Idiopathic retroperitoneal fibrosis (IRF) is a rare fibro-inflammatory disease that is often diagnosed only after the development of complications, making early recognition and long-term management challenging. 18F-FDG PET/CT provides both anatomical and functional information, enabling accurate assessment of disease extent and monitoring of treatment response in patients with IRF. We report a 64-year-old man who presented with abdominal pain and difficulty defecating for 8 months. Laboratory tests showed elevated inflammatory markers, whereas tumor markers and immunological parameters were within normal limits. 18F-FDG PET/CT revealed a hypermetabolic soft-tissue mass with predominant presacral involvement. The lesion encased the bilateral internal and external iliac arteries and pelvic ureters, with limited cranial extension to the distal common iliac arteries, resulting in bilateral hydroureteronephrosis. Histopathological examination confirmed IRF. Following glucocorticoid therapy, follow-up 18F-FDG PET/CT demonstrated a marked reduction in lesion size and metabolic activity, indicating a favorable treatment response. This case represents one of the few reported cases of IRF with predominant presacral involvement evaluated with serial 18F-FDG PET/CT. The findings highlight the value of 18F-FDG PET/CT in assessing disease activity, supporting differential diagnosis, and monitoring response to corticosteroid therapy in atypical presentations of IRF.
To evaluate the relative contribution of the 400 Gy perfused liver absorbed dose (PLAD) threshold and tumor size in predicting complete response (CR) after yttrium-90 (Y-90) radiation segmentectomy (RS) in hepatocellular carcinoma (HCC), and to investigate the prognostic discrimination of a modified Barcelona Clinic Liver Cancer (BCLC) classification based on a 3 cm cutoff in solitary lesions compared with the standard BCLC 2026 staging system. Fifty-five patients (67 target lesions) who underwent RS with Y-90 glass microspheres between June 2022 and June 2025, met BCLC 2026 stage A/B criteria, and had a target lesion diameter ≤ 8 cm were retrospectively analyzed. Patients with solitary lesions included within standard BCLC-A were reclassified according to tumor diameter: those with lesions ≤ 3 cm as modified stage A, and those with lesions > 3 cm—together with existing multinodular BCLC-B cases—as modified stage B. The primary endpoint was CR at 6 months according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall mRECIST response at the patient level and localized mRECIST response at the lesion level were evaluated. Predictors of CR were assessed by univariate and multivariate logistic regression. The mean age was 65 ± 7.8 years, and 72.7
Abstract Background Radioactively labeled somatostatin analogs (SSAs) are used in PET imaging of meningiomas due to the high expression of somatostatin receptor (SSTR) subtype 2. 18 F-labeled SSTR-tracers offer several economic and logistical advantages over 68 Ga-labeled tracers, such as a cyclotron-based production, higher activities per synthesis, a lower positron energy resulting in improved spatial resolution, and a longer half-life. Owing to the advantages over the most commonly used 68 Ga-labeled SSAs, [ 18 F]SiTATE - although not yet approved by FDA or EMA - is currently in clinical use. The study compares [ 18 F]SiTATE PET uptake with histological SSTR2-expression in meningiomas. Results A correlation of SUV values and immunohistochemical SSTR2-expression was performed in 12 patients (42% female, mean age 68.8 ± 7.2 years). This study demonstrates a strong and significant correlation between [ 18 F]SiTATE uptake (SUV mean ) and histological SSTR2-immune-reactivity-score (SSTR2-IRS) values ( r = 0.80; p = 0.002). In addition, a significant difference in [ 18 F]SiTATE uptake (SUV mean ) was observed between low SSTR-expressing lesions (scores 0–1) and high SSTR-expressing lesions (scores 2–3; p = 0.006). Furthermore, it was noted that in four cases, the molecular tumor volume (MTV) was underestimated using a threshold value of SUV min 4, presumably caused by a low SUV max , while the application of a 50% isocontour threshold led to an underestimation of the MTV in two lesions that showed high SUV max values. Conclusions [ 18 F]SiTATE PET shows a strong and significant correlation with SSTR2-expression in meningiomas. However, neither of the two threshold methods yielded MTVs comparable to MRI volumes in all cases. Further studies are necessary to identify the conditions under which each threshold value yields the best MTV.
