68 Ga-NY104 is a novel tracer targeting carbonic anhydrase IX (CAIX) with promising diagnostic efficacy for clear cell renal cell cancer. We present a 55-year-old woman with a suspected left renal mass who underwent 68 Ga-NY104, showing no significant uptake in the renal mass but incidentally revealing an intense uptake nodule in the left breast. Subsequent 18 F-FDG PET/CT revealed mild renal mass and intense breast nodule uptake. Postoperative pathology confirmed the renal mass as benign angiomyolipoma and the breast nodule as invasive ductal carcinoma. This case highlights the inclusion of primary breast cancer in the differential diagnosis of extra-renal CAIX-avid lesions.
BACKGROUND:Accurate preoperative lymph node (LN) staging is critical for determining optimal surgical strategies in duodenal and pancreatic neuroendocrine neoplasms (DP-NENs). While both gallium-68-labeled somatostatin receptor (SSTR) PET/CT and contrast-enhanced CT (ceCT) offer distinct advantages for LN assessment, their comparative diagnostic accuracy remains undefined. We aimed to systematically evaluate and directly compare the diagnostic performance of 68 Ga-SSTR PET/CT and ceCT against pathologic gold standards in DP-NENs. RESULTS:We retrospectively analyzed 521 LNs from 136 regional stations in 42 DP-NEN patients who underwent preoperative 68 Ga-SSTR PET/CT and ceCT followed by surgical LN dissection at 2 medical centers. Pathologic validation revealed comparable detection rates for 68 Ga-SSTR PET/CT and ceCT at the patient and regional levels. However, at the individual lesion level, 68 Ga-SSTR PET/CT demonstrated significantly higher sensitivity (67.6% vs. 26.4%, P =0.008) and accuracy (96.5% vs. 94.0%). In patients with small DP-NENs (≤2 cm), 68 Ga-SSTR PET/CT also exhibited superior lesion-level sensitivity (52.6% vs. 26.3%, P =0.004) and accuracy (94.0% vs. 93.5%). The size of the metastatic deposit within LNs significantly influenced 68 Ga-SSTR PET/CT detection ( P =0.036), whereas the overall LN size was associated with ceCT performance ( P =0.048). CONCLUSIONS:68 Ga-SSTR PET/CT provided superior detection of lymph node metastases (LNM) compared with ceCT. Preoperative integration of 68 Ga-SSTR PET/CT, particularly in conjunction with ceCT, might enhance staging accuracy, guiding less aggressive surgical approaches and avoiding nontargeted lymphadenectomy, especially in patients with small DP-NENs.
Fibroblast activation plays a key role in plaque instability and coronary artery disease (CAD) progression. In-stent restenosis (ISR) remains a major complication after percutaneous coronary intervention (PCI), increasing the risk of major adverse cardiovascular events (MACEs). This study primarily aimed to investigate whether coronary [¹⁸F]AlF-NOTA-FAPI-04 uptake is associated with major adverse cardiovascular events (MACEs) in symptomatic post-PCI patients, and secondarily to explore its ability to differentiate ISR from in-stent non-restenosis (ISnR) and to evaluate longitudinal changes under lipid-lowering therapy. In this prospective single-centre observational cohort study, we enrolled symptomatic CAD patients with a history of PCI A total of 76 symptomatic CAD patients (30 with acute coronary syndrome [ACS] and 46 with stable coronary syndrome [SCS]) underwent FAPI PET/CT imaging. Twenty-two non-CVD individuals served as controls. Coronary SUVmax and TBR were measured. The primary endpoint was the occurrence of MACEs, while the secondary endpoint was changes in FAPI uptake on follow-up PET/CT. The effects of Lipid-lowering therapy(LLT) on coronary FAPI uptake were also evaluated. FAPI uptake was significantly higher in ACS (SUVmax: 4.06 ± 1.81, TBR: 4.51 ± 2.20) than in SCS (SUVmax: 2.47 ± 1.82, TBR: 2.89 ± 2.23, P < 0.05). ISR plaques exhibited markedly elevated FAPI uptake (SUVmax: 4.06 ± 1.91, TBR: 4.69 ± 2.25) compared to ISnR plaques (SUVmax: 1.69 ± 0.72, TBR: 1.88 ± 0.91, P < 0.0001). Exploratory analyses suggested a trend toward higher MACE risk with elevated uptake, but survival differences were not significant. FAPI PET/CT enables non-invasive assessment of fibroblast-driven plaque activity, particularly in ISR, and identifies high-risk coronary plaques linked to MACEs. While LLT did not significantly modify fibroblast activity in the short term, further studies are needed to explore its long-term effects on plaque stability. (FAPI-PLAQUE Study, NCT06280287).
