET) scan. Both the deintensified treatment of HPV+ OPC as well as additive immune checkpoint and angiogenesis inhibition in chemoradiotherapy of nasopharyngeal carcinoma require further studies before they can be recommended in clinical practice.

Recurrence Detection by Hybrid [18F]FDG-PET in Advanced Head and Neck Squamous Cell Carcinoma.

In the clinical management of advanced stage head and neck squamous cell carcinoma, the use of hybrid [18F]FDG-PET imaging is well established. However, there is ongoing debate regarding the optimal frequency of hybrid PET scans to be included in follow-up protocols, particularly if the initial post-therapeutic scan is negative. We conducted a single-center 10-year retrospective study involving all patients who underwent hybrid PET scans for the follow-up of advanced stage head and neck cancer. A total of 285 patients were included. Out of 199 patients with a negative 3-month hybrid PET, 15% subsequently developed a recurrence during further follow-up. Notably, 90% of these recurrences were detected by hybrid PET. Fifteen percent of patients with a negative 3-month hybrid PET experienced a recurrence. Given that the majority of recurrences were detected by hybrid PET scans, there is a compelling argument for incorporating regular repetitive scans during follow-up.

Evaluation of a Novel MET-Targeting Camelid-Derived Antibody in Head and Neck Cancer.

In head and neck squamous cell carcinoma (HNSCC), the mesenchymal epithelial transition (MET) receptor drives cancer growth, proliferation, and metastasis. MET is known to be overexpressed in HNSCC and, therefore, is an appealing therapeutic target. In this study, we evaluated MET expression in patients with HNSCC and investigated the potential imaging application of a novel MET-binding single-domain camelid antibody using positron emission tomography/computed tomography (PET/CT) in a preclinical MET-expressing HNSCC model. Multiplex immunostaining for MET protein performed on a tissue microarray from 203 patients with HNSCC found 86% of patients to have MET expression, with 14% having high expression and 53% having low MET expression. Using The Cancer Genome Atlas (TCGA) database, high MET RNA expression was associated with worse progression-free survival and overall survival in patients with HPV-negative HSNCC. Utilizing flow cytometry and immunofluorescence, our novel camelid antibody fused to a human IgG Fc chain (1E7-Fc) showed high binding affinity and specificity to high MET-expressing Detroit 562 cells but not to low MET-expressing HNSCC cells. The efficacy and biodistribution of [89Zr]Zr-1E7-Fc as a PET imaging agent was then investigated in a MET-expressing head and neck xenograft model. [89Zr]Zr-1E7-Fc rapidly localized and showed high tumor uptake in Detroit 562 xenografts (8.4% ID/g at 72 h postinjection), with rapid clearance from the circulatory system (2.7 tumor-to-blood radioactivity ratio at 72 h postinjection). Our preclinical data suggest that the camelid antibody 1E7-Fc could be a potential theranostic agent for HNSCC. Further investigations are warranted to confirm these findings in patients and to evaluate 1E7-Fc as an imaging agent and platform to deliver radionuclide or drug therapy to MET-driven cancers.

Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state.

A novel radiotracer, [11C]SL25.1188, targets monoamine oxidase-B (MAO-B) enzyme, found primarily in astrocytes, which metabolizes monoamines (including dopamine), particularly in subcortical regions. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. We aimed to test whether levels of MAO-B, an index of astrocyte function are low in the living brains of early psychosis and their high-risk states. Thirty-eight participants including antipsychotic-free/minimally exposed clinical participants with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-min positron emission tomography (PET) scan with [11C]SL25.1188, to measure MAO-B VT, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B VT (F(2,37.42) = 4.56, p = 0.02, Cohen's f = 0.49), controlling for tobacco (F (1,37.42) = 5.37, p = 0.03) and cannabis use (F(1,37.42) = 5.11, p = 0.03) with significantly lower MAO-B VT in CHR compared to HV (Cohen's d = 0.99). We report a significant cannabis effect on MAO-B VT (F(1,39.19) = 12.57, p = 0.001, Cohen's f = 0.57), with a significant group-by-cannabis interaction (F(2,37.30) = 3.82, p = 0.03, Cohen's f = 0.45), indicating lower MAO-B VT in cannabis-using clinical groups. Lower MAO-B VT levels were more robust in striatal than cortical regions, in both clinical groups (F(12,46.84) = 2.08, p = 0.04, Cohen's f = 0.73) and in cannabis users (F(6,46.84) = 6.42, p < 0.001, Cohen's f = 0.91). Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.

Long-term follow-up of bulky classic Hodgkin lymphoma managed with ABVD and PET-guided RT demonstrates excellent outcomes in PET-negative cases.