[18 F]fluorocholine PET/CT is increasingly used for localization of hyperfunctioning parathyroid tissue, but its real-world positioning after non-conclusive conventional imaging remains less clearly defined. This retrospective, observational, two-center study evaluated the use of [18 F]fluorocholine PET/CT as a second-level imaging modality in consecutive patients with suspected or biochemically confirmed primary hyperparathyroidism, within the Italian national reimbursement framework under Law 648/96. A total of 599 consecutive patients evaluated between February 2022 and July 2025 were included. [99 m]Tc-sestamibi imaging, with or without SPECT/CT, was positive/localizing in 270/599 patients (45.1
Inflammation plays a central role in the initiation, progression, and destabilization of atherosclerotic plaques. Persistent vascular inflammation despite therapeutic intervention may contribute substantially to residual cardiovascular risk. In this context, [18F]fluorodeoxyglucose-positron-emission-tomography ([18F]FDG PET) imaging has emerged as a non-invasive imaging biomarker capable of visualizing and quantifying vascular inflammatory activity in vivo. Previously published studies showed that the use of [18F]FDG PET may provide a non-invasive assessment of arterial inflammation. Accordingly, we aimed to systematically summarize treatment studies using [18F]FDG PET as an endpoint marker. 18 studies were considered to be eligible for data extraction. Of these 22 articles, 10 investigated vascular inflammation reduction after trials with lipid-lowering therapies, the other 12 were considering the effect of novel anti-inflammatory drugs on vascular inflammation. This review provides an overview of the additional value that [18F]FDG PET can provide as an endpoint marker in clinical intervention trials. Overall, statin therapies demonstrated a more consistent reduction in vascular [18F]FDG uptake compared to novel anti-inflammatory therapies.
Chimeric Antigen Receptor (CAR) T cell therapies for solid tumours face challenges regarding inefficient trafficking to the tumour site, limited extravasation and impaired persistence within an immunosuppressive microenvironment. Non-invasive imaging approaches capable of capturing the dynamic behaviour and biodistribution of CAR T cells are therefore needed to better understand these barriers. This study explores the use of compartmental modelling to interpret technetium-99 m pertechnetate ([99mTc]TcO4−) uptake by CAR T cells co-expressing the sodium iodide symporter (NIS) reporter gene in a prostate cancer NSG mouse model using single-photon emission computed tomography computerised tomography (SPECT/CT). Co-expression of hNIS with a prostate-specific membrane antigen (PSMA) targeting CAR did not impair CAR T cell function and enabled non-invasive visualisation of CAR-hNIS T cell infiltration in vivo. Dynamic SPECT/CT imaging revealed clear differences in tumour uptake between CAR-hNIS treated mice and control groups. Compartmental modelling using a reversible two-compartment framework demonstrated increased tracer influx and reduced tracer efflux in CAR-hNIS treated tumours. These kinetic changes indicate that tumour signal arises from NIS-mediated tracer uptake and delayed tracer washout in tumours containing infiltrating CAR T cells, rather than from passive perfusion or non-specific delivery alone. Immunohistochemistry confirmed CAR T cell infiltration in the tumours. This work establishes a proof-of-concept for applying kinetic modelling to interpret CAR T cell infiltration in vivo using dynamic hNIS-based SPECT imaging. By distinguishing tracer delivery from tracer washout kinetics and correcting for variability in tracer bioavailability, this approach provides a more sophisticated biological interpretation of tumour uptake than static imaging alone. These findings highlight the potential of integrating kinetic modelling into future quantitative cell-tracking strategies to improve the evaluation and optimisation of CAR T cell therapies for solid tumours.
