Positron Emission Tomography/Computed Tomography (PET/CT) imaging has emerged as an important tool with growing potential in the diagnosis, staging, and monitoring of pancreatic cancer, though its clinical implementation varies across different healthcare systems. This study aims to analyze the global research landscape and emerging trends in PET/CT for pancreatic cancer through a comprehensive bibliometric analysis. A bibliometric analysis was conducted using the Web of Science Core Collection to gather literature. The bibliometric tools VOSviewer, CiteSpace, and the R package “bibliometrix” were employed to visualize collaboration networks, keyword co-occurrences, and emerging research trends. The analysis identified 381 publications on PET/CT in pancreatic cancer. The annual number of publications exhibited an overall increasing trend with a 13.56
Primary hyperoxaluria type 1 is a rare genetic disorder that leads to systemic oxalate deposition and end-stage renal disease. We describe 68 Ga-FAPI-04 PET/CT findings in a case of primary hyperoxaluria type 1. 68 Ga-FAPI-04 PET/CT showed striking FAPI uptake in multiple bones and joints. This FAPI distribution likely represents a unique imaging manifestation of the active fibroblastic repair process triggered by oxalate crystal deposition.
Abundant cancer-associated fibroblasts (CAFs) in pancreatic tumors cause robust interstitial fibrosis and abnormal vascular structure, hindering the delivery and effectiveness of small-molecule therapeutics, leading to poor clinical outcomes. We developed a strategy to modulate the extracellular matrix (ECM) in pancreatic cancer to enhance chemotherapy through sequential administration of TiO2 nanoparticles (NPs), [68Ga]Ga-FAPI-04 ([68Ga]Ga-FAPI), and the chemotherapeutic drug tirapazamine (TPZ). The positron emission tomography tracer [68Ga]Ga-FAPI specifically targets CAFs and serves as an internal excitation source for Cerenkov radiation-mediated photodynamic therapy (CR-PDT). TiO2 NPs generate cytotoxic reactive oxygen species upon CR, destroying tumor cells and CAFs. As a result, CR-PDT reduces the dense stromal barrier by inhibiting the formation and secretion of fibrous collagen, improving the delivery of TPZ. Additionally, CR-PDT consumes oxygen throughout the process, intensifying tumor hypoxia, which further activates TPZ, a hypoxia-activated and bio-reductive prodrug. Our design of CR-PDT-mediated ECM modulation brings new ideas for the exploration and application of radiotracer-combined nanomedicine in cancer therapy, particularly for cancers with abundant ECM.
Platinum-based chemotherapeutic agents are non-specific anticancer drugs known to induce multi-organ fibrosis and functional impairments. This study aimed to evaluate multi-organ fibrosis and functional impairments following platinum-based chemotherapy using 68Ga-FAPI-04 PET/CT imaging. 68Ga-FAPI-04 PET/CT imaging was performed to assess fibroblast activation in both preclinical and clinical settings. In the preclinical study, a cisplatin-induced multi-organ fibrosis model was established. Organ function and fibrosis were evaluated through blood tests, echocardiography, and histological staining. Tissue expression of fibroblast activation protein (FAP) was assessed by immunofluorescence staining. In the clinical study, 68Ga-FAPI-04 PET/CT images from 17 participants who received SOX (oxaliplatin plus Teysuno), S-1 (Teysuno), or no chemotherapy were analyzed to verify the presence of multi-organ fibrosis. In the preclinical study, renal fibroblast activation of the cisplatin-treated group increased from the first week, preceding the onset of impaired renal function by two weeks. Cardiac fibroblast activation increased from the second week, one week prior to the impaired cardiac function. Hepatic fibroblast activation increased from the third week, occurring two weeks after the onset of impaired liver function. Higher fibroblast activation was positively correlated with more severe organ fibrosis and greater functional impairment. In the clinical study, patients receiving SOX chemotherapy exhibited higher fibroblast activation compared with those receiving S-1 chemotherapy. 68Ga-FAPI-04 PET/CT imaging holds significant potential for the non-invasive detection of platinum-induced multi-organ fibrosis and for predicting subsequent organ functional impairments. This technique holds clinical value for guiding timely dose adjustments or switching to alternative anticancer therapies.