Small-molecule PET tracers targeting carbonic anhydrase IX (CAIX) have recently been developed for patients with clear cell renal cell carcinoma (ccRCC). Here, we report the preclinical results and first-in-human study of a CAIX-targeting theranostic pair, [68Ga]Ga/[177Lu]Lu-NYM096, for patients with metastatic ccRCC, aiming to assess its safety, tolerability, dosimetry, and preliminary efficacy. Methods: The in vivo biodistribution of [68Ga]Ga-NYM096 was evaluated in mice bearing OS-RC-2 xenografts. The therapeutic efficacy of [177Lu]Lu-NYM096 was assessed with a dose escalating from 8.1 to 74 MBq. Patients with metastatic ccRCC who had disease progression after standard therapy were prospectively enrolled. Serial whole-body [68Ga]Ga-NYM096 PET/CT scans were performed to evaluate biodistribution and dosimetry. Patients with positive CAIX expression entered the therapeutic phase and received [177Lu]Lu-NYM096 following a standard 3-plus-3 dose escalation design that started from 1.85 GBq. Serial whole-body planar imaging was performed after the first therapy cycle. Safety, dosimetry, and preliminary efficacy were evaluated. Results: High tumor accumulation of [68Ga]Ga/[177Lu]Lu-NYM096 was observed in OS-RC-2 xenograft tumor models. Moreover, [177Lu]Lu-NYM096 was well tolerated and demonstrated a significant dose-dependent tumor suppression effect. In the 2 patients, [68Ga]Ga-NYM096 demonstrated excellent tumor uptake, with an SUVmax of 330.0 at 1 h postinjection. Subsequent [177Lu]Lu-NYM096 treatment demonstrated no evidence of nephrotoxicity, hepatotoxicity, or pancreatic toxicity. Patient 1 experienced grade 1 gastric side effects and anemia, whereas patient 2 developed grade 3 radiation-induced gastritis. Follow-up [68Ga]Ga-NYM096 PET/CT evaluations showed evidence of tumor response to [177Lu]Lu-NYM096 treatment. Conclusion: This is early evidence that the CAIX-targeting theranostic pair [68Ga]Ga/[177Lu]Lu-NYM096 is feasible, offering a strategy for patients with end-stage ccRCC. The gastric toxicity proposes a significant challenge for CAIX-targeting radiopharmaceutical therapy.
Background Parkinson’s disease (PD) and multiple system atrophy parkinsonian subtype (MSA-P) are clinically similar α-synucleinopathies, making differential diagnosis challenging. This study aimed to identify distinct regional dopaminergic dysfunction patterns using quantitative 18F-DOPA PET to differentiate the two disorders. Methods We prospectively recruited 20 PD patients, 12 MSA-P patients, and 9 healthy controls. All underwent 18F-DOPA PET imaging. Images were normalized using an adaptive probabilistic brain atlas. Voxel-wise and region-of-interest (ROI) analyses were performed with Statistical Parametric Mapping 12, controlling for age, sex, and disease duration. ROI comparisons used ANCOVA with Bonferroni post-hoc tests. Results Both patient groups showed severe putaminal dopaminergic loss compared to controls. A key differentiator was caudate nucleus involvement: SUVR was significantly lower in MSA-P than in PD (P = 0.031) and controls (P = 0.006), while PD did not differ from controls. Cerebellar SUVR was also significantly reduced in MSA-P compared to PD (P = 0.026) and controls (P = 0.007), despite no clinical cerebellar signs in MSA-P patients. Putamen uptake did not differentiate PD from MSA-P. Voxel-wise analysis confirmed reduced uptake in bilateral caudate, posterior cerebellar lobes, and vermis in MSA-P vs PD. No significant correlations between SUVR and clinical severity were found after correction for multiple comparisons. Conclusions 18F-DOPA PET reveals distinct topographic patterns: PD shows predominant putaminal impairment with caudate sparing, whereas MSA-P is characterized by concurrent caudate and cerebellar dopaminergic dysfunction. Caudate and cerebellar 18F-DOPA uptake are potential imaging biomarkers for differentiating MSA-P from PD.