The PROMISE framework standardizes PSMA PET interpretation using reference organs, particularly the liver. For hepatobiliary-excreted tracers (e.g., 18F-PSMA-1007), the spleen was proposed as an alternative reference, though without quantitative validation. We evaluated PSMA-ligand uptake patterns among 18F-PSMA-1007, 68Ga-PSMA-11, and 18F-DCFPyL to assess the validity of spleen-based referencing and develop a simple approach that may harmonize 18F-PSMA-1007 liver uptake with that of renally-excreted tracers. 331 consecutive PSMA PET-CT studies (n = 118/95/118 for 68Ga-PSMA-11/18F-PSMA-1007/18F-DCFPyL) were analyzed: SUVs were retrospectively measured in all studies in reference tissues (blood pool, liver, parotid), with SUVspleen also recorded for 18F-PSMA-1007. SUVliver differed markedly across tracers: 18F-PSMA-1007 (13.95 ± 4.71) > 68Ga-PSMA-11 (7.45 ± 4.59) ≈ 18F-DCFPyL (8.11 ± 1.78), p < 0.01. The elevated 18F-PSMA-1007 liver uptake expanded the PROMISE score-1 range (SUV range between SUVblood pool and SUVliver) and compressed that of score-2 (SUV range between SUVliver and SUVparotid). SUVspleen in this group (12.24 ± 5.67) showed only moderate correlation with SUVliver (r = 0.43) and exceeded SUVliver in 29
The signal regulatory protein alpha (SIRPα) receptor on myeloid cells binds cluster of differentiation (CD) antigen CD47 on tumor cells, resulting in a “don’t eat me” signal that inhibits phagocytosis. BI 765063, an anti-SIRPα antibody, may restore anti-tumor immunity by blocking this interaction. This phase I study aimed to assess target engagement and blockade of BI 765063 using quantitative 89Zr-immuno-PET, incorporating a previously developed correction method for non-target-mediated antibody catabolism. For this, four patients with advanced cancer received two cycles of [89Zr]Zr-BI 765063 and underwent three PET-scans per cycle up to 120 h post injection. The first cycle included a low dose of BI 765063 and the second a dose more than 20 times higher, intended to block the target. Directly after BI 765063 administration at the second cycle, ezabenlimab was administered to start the investigational treatment of the patients (BI 765063 + ezabenlimab, both every 3 weeks). Tumor uptake was corrected for antibody catabolism using literature-based reference values and normalized to plasma activity to calculate corrected tissue-to-plasma ratios (cTPR). Patlak analysis with the cTPR values yielded corrected net irreversible uptake rates (cKi). PET data were compared with RNA-sequencing data and macrophage marker immunohistochemistry. All ten tumor lesions showed target engagement by cTPR values at 120 h exceeding reference values. Positive cKi values were observed in all but one lesion, in which no Patlak analysis could be performed. cTPR values were lower for the blocking dose than the low dose, with five out of ten lesions within the range of non-target-mediated uptake, indicating partial target blockade. Target engagement observed by PET was supported by positive SIRPα mRNA expression and myeloid cell presence. Target engagement and blockade of BI 765063 were observed across all tumors, highlighting the potential of non-target-mediated antibody catabolism correction through cTPRs to improve quantification of target specific uptake with immuno-PET. ClinicalTrials.gov ID NCT05068102, Registered at 23 September 2021, https//clinicaltrials.gov/study/NCT05068102?term=NCT05068102. rank=1. Question: Does the anti-SIRPα antibody BI 765063 exhibit target-mediated uptake using quantitative ⁸⁹Zr-immuno-PET with correction for antibody catabolism? Pertinent findings: In this clinical PET study, patients with solid tumors underwent multiple PET scans after both a low antibody dose and a more than 20 times higher blocking dose of [⁸⁹Zr]Zr-BI 765063. Tissue to plasma ratios support target engagement across all evaluated tumor lesions, as well as target blockade following the blocking dose administration of BI 765063. Implications for patient care: Evidence of target engagement and blockade supports the clinical potential of anti-SIRPα antibodies to restore myeloid cell phagocytic function and downstream adaptive immunity, thereby informing dose optimization and potentially improving patient outcomes.