Background: Prostate-specific membrane antigen (PSMA) PET/CT can detect clinically significant prostate cancer (csPCa), but no validated multi-parameter reporting framework analogous to PI-RADS for mpMRI exists. We aimed to develop and externally validate a multi-parameter, rule-based integer PSMA PET/CT scoring system across multiple tracers. Methods: In this multicentre, diagnostic accuracy study, we derived C-SUDA-5 (China-Soochow University-5) using a development cohort (n=747; six centres; four PSMA tracers) through LASSO regression, converting five retained PSMA PET-derived parameters into an integer score (range −1 to 11; five risk groups). We externally validated in a temporal cohort (n=100, from the originating centre) and a spatial cohort (n=190, from an independent centre), comparing discrimination against PI-RADS, PRIMARY score, miPSMA, and a 5-point Likert scale. Findings: C-SUDA-5 yielded area under the curve (AUC) of 0·880 (development, four tracers) and 0·864–0·869 (two independent external cohorts), outperforming PI-RADS, PRIMARY, and miPSMA (all P<0·05). csPCa rates increased stepwise from 7–14% (G1) to 99–100% (G5). The recommended C-SUDA-5 strategy (G1 follow-up, G2–5 biopsy) achieved miss rates of 1·6–3·0% with correct avoidance rates of 19·0–20·0%. Interpretation: C-SUDA-5 discriminated csPCa with accuracy comparable to experienced nuclear medicine physicians (Likert mean AUC 0·875) with higher inter-rater reliability (grade kappa 0·990 vs 0·226). This rule-based integer scoring system may provide a standardised and reproducible approach to PSMA PET/CT reporting before biopsy. Prospective interventional trials are needed to evaluate clinical impact.
Background: To evaluate the performance of a Channel Dense Dense U-Generative Adversarial Network (CDDU-GAN), in restoring the quality of four-fold accelerated Prostate-Specific Membrane Antigen (PSMA) PET acquisitions across different radiotracers and hybrid imaging platforms. Methods: This prospective study enrolled 84 patients who underwent either 18F-PSMA or 68Ga-PSMA PET imaging on PET/CT or PET/MR systems. Standard-dose listmode data (120s/bed for PET/CT, 240s/bed for PET/MR) were retrospectively subsampled to simulate a rapid-scan protocol (30s/bed and 60s/bed, respectively). The CDDU-GAN was trained to transform these low-count images to a quality equivalent to the standard-dose acquisitions. Objective image quality was quantified using Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index (SSIM). Subjective image quality was independently assessed by two blinded nuclear medicine physicians using a 5-point Likert scale for overall quality, lesion conspicuity, and diagnostic confidence. Statistical significance was determined using the Wilcoxon signed-rank test. Results: The CDDU-GAN framework yielded significant improvements in objective quality for the total cohort, increasing the mean PSNR from 46.8±7.5 to 48.2±6.6 (p<0.0001) and SSIM from 0.980±0.026 to 0.986±0.020 (p<0.0001). Performance gains were more pronounced for PET/CT datasets (PSNR increase: +3.3 dB for 18F-PSMA; +2.5 dB for 68Ga-PSMA) than for PET/MR. Inter-rater reliability for subjective analysis was substantial to almost perfect. The CDDU-GAN-enhanced images received significantly higher scores than unprocessed fast-scan images across all subjective metrics (p<0.05). Notably, the model increased the mean diagnostic confidence score for the entire cohort from 3.37±1.27 to 3.78±1.22, substantially closing the gap to the standard-dose score of 4.22±1.23 and restoring diagnostic utility in challenging cases. Conclusion: The proposed CDDU-GAN framework effectively restores image quality and diagnostic confidence in four-fold accelerated PSMA PET imaging. By successfully mitigating noise and improving image fidelity across different tracers and platforms, this deep learning approach holds significant potential to increase patient throughput, reduce motion artifacts, and improve patient comfort without a critical loss of diagnostic information.