This study aims to investigate the prevalence, pattern, physiological basis, and influencing factors of sympathetic ganglia uptake on [18F]AlF-NOTA-LM3 PET/CT. [18F]AlF-NOTA-LM3 PET/CT images from 101 patients were retrospectively reviewed to evaluate the presence of sympathetic ganglia uptake. Clinical data and normal-organ uptake were investigated to identify influencing factors. Uptake patterns were compared between sympathetic ganglia and metastatic lymph nodes. Immunohistochemical (IHC) staining for SSTR2 was performed on a stellate ganglion and other specimens. Positive sympathetic ganglia were observed in 76.2
PRIMARY score uses intraprostatic uptake patterns and uptake intensity of PSMA and has good performance in identifying clinically significant prostate cancer (csPCa). However, diagnostic accuracy is not satisfying in patients with PRIMARY score of 3 and 4, which may account for the relatively low specificity of PRIMARY score. MRI may improve the accuracy of PRIMARY score. This study aims to investigate the added value of bpMRI to Al18F-NOTA-PSMA-617 PET/CT in diagnosis of csPCa. This is a retrospective analysis of a prospectively collected dataset. Al18F-NOTA-PSMA-617 PET/CT and bpMRI were performed within 3 months in patients with suspected PCa. PRIMARY scores were evaluated in a blinded manner by two nuclear medicine physicians independently. Lesions with PRIMARY score of ≥ 3 were classified as malignant. Besides, lesions with PRIMARY score 3 or 4 underwent further diagnostic refinement via bpMRI. Pathology was obtained within three months after completing bpMRI and PSMA PET/CT. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. 181 patients were included in this analysis. The incidence of csPCa in PRIMARY score 1–5 is 0 (0/18), 7.7
This study aimed to investigate in vivo fibroblast activation in hypereosinophilic syndrome (HES) with cardiac involvement, and to explore the correlation between fibroblast activation protein inhibitor (FAPI) uptake and eosinophil-related biomarker-eosinophil extracellular traps (EETs). This study enrolled 20 patients diagnosed with HES and cardiac involvement. All patients underwent Al18F-FAPI-04 PET/CT imaging, transthoracic echocardiography, as well as measurement of absolute eosinophil count (AEC) and EETs levels. Among the 20 patients enrolled, 16 patients were diagnosed with reactive HES and 4 with idiopathic HES. Elevated FAPI uptake was observed across different stages of disease course. Myocardial Al18F-FAPI uptake was observed in all patients (20/20), with an extensive pattern in 15 and a patchy pattern in 5. Quantitative uptake was significantly higher in the extensive pattern group (maximum standardized uptake value (SUVmax): 6.58 [5.01–8.62] vs. 2.44 [1.91–2.76], p < 0.001). Segmental analysis revealed higher FAPI uptake in apical and mid-ventricular segments compared to basal segments (SUVmax: apical, 4.67 [1.94–6.89] vs. middle, 4.25 [2.33–5.61] vs. basal, 3.44 [2.46–5.23], p = 0.022). FAPI-PET/CT identified a higher proportion of involved myocardial segments (83.2
Among oligodendrogliomas, World Health Organization (WHO) grade 2 tumors have relatively more favorable prognosis compared to the grade 3. However, heterogeneity in tumoral behavior exists in grade 2 oligodendrogliomas, with some exhibiting an aggressive course. The authors applied [18F]FET-PET in oligodendrogliomas and extended its utility in predicting prognosis of low-grade oligodendrogliomas. Twelve consecutive patients with oligodendrogliomas treated at our institution (Oligo-WHO2: n = 8; Oligo-WHO3: n = 4) were enrolled. All patients underwent contrast-enhanced MRI and [18F]FET-PET/MR before surgery. Maximum and mean target-to-background ratios (TBRmax, TBRmean) were evaluated, and progression-free survival (PFS) was recorded. Bulk RNA sequencing and immunohistochemical(IHC) staining were performed for the verification of [18F]FET-PET findings. All grade-3 oligodendrogliomas presented high [18F]FET uptake on PET and contrast-enhancement on MRI. Although all grade-2 tumors were non-enhanced, only 50
The comprehensive knowledge of how the distinct physical decay characteristics of each radionuclide shape their image quality performance is essential for tailoring acquisition protocols and ensuring optimal clinical applications. Understanding the spatial dependence of the contrast recovery coefficient (CRC) is a prerequisite for robust quantitative image analyses and accurate clinical interpretations, since the partial volume effect (PVE) and the count rate vary along the axial field of view (AFOV). Image quality assessments with various radionuclides were performed on the uMI Panorama GS PET/CT system, with the CRC profile across its extended AFOV also evaluated. Following the NEMA NU 2-2018 standard, the image quality was assessed using the NEMA IEC (NEC) Body Phantom with 18F, 64Cu, 68Ga, 89Zr, 124I, and 90Y. The CRC, the background variability (BV), and the lung residual error were measured to quantify the image quality. CRCs were sequentially measured at four axial offsets: 1/2, 1/4, 1/8, and 1/16 of the AFOV. The impact of the radionuclide-specific PSF (point spread function) modeling on the CRC was evaluated by comparing PET images reconstructed with and without PSF modeling. The assessment demonstrated comparable image qualities for 18F, 64Cu, 68Ga, 89Zr, 124I, while 90Y showed a similar CRC but a higher BV and a higher lung residual error, attributable to its low positron branching ratio. The BV and lung residual error increased with increasing axial distance from the AFOV center, whereas CRCs for larger spheres remained stable across AFOV positions; small-sphere CRC measurements exhibited increased dispersion toward the periphery due to reduced count statistics. The PSF modeling significantly improved CRCs for 68Ga and 124I, consistent with their long positron ranges. All investigated radionuclides were effectively imaged on the uMI Panorama GS PET/CT system. The AFOV uniformity was quantitatively evaluated based on CRC measurements obtained at multiple positions along the AFOV.