Bone metastases frequently occur in advanced-stage malignancies, contributing to diminished quality of life and unfavorable prognoses. However, conventional imaging modalities for diagnosing bone metastases exhibit inherent limitations. This study aimed to evaluate the diagnostic utility of fibroblast activation protein inhibitor (FAPI) imaging using [99mTc]Tc-H7ND for detecting bone metastases (BM). From June 2021 to September 2023, 564 patients with malignancies underwent FAPI imaging were screened. Eighty patients with confirmed or suspected BM were included. FAPI SPECT/CT was compared with CT, MRI, bone scintigraphy (BS), and [¹⁸F]FDG PET/CT for diagnostic efficacy. The uptake values in different components of BM were assessed, alongside discussions on potential of FAPI imaging in evaluating treatment response. Eighty patients (median age: 60 years; range: 23–79 years; 48 men) with confirmed or suspected BM were included, of these, 64 were confirmed BM. FAPI SPECT/CT demonstrated superior sensitivity (96.5
Postoperative staging and residual/metastatic lesion detection of papillary thyroid cancer (PTC) before radioiodine (RAI) ablation remains a critical clinical demand, especially for patients with intermediate to high-risk pathological features. Although 2-[18F] fluoro-2-deoxy-D-glucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) is widely applied in thyroid cancer imaging, its diagnostic sensitivity is suboptimal for small-volume, low-metabolic metastatic or residual lesions. Fibroblast activation protein (FAP), specifically overexpressed in tumor stromal cancer-associated fibroblasts (CAFs), has become a novel and reliable imaging target for oncological detection. This study aimed to head-to-head compare the diagnostic efficacy of [18F]AL-NOTA-FAPI-46 ([18F] FAPI-46) and [¹⁸F] FDG PET/CT in identifying postoperative residual and lymph node metastatic lesions in PTC patients prior to adjuvant ¹³¹I therapy. A total of 18 consecutive postoperative PTC patients scheduled for ¹³¹I ablation were prospectively enrolled. All patients underwent paired [18F] FAPI-46 and [18F] FDG PET/CT within a 1-week interval before treatment. A composite reference standard integrating histopathological results, standardized imaging follow-up (median follow-up duration: 8 months, range: 6–12 months) and continuous clinical serological monitoring was adopted to verify lesion properties. Two experienced nuclear medicine physicians independently and blindly interpreted all PET/CT images in random order, with consensus arbitration for discrepant results. Quantitative imaging parameters including SUVmax and SUVpeak were calculated for all target lesions. For lymph node metastatic lesion detection, [18F] FAPI-46 PET/CT exhibited significantly higher sensitivity (82.3
18F-SynVesT-1 is a PET tracer targeting synaptic vesicle protein 2A, a surrogate marker of synaptic density. Simplified quantification using pseudo-reference regions such as the centrum semiovale (CSO) or whole cerebellum (CER) has previously been validated in healthy volunteers and Alzheimer’s disease. This study assessed how motion correction and white-matter hyperintensities (WMH) affect 18F-SynVesT-1 quantification. We reconstructed 18F-SynVesT-1 images for 40 healthy volunteers and 31 patients with Alzheimer’s disease 60-90 minutes post-injection with 3 motion handling methods: no motion correction; 5 minute frame-based post-reconstruction coregistration and averaging, and a high-temporal-resolution data-driven motion correction applied during reconstruction. WMH were segmented from T2-FLAIR images and excluded from the CSO to generate lesion-corrected CSO regions. A region-based voxelwise partial volume correction was applied. SUV and SUVRCSO/CER were compared across motion- and lesion-handling methods and the effects on group differentiation were explored. Data-driven motion correction during reconstruction improved visual image sharpness and increased SUV in high-binding cortical regions (median +0.3-1.0
PSMA PET can accurately localize PSMA-expressing lesions. However, PSMA expression is not limited to prostate cancer cells but is also widely present in the neovascular endothelial cells of various solid tumours. We present a case of urothelial carcinoma of the bladder with multiple bone metastases. This case highlights that ¹⁸F-PSMA-1007 PET/CT improved visualization of the primary bladder lesion and demonstrates that ¹⁸F-PSMA-1007–avid osteoblastic bone metastases can originate from bladder cancer.