The outcome of 221 patients with bulky (≥10 cm) classic Hodgkin lymphoma (cHL) treated with doxorubicin, bleomycin, vinblastine, dacarbazine and consolidative radiotherapy (RT) only in those with a positive end-of-treatment (EOT) positron emission tomography (PET) scan was evaluated. With a median follow-up of 9.6 years, 5- and 10-year progression-free survival (PFS) in EOT PET-negative cases were 94.0% and 90.4%, respectively, and in PET-positive cases, 5/10-year PFS was 64.6% (p < 0.001), with 15% overall receiving RT. Five-year PFS for Deauville (D) score DX/D1-3 was 93.6%, compared with D4 66.7% (p < 0.001) and D5 33.3% (p < 0.001). Omission of RT in EOT PET-negative cases is associated with excellent long-term outcomes in bulky cHL.

PIPET: A Pipeline to Generate PET Phantom Datasets for Reconstruction Based on Convolutional Neural Network Training

There has been a strong interest in using neural networks to solve several tasks in PET medical imaging. One of the main problems faced when using neural networks is the quality, quantity, and availability of data to train the algorithms. In order to address this issue, we have developed a pipeline that enables the generation of voxelized synthetic PET phantoms, simulates the acquisition of a PET scan, and reconstructs the image from the simulated data. In order to achieve these results, several pieces of software are used in the different steps of the pipeline. This pipeline solves the problem of generating diverse PET datasets and images of high quality for different types of phantoms and configurations. The data obtained from this pipeline can be used to train convolutional neural networks for PET reconstruction.

The value of a PET scan in selecting the best lymph node to biopsy, and confirming the diagnosis of idiopathic multicentric Castleman disease with HLH and EBV viremia in a previously healthy adult

Introduction: Castleman disease (CD) is a rare lymphoproliferative disorder having a variegated clinical presentation. Diagnosis of the idiopathic HIV- and HHV8-negative multicentric CD (iMCD) subtype poses a challenge given its non-specific clinical manifestations. iMCD presents as diffuse lymphadenopathy with inflammatory manifestations, primarily driven by interleukin-6 (IL-6). Treatment includes suppressing the inflammation by targeting IL-6 with monoclonal antibodies such as siltuximab and, in severe cases, immuno-chemotherapy to control B- and plasma-cell activation. Case description: A previously healthy 43-year-old male presented to the emergency department with fever, night sweats, anasarca, anaemia, thrombocytopenia and acute renal insufficiency. Extensive blood and imaging workup was initiated. Several diagnoses were entertained including viral infections (comprising COVID-19), haemophagocytic lymphohistiocytosis, lymphoma and autoimmune conditions. Initial axillary lymph node biopsy was not diagnostics. A positron emission tomography (PET) scan showed diffuse and symmetrical cervical and hilar/mediastinal lymphadenopathies. A mediastinal lymph node biopsy was then performed and indicated iMCD. The patient was treated with high-dose steroids and siltuximab. An Epstein-Barr virus (EBV) PCR was positive, and rituximab was added to the treatment. The patient recovered and felt well after two months. Conclusions: Non-specific symptoms, non-diagnostic first biopsy and iMCD resemblance to haemophagocytic lymphohistiocytosis further complicated the diagnosis. A PET scan allowed the best selection of a lymph node to be biopsied. Anti-IL6 is the recommended treatment; however, we are lacking information on the duration of siltuximab, and the long-term toxicity and immunosuppressive effect of this treatment. The contribution of EBV reactivation in the development and treatment of iMCD needs further investigation.

Feasibility of Early 68Ga-FAP-2286 PET Imaging: A Case Study.

Fibroblast activation protein (FAP) has emerged as a promising molecular target for diagnostic and therapeutic strategies. Previous research, including our own study and other published reports, has highlighted the potential of FAP inhibitors labeled with 68Ga as effective diagnostic radiopharmaceuticals. In this study, we present a comparative analysis of early and late PET/CT scans, using 68Ga-FAP-2286, for the detection of tumor lesions in a patient with metastatic breast adenocarcinoma.

An automated pheochromocytoma and paraganglioma lesion segmentation AI-model at whole-body 68Ga- DOTATATE PET/CT.