Acrometastasis is an uncommon presentation of lung cancer with poor prognosis. We describe bone scintigraphy and FDG PET/CT findings in a case of pulmonary nuclear protein in testis (NUT) carcinoma with only initial presentation of bony metastasis to the distal phalanx of the right little finger after traumatic injury. FDG PET/CT showed intense activity of the primary lung tumor with multiple FDG-avid lymph node, adrenal, bone, and cartilage metastases including unusual and unexpected metastases at the finger, mandibular condyle, and thyroid cartilage. Bone scintigraphy significantly underestimated the extent of osseous involvement because the osseous metastases appeared as non-osteoblastic lesions.
Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has become pivotal in prostate cancer (PCa) management, offering superior sensitivity over conventional imaging for detecting tumors, metastases, and biochemical recurrence. However, interpretive subjectivity, workflow inefficiencies, and heterogeneous PSMA expression remain significant limitations. Artificial intelligence (AI), particularly radiomics and deep learning, addresses these challenges by enabling automated lesion analysis and image enhancement. This review examines the impact of AI across the PSMA-PET workflow, covering optimized image acquisition (e.g., low-dose protocols, motion correction), enhanced interpretation (e.g., lesion characterization, prognostic stratification), and personalized theranostics (e.g., treatment response forecasting, radioligand therapy dosimetry). Despite promising multicenter validation, challenges remain in annotation standardization, data heterogeneity, model generalizability, interpretability, regulatory integration, and ethics. We further discuss emerging frontiers, including multimodal multi-omic integration, generative AI, and AI-driven clinical decision support systems. Notably, we highlight the evolving role of nuclear medicine physicians and radiologists as integrators of AI-derived biomarkers, who validate AI outputs for high-stakes decisions, retain interpretive authority for complex cases, and oversee quality assurance, ensuring that AI augments rather than replaces specialist expertise. These advances position AI-integrated PSMA-PET to drive precision oncology, with key pathways outlined for clinical translation and future innovation in PCa care.
Fibroblast activation protein (FAP) may contribute to radiotherapy resistance. This study aimed to compare baseline 18F-labeled fibroblast activation protein inhibitor (18F-FAPI) PET/CT and 18F-FDG PET/CT in short-term target lesion response (TLR) and clinical outcome prediction in unresectable hepatocellular carcinoma (uHCC) patients treated with Yttrium-90(90Y) resin microsphere selective internal radiation therapy (SIRT). Patients with uHCC undergoing pre-SIRT 18F-FDG and 18F-FAPI PET/CT were prospectively recruited. Semiquantitative parameters, including target/whole-body metabolic tumor volume (MTV-target/MTV-WB) and total lesion glycolysis (TLG-target/TLG-WB), were obtained from 18F-FDG PET/CT, while target/whole-body FAPI-avid tumor volume (FTV-target/FTV-WB) and total lesion FAP expression (TLF-target/TLF-WB) were derived from 18F-FAPI PET/CT. Voxel-based tumor absorbed dose(TAD) parameters for target lesions were calculated from post-SIRT PET/CT, including the mean TAD (Dmean) and TAD to 50
Transarterial radioembolization (TARE) with β-emitting radionuclides is widely used for hepatocellular carcinoma (HCC), but its clinical efficacy remains to be further improved. α-particle-emitting radionuclides possess high linear energy transfer (LET) and unique advantages in cancer therapy, motivating α-particle based composite platform. Accordingly, we engineer the first clinically mimetic α-TARE microsphere by in-situ ²²³Ra-doped calcium–alginate composite microsphere (²²³Ra/Ca-ALG MS) using a hydrogel matrix, in which alginate “egg-box” coordination captures Ra²⁺ to provide stable radiolabeling, delivered via selective hepatic arterial injection to HCC. The microspheres exhibited excellent radiolabeling stability (88