Peripheral nerve injury induces inflammatory and stress-related remodeling in downstream skeletal muscle before overt atrophy develops, yet non-invasive approaches capable of detecting and anatomically localizing early muscle involvement remain limited. The 18-kDa translocator protein (TSPO), a marker of inflammatory activation and mitochondrial stress, is a molecular target for PET imaging with [1⁸F]DPA-714. This study aimed to determine whether TSPO-targeted PET imaging enables early and spatially resolved detection of denervation-induced skeletal muscle injury distal to a peripheral nerve lesion. Adult mice underwent unilateral sciatic nerve crush. One-week post-injury, static [1⁸F]DPA-714 PET imaging was performed to assess tracer uptake in hindlimb skeletal muscle. Uptake was quantified and compared between injured and contralateral limbs as well as with sham-operated mice. Ex vivo validation included CD68 immunofluorescence, Western blot analysis of TSPO expression, and laminin-based muscle fiber morphometry. [1⁸F]DPA-714 uptake was significantly increased in distal hindlimb of crush-injured mice compared with contralateral and sham models. PET signal was selectively confined to denervated muscle distal to the lesion. Tracer uptake ratio between injured and contralateral hindlimb clearly discriminated crush-injured from sham animals without overlap. Immunofluorescence demonstrated marked macrophage infiltration, Western blot confirmed increased TSPO protein levels, and laminin morphometry revealed reduced muscle fiber size consistent with early atrophic remodeling. TSPO-targeted PET with [1⁸F]DPA-714 enables an early and anatomically selective detection of denervation-induced skeletal muscle injury distal to the nerve lesion, supporting its role as a translational imaging biomarker of peripheral nerve-muscle interaction during acute reversible nerve damage.
To evaluate whether 99mTc-MIP-1404 CZT SPECT/CT is non-inferior to 68Ga-PSMA-11 PET/CT for metastases detection in patients with newly diagnosed high risk prostate cancer (PCa). Patients with newly diagnosed high-risk PCa (age range 50–79 years, mean 66) underwent three imaging modalities: 99mTc-HDP CZT SPECT/CT, 68Ga-PSMA-11 PET/CE-CT (contrast-enhanced CT), and 99mTc-MIP-1404 CZT SPECT/CT. Metastatic involvement of lymph nodes (LN) and bones were recorded. Repeated-measures ANOVAs and post-hoc analyses were used to compare modality performance. Sensitivity and specificity for LN and skeletal lesions were calculated based on PET scans as the reference standard. 99mTc-MIP-1404 CZT SPECT/CT-based therapy decisions were compared to 68Ga-PSMA-11 PET/CT-based decisions. Sensitivity of 99mTc-MIP-1404 CZT SPECT/CT for metastasis detection at the patient level was 81
The c-Met receptor is a key therapeutic target in non-small cell lung cancer (NSCLC). Current methods for assessing c-Met level, are limited by biopsy sampling, which fails to account for spatio-temporal and intra-tumour heterogeneity. This study aims to evaluate the use of PET/CT imaging for non-invasive, full-body quantification of c-Met expression in different subtypes of NSCLC, encompassing both ADC and squamous cell carcinoma and compare it to MET gene alterations and IHC c-Met scoring. [68Ga]Ga-EMP-100, a PET radiotracer targeting c-Met, was radiolabelled and characterized. Cell-Derived Xenograft (CDX) models of NSCLC with different characteristics were developed and validated for PET/CT imaging using [68Ga]Ga-EMP-100. Tumour uptake and heterogeneity were quantified and compared to c-Met expression determined by IHC (H-score using SP44 and EP1454Y antibodies) and MET gene amplification detected by FISH and NGS. Automated radiolabelling of [68Ga]Ga-EMP-100 demonstrated a high radiochemical yield (RCY) and purity (RP). Pharmacokinetics studies revealed rapid excretion predominantly by the renal pathway. PET/CT imaging resulted in high contrast and enabled non-invasive classification of CDX models regarding c-Met receptor levels. The highest tumour uptake was observed in H1648 and EBC-1 models. Although MET gene alterations were not correlated with c-Met protein expression at the cell surface, a good correlation was found between SUVmax and c-Met expression, when using the EP1454Y antibody. PET/CT imaging using [68Ga]Ga-EMP-100 successfully quantified c-Met expression in vivo, clearly adding up to conventional IHC and genetic methods. Our study adds novel comparative evidence across tumour histotypes, providing new insight into how tumour phenotype affects c-Met–targeted imaging. This radiotracer holds potential as a non-invasive tool for selecting patients for c-Met-targeted therapies and monitoring therapeutic response in NSCLC. Further clinical studies are warranted.