Somatostatin receptor (SSR) targeting radiotracer 68Ga-DOTATATE is used for Positron Emission Tomography (PET)/Computed Tomography (CT) imaging to assess patients with Pheochromocytoma and paraganglioma (PPGL), rare types of Neuroendocrine tumor (NET) which can metastasize thereby becoming difficult to quantify. The goal of this study is to develop an artificial intelligence (AI) model for automated lesion segmentation on whole-body 3D DOTATATE-PET/CT and to automate the tumor burden calculation. 132 68Ga-DOTATATE PET/CT scans from 38 patients with metastatic and inoperable PPGL, were split into 70, and 62 scans, from 20, and 18 patients for training, and test sets, respectively. The training set was further divided into patient-stratified 5 folds for cross-validation. 3D-full resolution nnUNet configuration was trained with 5-fold cross-validation. The model's detection performance was evaluated at both scan and lesion levels for the PPGL test set and two other clinical cohorts with NET (n = 9) and olfactory neuroblastoma (ONB, n = 5). Additionally, quantitative statistical analysis of PET parameters including SUVmax, total lesion uptake (TLU), and total tumor volume (TTV), was conducted. The nnUNet AI model achieved an average 5-fold validation dice similarity coefficient of 0.84 at the scan level. The model achieved dice similarity coefficients (DSC) of 0.88, 0.6, and 0.67 at the scan level, the sensitivity of 86%, 61.13%, and 61.64%, and a positive predictive value of 89%, 74%, and 86.54% at the lesion level for the PPGL test, NET and ONB cohorts, respectively. For PPGL cohorts, smaller lesions with low uptake were missed by the AI model (p < 0.001). Anatomical region-based failure analysis showed most of the false negative and false positive lesions within the liver for all the cohorts, mainly due to the high physiologic liver background activity and image noise on 68Ga- DOTATATE PET scans. The developed deep learning-based AI model showed reliable performance for automated segmentation of metastatic PPGL lesions on whole-body 68Ga-DOTATATE-PET/CT images, which may be beneficial for tumor burden estimation for objective evaluation during therapy follow-up. https://www. gov/study/NCT03206060 , https://www. gov/study/NCT04086485 , https://www. gov/study/NCT05012098 .

Possibilities of radiological methods of diagnosis of metastatic castration-resistant prostate cancer (Review Article).

Abstract Metastatic castration-resistant prostate cancer (mCRPC) is characterized by the progression of the tumor process when it becomes unresponsive to androgen-deprivation therapy. The incidence of bone metastases in these patients reaches up to 90%. Imaging modalities play a pivotal role in the diagnosis of this oncological condition. Computed tomography (CT) and magnetic resonance imaging (MRI) offer advantages in anatomical visualization; however, they face limitations in assessing the efficacy of prostate cancer treatment. Scintigraphy is applicable in screening for skeletal bone metastatic involvement but has limitations in assessing disease progression. Positron emission tomography combined with computed tomography (PET/CT) and single-photon emission computed tomography (SPECT/CT) are utilized for early detection of local or systemic spread of prostate cancer. The assessment of quantitative data on radiopharmaceutical uptake using PSMA PET imaging is used for predicting the efficacy of antitumor therapy. With the introduction of the radiopharmaceutical 177Lu-PSMA into clinical practice, the perspective of conducting radionuclide therapy with simultaneous efficacy evaluation through hybrid imaging methods has emerged. The capabilities of imaging modalities in assessing bone metastases present a particular interest for research and systematization of the data obtained to develop optimal parameters for conducting radioligand therapy and evaluating its efficacy. Aims: To explore the capabilities of imaging modalities in diagnosing metastatic castration-resistant prostate cancer. Conclusions: The analyzed literature data indicate that imaging methods for diagnosing mCRPC vary in sensitivity and specificity, have their advantages and disadvantages, which underscores the necessity for a comprehensive approach in their utilization. The development and advancement of methods for quantitative assessment of treatment efficacy, identification of prognostic markers can influence a more informed choice of treatment tactics and radiopharmaceutical selection, potentially leading to an increase in overall survival.

Completely non-invasive prediction of IDH mutation status based on preoperative native CT images.

The isocitrate dehydrogenase (IDH) mutation status is one of the most important markers according to the 2021 WHO classification of CNS tumors. Preoperatively, this information is usually obtained based on invasive biopsies, contrast-enhanced MR images or PET images generated using radioactive tracers. However, the completely non-invasive determination of IDH mutation status using routinely acquired preoperative native CT images has hardly been investigated to date. In our study, we show that radiomics-based machine learning allows to determine IDH mutation status based on preoperative native CT images both with very high accuracy and completely non-invasively. Based on independent test data, we are able to correctly identify 91.1% of cases with an IDH mutation. Our final model, containing only six features, exhibits a high area under the curve of 0.847 and an excellent area under the precision-recall curve of 0.945. In the future, such models may be used for a completely non-invasive prediction of important genetic markers, potentially allowing treating physicians to reduce the number of biopsies and speed up further treatment planning.