Abstract Background 177Lu-PSMA-617 is a radioligand therapy targeting cells expressing prostate-specific membrane antigen (PSMA). The pharmacokinetics, dosimetry, and safety of 177Lu-PSMA-617 in participants with metastatic castration-resistant prostate cancer are described previously. In this study, we describe the blood pharmacokinetics behavior, biodistribution, and dosimetry of 177Lu-PSMA-617 to support its clinical use in Chinese participants. Results Nine participants were infused with 177Lu-PSMA-617 (range: 6985.6–8036.0 MBq). The geometric (Geo)-mean blood terminal half-life was 52.6 h, corresponding to an effective half-life of approximately 40 h. The Geo-mean maximum blood concentration of 11.3 ng/mL was achieved at a median time of 0.217 h post administration. The Geo-mean volume of distribution and clearance were 123 L and 1.62 L/h, respectively. The lacrimal glands received the highest absorbed dose of 3.1 mGy/MBq (Geo-coefficient of variation, 93.7%), followed by the thyroid, kidneys, and salivary glands. The Geo-mean whole-body effective dose was 890 mSv (Geo-coefficient of variation, 112.4%). Conclusions The blood pharmacokinetics and organ dosimetry of 177Lu-PSMA-617 in Chinese participants with progressive metastatic castration-resistant prostate cancer were consistent with those previously reported. The cumulative absorbed dose, corresponding to six cycles of treatment, was consistent with published literature. This analysis was conducted as part of a phase II study registered as NCT05670106 at ClinicalTrials.gov on November 7, 2022.
ABSTRACT To evaluate the comparative prognostic utility of next‐generation flow cytometry (NGF) and dual‐tracer PET/CT in measuring minimal residual disease (MRD), this prospective real‐world study enrolled 118 newly diagnosed multiple myeloma (NDMM) patients. Patients underwent post‐treatment assessment using NGF (sensitivity 10−5) and dual‐tracer PET/CT using 11C‐acetate (AC‐PET) and 18F‐FDG. While AC‐PET showed a numerically higher detection rate compared to FDG‐PET in paired analyses (n = 45), a significant discordance was observed between imaging and immunophenotypic assessment. NGF detected MRD in 38.2% of paired cases compared to 11.8% by AC‐PET; however, AC‐PET uniquely identified metabolic activity in extramedullary sites for two NGF‐negative patients, highlighting the value of functional imaging in resolving spatial heterogeneity. In the landmark survival analysis (n = 104), NGF positivity was identified as a robust independent predictor for inferior progression‐free survival (HR 2.21, 95% CI 1.01–4.81; p = 0.046) and overall survival (HR 4.97, 95% CI 1.23–20.01; p = 0.026), transcending baseline risk stratifications. Furthermore, longitudinal monitoring revealed that patients achieving sustained MRD negativity experienced significantly superior outcomes compared to those with transient negativity or persistent disease. These findings establish NGF as the standard prognostic biomarker for MM, while AC‐PET serves as a critical complementary tool for detecting extramedullary escape, supporting a risk‐adapted MRD strategy that integrates molecular depth with metabolic imaging.