Yttrium-90 labeled microspheres based selective internal radiotherapy (90Y-SIRT) is an established local-regional therapy for unresectable hepatocellular carcinoma (HCC) which demonstrating significant survival improvements in multiple clinical trials. Post therapeutic 90Y imaging is essential for in vivo 90Y microspheres biodistribution evaluation and absorbed dose estimation. We aim to study the effects of 90Y bremsstrahlung imaging parameters including energy window center, width and acquisition time on the quality of 90Y SPECT/CT to provide optimal imaging conditions after 90Y-SIRT. Using the NEMA IEC NU2 body phantom and Siemens Symbia™ T16 SPECT/CT scanner equipped with a high-energy general-purpose collimator (HEGPC), seven energy window settings and two acquisition times (20s / frame and 40s / frame) were investigated and analyzed. 90Y bremsstrahlung imaging with 94 keV ± 40
Abstract Background Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of β-amyloid (Aβ) in cerebral vessel walls, predominantly Aβ 1−40 , and frequently co-occurs with Alzheimer’s disease (AD). Reliable in vivo discrimination between vascular and parenchymal Aβ deposits (PEA) in AD is crucial for the assessment of CAA-related risks in anti-Aβ immunotherapies. Current Aβ PET tracers lack the ability to distinguish between vascular and parenchymal Aβ. The phenoxazine derivatives resorufin and ethyl-resorufin were previously shown to bind preferably to CAA over PEA. We therefore evaluated the fluorine-18-labeled resorufin derivative, [ 18 F]fluoroethylresorufin ([ 18 F]FER) as a potential PET tracer for selective in vivo detection of vascular Aβ. Results The binding specificity of [ 3 H]FER was assessed using recombinant Aβ 1−40 and Aβ 1−42 fibrils as well as in vitro autoradiography on mouse brain tissue of APP23 (CAA+/PEA+) and APPPS1 (CAA-/PEA+) models, and compared to those of [ 3 H]PIB. [ 18 F]FER and its deuterated analog were synthesized for evaluation of brain pharmacokinetics, metabolism, and in vivo binding using PET imaging in wild-type, APPPS1, and APP23 mice. [ 3 H]FER bound with higher affinity to Aβ 1−40 (K d = 9.4 nM) than to Aβ 1−42 (K d = 89.1 nM), consistent with its intended CAA selectivity. Autoradiography revealed preferential labeling of vascular amyloid in APP23 mice, with minimal binding in APPPS1 and wild-type tissue. In vivo, [ 18 F]FER exhibited high brain uptake (peak SUV = 1.5) and rapid clearance, but metabolic degradation was fast, with ~ 45% parent fraction remaining in the brain at 15 min. Deuteration did not improve stability but did improve washout kinetics. PET imaging with (d 4 )-[ 18 F]FER demonstrated a cortical uptake pattern similar to [ 11 C]PIB, indicating non-selective binding in vivo. Conclusions [ 18 F]FER showed promising in vitro affinity for vascular amyloid but lacked in vivo selectivity, likely due to rapid metabolism and high lipophilicity. These findings highlight the challenges of achieving in vivo CAA specificity and provide guidance for the optimization of future tracers targeting vascular Aβ pathology.
Prostate cancer is a prevalent disease with diverse tumor characteristics that complicate treatment. The integration of spatial patterns from prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), pathology and expanding genomic data represents a groundbreaking advancement in histo-imaging genomics. The aim of this study was to elucidate the internetwork mapping between genetic biomarkers and PSMA PET/CT imaging in prostate cancer patients. mRNA sequencing and clinical data from 433 prostate cancer patients were retrieved from The Cancer Genome Atlas (TCGA) database. Differential gene expression between the Gleason score (GS) > 7 and GS ≤ 7 groups was analyzed. Feature selection was performed following the univariate and multivariate logistic regression analyses. A GS predictive model was developed using multivariate logistic regression. Additionally, local samples and images from 27 patients were collected. PSMA PET/CT imaging was performed before radical prostatectomy, and mRNA sequencing of prostate cancer lesions was conducted using next-generation sequencing. Differentially expressed genes identified from the TCGA dataset were subsequently analyzed for correlations with PET-related metrics in the local dataset by utilizing Pearson correlation analysis.Out of the TCGA dataset, 174 genes exhibited differential expression. After feature selection, 53 genes remained. In the local dataset, ten genes (EFNA2, CACNA1I, CA1, MYBPC3, CYP1A1, TLCD3B, LRTM2, GBX2, SPSB4, and GDF3) demonstrated significant associations with PET-related metrics. When comparing the differential expression of genes between the GS>7 and GS≤7 groups, six genes (STMN2, CYP1A1, THRSP, LIPC, GBX2, and SPSB4) in the GS>7 group and eight genes (FBXL16, KLK14, DIRAS2, TERB2, PRAME, UTS2B, UGT2B15, and LINC02798) in the GS≤7 group were significantly correlated with PET-related parameters. This study identified genetic markers significantly correlated with PSMA PET/CT imaging features in prostate cancer patients. These findings may provide a valuable foundation for optimizing prostate cancer diagnostic procedures and tailoring therapeutic approaches based on genetic and imaging biomarkers.