Targeted alpha therapy (TAT) with Astatine-211 (211At) has shown potent antitumor efficacy, yet free 211At released through deastatination accumulates in the thyroid via the sodium-iodide symporter (NIS), posing safety concerns distinct from β-emitter counterparts such as 131I. Here, we combine multimodal in vivo imaging and molecular profiling to resolve the kinetics-toxicity relationship of 211At- versus 131I-induced thyroid injury. Using serial 99mTcO4 - SPECT/CT and 18F-FDG PET/CT, we captured the dynamic evolution of thyroid function and metabolic inflammation in BALB/c mice receiving equipotent cytotoxic doses of Na131I (18.5 MBq), low-dose Na211At (18.5 kBq), or high-dose Na211At (92.5 kBq). Biodistribution study revealed rapid NIS-mediated uptake of 211At peaking at 7 h and complete clearance by 44 h, yet subsequent SPECT and hormonal analyses demonstrated progressive thyroidal dysfunction independent of residual activity. PET-based metabolic imaging confirmed persistent inflammatory stress despite radionuclide clearance. By integrating multimodal spatiotemporal imaging, cytokine profiling, RNA sequencing, and immune deconvolution techniques, we identified fundamental distinctions between α and β irradiation in immunopathological mechanisms. While β irradiation predominantly elicited transient innate immune activation, high-LET α-particle exposure preferentially shifted the thyroid immune landscape toward an antigen-experienced adaptive state. This immune remodeling may contribute to the persistence of thyroidal dysfunction and inflammatory stress following α-particle exposure, even after radionuclide clearance. This spatiotemporal imaging framework provides a mechanistic basis for understanding α-induced organ injury, challenges dose-centric safety models, and guides the design and monitoring of future TAT regimens.
We present the 18 F-FDG PET/CT findings of pancreatic metastasis in a 60-year-old man with a history of rectal cancer, who presented with abdominal discomfort and elevated carcinoembryonic antigen (CEA). 18 F-FDG PET/CT revealed a hypermetabolic pancreatic nodule with ductal dilation. Histopathology confirmed metastatic intestinal-origin adenocarcinoma. This case highlights the diagnostic challenge in differentiating metastasis from primary pancreatic cancer, particularly given the uncommon presentation of solitary pancreatic metastasis and its atypical imaging features. A comprehensive evaluation is essential for accurate diagnosis.
Dysregulated lipid metabolism, as seen in obesity, is closely linked to altered angiotensin-converting enzyme 2 (ACE2) expression in adipose tissue. However, real-time noninvasive monitoring of ACE2 dynamics in vivo remains a significant challenge. Therefore, we developed 18F-CC-Omi-X (Omi-X: HQPYRVVVLSFELLH), an ACE2-targeted PET tracer specifically designed for mapping ACE2 in lipid metabolic contexts. l-Propargylglycine (l-Pra) was modified to the C-terminus of Omi-X to suit 18F-labeling via the click-chemistry protocol, which minimized steric hindrance and preserved superior binding specificity compared to conventional N-terminus modification, as evidenced by a favorable IC50 (421 nM) in competitive binding assays. In diet-induced obese humanized ACE2 (hACE2) mice, 18F-CC-Omi-X PET showed high and specific uptake in adipose depots, with SUVmax strongly correlating with ex vivo ACE2 levels (r = 0.961, P < 0.05). Crucially, intervention with the ACE2 modulator ursodeoxycholic acid (UDCA) led to a significant decrease in tracer uptake in both subcutaneous and mesenteric fat, thereby enabling visualization of pharmacologically induced ACE2 downregulation in vivo. This work established 18F-CC-Omi-X as a vital molecular imaging tracer, enabling the noninvasive quantification of ACE2 dynamics directly within key lipid metabolic tissues, which is essential for elucidating its role in metabolic diseases and evaluating targeted therapies.