Background Interpreting and diagnosing cardiac PET images in the transaxial plane could complicate image assessment and hinder the detection of perfusion defects. Therefore, reorienting cardiac PET images from the transaxial plane to the short-axis plane is essential. Purpose A convolutional neural network (CNN)-based method for anchor point detection was proposed to enable the automatic reorientation of 11C-acetate cardiac PET images. Methods A total of 57 subjects who underwent 11C-acetate PET/CT imaging were enrolled in this study. Forty subjects were assigned to the training set, and 17 subjects to the testing set. Three anchor points (the apex of the left ventricle, the center of the left ventricle base and the center of the right ventricle) were manually annotated and used as the gold standard. A 3D CNN incorporating residual modules and fully connected layers was developed to predict the coordinates of three anchor points. A composite loss function was designed to guide the model training. Results The predicted coordinates demonstrated a significant correlation with the gold standard (ICCs > 0.75, p < 0.05). Across 17 segments, the average normalized root mean square error (NRMSE) was below 0.082, and the average relative difference was less than 8.69%. No significant differences in pharmacokinetic parameters were observed between manual annotation and the proposed method (all p > 0.05). An NRMSE of 0.053 was achieved on the simulated pseudo image. Conclusions The 3D CNN-based method for anchor point detection demonstrated performance comparable to the manual approach, providing a novel and effective solution for the reorientation of 11C-acetate cardiac PET image.
PURPOSE:To evaluate whether mucosal boron heterogeneity measured using fluoro-boronophenylalanine positron emission tomography (18F-BPA PET) improves the prediction of oral mucositis in boron neutron capture therapy (BNCT), and to establish an imaging-guided framework for normal tissue complication probability (NTCP) modeling. METHODS AND MATERIALS:This retrospective study analyzed 45 BNCT treatment sessions for head and neck cancer. Pre-treatment 18F-BPA PET was used to quantify PET-derived mucosal uptake and to derive an uptake-defined mucosal region using a tissue-to-blood ratio (TBR) threshold of 1.8. Four mucosal dose-calculation workflows were compared: (1) the Finnish workflow and (2) the Japanese workflow-both delineating mucosa anatomically and assuming uniform boron concentration implemented via a fixed TBR; (3) anatomical mucosa and (4) uptake-defined mucosa with heterogeneous boron distribution derived from PET-derived uptake heterogeneity. Biological (Gy-equivalent) and physical (Gy) subvolume dose metrics, including dose to the hottest 0.05 cubic centimeters (D0.05cc), were evaluated for correlation with mucositis severity, discrimination of grade ≥ 2 toxicity, and suitability for NTCP modeling. RESULTS:18F-BPA PET demonstrated pronounced functional heterogeneity across the mucosa. Among all evaluated metrics, uptake-defined biological D0.05cc showed the strongest and most consistent association with toxicity, fulfilling all NTCP validity criteria yielding the highest discriminative performance (repeated cross-validated area under the curve, 0.738 ± 0.025) and physiologically plausible TD10-TD90 thresholds (4.85-12.84 Gy-equivalent). In contrast, Finnish and Japanese anatomical maximum-dose metrics, based on uniform-boron assumptions, showed no meaningful correlation with clinical outcomes. CONCLUSIONS:Functional PET imaging reveals clinically important mucosal heterogeneity that influences BNCT toxicity. The uptake-defined biological D0.05cc demonstrated superior prediction of oral mucositis and may provide a promising hypothesis-generating framework for developing patient-specific mucosal dose constraints, pending prospective validation.
This study aimed to evaluate the value of integrated 18F-NOTA-FAPI-04 PET/MRI for CAS-defined clinical activity assessment in thyroid-associated ophthalmopathy (TAO) by investigating the correlation between PET- and multi-parametric MRI-derived features and their predictive performance. A total of 33 TAO participants were prospectively enrolled and underwent intergrated 18F-NOTA-FAPI-04 PET/MRI. According to the Clinical Activity Score (CAS), Eyes were classified as active (CAS ≥ 3) or inactive (CAS<3). For patient-level analysis, participants were classified as inactive only when both eyes were inactive; otherwise, they were classified as active. PET-derived parameters (maximum standardized uptake value [SUVmax], mean standardized uptake value [SUVmean], metabolic tumor volume [MTV], and total lesion FAPI uptake [TLF]), as well as first-order features (mean, minimum, maximum, median, skewness, and kurtosis) from MRI-derived parametric maps (normalized T2-weighted imaging-derived parameter [T2WI], heterogeneity index [α], distributed diffusion coefficient [DDC], diffusion coefficient [D], true relative blood flow [rBF], mean diffusivity [MD], and mean kurtosis [MK]) were extracted. Repeatability was assessed using the Dice similarity coefficient (DSC) of VOIs delineation and the intraclass correlation coefficient (ICC) for quantitative parameters. Correlation analyses between PET and MRI features, comparisons between active and inactive group, and discriminative performance evaluations of PET, MRI, and combined PET/MRI models were performed at both patient and eye levels. Support vector machine (SVM) and receiver operating characteristic (ROC) analysis were performed to compare discriminative performance. VOIs delineation demonstrated good interobserver and intraobserver agreement, with DSC of 0.850 (95