The enzyme lysine-specific histone demethylase 1 (LSD1) epigenetically regulates gene expression and is a pharmacological target of interest in neurology. The aims of this study were to characterize the novel LSD1 brain PET tracer [18F]MNI-1054 in humans for the first time, including whole body radiation dosimetry and test-retest repeatability, and then utilize it to determine the enzyme occupancy of the brain-penetrant LSD1 inhibitor TAK-418. PET scans were acquired 6 h and 26 h following single oral doses (1.5 mg, 10 mg or 30 mg) of TAK-418. Due to the irreversible binding of both compounds to the same LSD1 binding site and the presence of residual circulating TAK-418 at the later scan time, a binding model was developed and applied to account for ongoing irreversible binding and enzyme turnover, and to simultaneously estimate the Day 1 and Day 2 enzyme occupancies and the apparent LSD1 enzyme turnover rate using data from all three dose cohorts. Kinetic brain PET data were most accurately modeled by an irreversible two-tissue compartment model. The highest and most reproducible signal was observed in the cerebellum, for which an acquisition time of 120 min was sufficient to maintain accurate and reliable estimates of Ki. Within the limits of the three TAK-418 dose levels assessed, the binding model estimated a maximum occupancy of 85–86
Manual segmentation of prostate cancer metastases on PSMA PET/CT and SPECT/CT is time-consuming and poorly scalable, particularly in highly metastatic patients. This study evaluated nnU-Net–based automatic segmentation models trained on PET and SPECT either separately or jointly and assessed whether PET-derived information can improve SPECT lesion segmentation. Seventy-three patients with metastatic castration-resistant prostate cancer treated with ¹⁷⁷Lu-PSMA were retrospectively included: 48 from the Henri Becquerel Cancer Center (HBCC) and 25 from Nantes University Hospital (NUH). For each patient, ⁶⁸Ga-PSMA PET/CT and ¹⁷⁷Lu-PSMA SPECT/CT were acquired before and during the first treatment cycle respectively. All images were manually segmented by four nuclear medicine physicians in consensus. Four nnU-Net models were trained: M1 (PET/CT only), M2 (SPECT/CT only), M3 (joint PET/CT+SPECT/CT, unimodal input at inference), and M4 (SPECT/CT with PET/CT segmentation as a priori input). Models were first trained and internally validated on HBCC data, then retrained on the full HBCC cohort and externally validated on NUH data. For PET/CT segmentation, M1 and M3 achieved comparable performance. M1 reached DSCs of 0.83 ± 0.19 (internal) and 0.76 ± 0.22 (external), while M3 achieved 0.83 ± 0.16 (internal) and 0.77 ± 0.21 (external). For SPECT/CT, the PET-guided model M4 (DSC: 0.63 ± 0.24 internal; 0.78 ± 0.14 external; PPV: 0.65 ± 0.26 internal; 0.75 ± 0.23 external) provided the best results. Compared with the SPECT-only model M2 (DSC: 0.61 ± 0.26 internal; 0.70 ± 0.25 external; PPV: 0.63 ± 0.25 internal; 0.71 ± 0.24 external), M4 showed no statistically significant difference in internal validation (DSC p = 0.35), while being statistically significant in external validation (DSC p = 0.014). The nnU-Net framework enables accurate lesion segmentation on both ⁶⁸Ga-PSMA PET/CT and ¹⁷⁷Lu-PSMA SPECT/CT. While PET-only and joint PET+SPECT models perform similarly on PET images, incorporating PET-derived segmentations as prior information tends to improve SPECT/CT lesion segmentation. This PET-guided SPECT segmentation strategy leverages the higher spatial resolution of PET and represents a key step towards fully automated extraction of volumetric and dosimetric biomarkers for personalized prostate cancer treatment.