The modulation of immune checkpoint activity exerts profound impacts on tumor immunotherapy. However, the interfere of mature immune checkpoints encounter efficacy challenges in solid tumors, which underlies a critical barrier in clinical translation of multiple potential targets. Herein, we propose a biochemical immune modulation strategy for immunosuppression reversal by blocking the mature of CD47 within the endoplasmic reticulum (ER). Clinically used radionuclides iodine-131 (131I) is reengineered to encapsulate within microporous barium titanate nanoparticles, forming an immunoactive nanomodulator. Leveraging polarized and collisional relaxation, the electrons emitted from 131I mediate continuous disulfide bond reduction, blocking CD47 folding and surface translocation, resulting in a 93.6% reduction in CD47 expression. Together with the remarkable increase of tumor antigen presentation induced by ER reductive stress in pancreatic tumor-bearing mice, we realize a 93% tumor inhibition and a 3-fold prolongation of survival. This work underscores the role of organellar biochemistry in reshaping immunosuppression for tumor immunotherapy.
Accurate diagnosis and effective antiviral strategies are critical to combat acute infection and to avoid damage to the host. Due to their restricted radiation range and energy, Auger electron emitters have shown potential as a RNA-destructing radionuclide therapy in oncology and infection. Focusing on the process of angiotensin-converting enzyme 2 (ACE2)-mediated endocytosis, Technetium-99m-labeled DX600 (99mTc-DX600) was synthesized as an Auger electron vector to specifically bind to surface-expressed ACE2 proteins on 293T-hACE2 cells (293T cells stably expressing human ACE2), and Technetium-99m-loaded microvesicles (99mTc-MVs) served as an antiviral tracer and effector in pseudovirus infection. The whole-body ACE2 expression evaluation was non-invasive, meanwhile, the enhanced green fluorescent protein expression of pseudoviruses was substantially inhibited as a result of the 99mTc-DX600 loading of microvesicles, though the mitochondrial and DNA stabilities of the host cells were not affected. Furthermore, the in vivo distribution of 99mTc-DX600 in humanized ACE2 mice was demonstrated to be both ACE2-specific and long-lasting, and an antiviral effect was fully exhibited with two cycles of intravenous injection at a dosage of 37 MBq. Taking advantage of the ACE2-mediated interaction and natural trigger mechanism of virus-induced endocytosis, 99mTc-MV represents a theranostic biosensor of Auger electrons that can expose viral RNA to lethal amounts of radiation, with the host cells receiving no detrimental radiation.
Transarterial radioembolization (TARE) is a primary palliative treatment for advanced liver cancer. Nonetheless, its therapeutic efficacy is frequently hindered by resistance to tumor cell apoptosis induced by inter-radiotherapy. Induction of multiple cell death modalities provides a potential solution to this challenge. Ferroptosis, a distinct form of cell death from apoptosis, is dependent on the intracellular Fe2+-mediated Fenton reaction for the production of hydroxyl radicals (·OH) and is gaining recognition as a promising approach for cancer treatment. In this study, we synthesized a therapeutic radionuclide iodine-131 (131I)-based TARE agent by combining 131I-labeled iron-based MIL-88B(Fe) nanoparticles (NPs) (abbreviated as 131I-MIL-88B(Fe)) with Lipiodol to achieve a combined apoptosis-ferroptosis tumor therapy. Specifically, a mixture of Lipiodol and 131I-MIL-88B(Fe) NPs was injected into the liver tumors through the hepatic artery. Lipiodol blocks the arterial blood supply of the tumor, causing tumor tissue necrosis, whereas 131I inter-radiotherapy damages deoxyribonucleic acid (DNA) through direct action or indirectly via the production of ·OH through H2O radiolysis, leading to tumor cell apoptosis. Importantly, hydrated electrons (eaq-), a byproduct of H2O radiolysis, promoted the conversion of Fe3+ to Fe2+ in MIL-88B(Fe) NPs, enhancing the efficacy of the Fenton reaction and triggering ferroptosis. In vitro experiments demonstrated that compared to 131I alone, 131I-MIL-88B(Fe) NPs significantly enhanced ferroptosis-mediated tumor cell death due to 131I-induced Fe2+ production, which increased catalytic activity in the Fenton reaction. In a rat model bearing orthotopic N1S1 liver tumors, TARE with Lipiodol and 131I-MIL-88B(Fe) NPs induced tumor cell necrosis, apoptosis, and ferroptosis, resulting in improved therapeutic outcomes. This study leverages eaq- to facilitate Fe3+/Fe2+ conversion for efficient ferroptosis, turning waste into a valuable resource. This demonstrated the innovative integration of multiple treatment strategies to augment the efficacy of TARE in liver cancer therapy.
A 68-year-old man with rising PSA (0.363 ng/mL) 6 years post-prostatectomy underwent 18 F-PSMA-1007 PET/CT. The scan revealed rib metastasis and an unexpected PSMA-avid focus in the ascending colon. Previous 68 Ga-PSMA and subsequent 18 F-FDG PET both showed no abnormal uptake in the ascending colon area. Colonoscopy confirmed an ascending colon diverticulum. This rare case demonstrates intense 18 F-PSMA-1007 uptake in a colonic diverticulum, likely attributable to PSMA expression by neovascular endothelium or inflammatory cells. Clinicians should consider colonic diverticulum in the differential diagnosis of PSMA-avid colonic lesions to prevent misdiagnosis.
A 68-year-old man with rising PSA (0.363 ng/mL) 6 years post-prostatectomy underwent 18 F-PSMA-1007 PET/CT. The scan revealed rib metastasis and an unexpected PSMA-avid focus in the ascending colon. Previous 68 Ga-PSMA and subsequent 18 F-FDG PET both showed no abnormal uptake in the ascending colon area. Colonoscopy confirmed an ascending colon diverticulum. This rare case demonstrates intense 18 F-PSMA-1007 uptake in a colonic diverticulum, likely attributable to PSMA expression by neovascular endothelium or inflammatory cells. Clinicians should consider colonic diverticulum in the differential diagnosis of PSMA-avid colonic lesions to prevent misdiagnosis.
A 50-year-old woman presented with persistent left hip pain. MRI suggested metastatic lesions or hematologic disease. Further evaluation with 68Ga-FAPI-04 PET/CT revealed multiple skeletal lesions with radiotracer uptake and a non-avid low-density mass in the right parathyroid area. Elevated parathyroid hormone, hypercalcemia, and a 99mTc-sestamibi-avid right parathyroid mass led to a diagnosis of right parathyroid adenoma causing secondary brown tumors. Surgical removal of the parathyroid mass confirmed the diagnosis, highlighting the efficacy of 68Ga-FAPI-04 PET imaging in detecting brown tumors.
Extracellular vesicles (EVs) have shown great potential for treating various diseases. Translating EVs-based therapy from bench to bedside remains challenging due to inefficient delivery of EVs to the injured area and lack of techniques to visualize the entire targeting process. Here we developed a dopamine surface functionalization platform that facilitates easy and simultaneous conjugation of targeting peptide and multi-mode imaging probes to the surface of EVs. Utilizing this platform we concurrently modified M2 microglia-derived EVs (M2-EVs) with neuronal targeting peptide rabies virus glycoprotein peptide 29 (RVG29) and multi-modal imaging tracers, resulting in the targeted delivery of M2-EVs to stroke mice brain and enabled the dynamic visualization of the targeting process from whole-body to cellular levels. We determined that intra-arterial injection achieved the highest efficiency of targeted delivery of engineered EVs to the stroke mice brain, improved therapeutic efficacy by reducing neuronal apoptosis. Mechanistically, EVs miRNA array revealed that a number of anti-apoptosis related miRNAs were significantly up-regulated, including miR-221-3p and miR-423-3p, both exerted anti-apoptotic effects through p38/ERK signalling pathways in stroke. Overall, this platform provides a facile and powerful tool for multifunctional engineering of EVs for multiscale therapeutic evaluation and enhancement of EV-based therapy, with valuable prospects for clinical translation.