Objective:Early detection of synergistic cardiotoxicity induced by sequential anthracycline and programmed cell death protein 1(PD-1)inhibitor therapy remains challenging because conventional assessments identify late-stage functional impairment.This study aimed to determine the sensitive imaging probe for early therapy-associated cardiotoxicity and validate findings using integrated positron emission tomography/magnetic resonance imaging(PET/MRI). Methods:Cardiotoxicity was assessed in mouse models treated with PD-1 inhibitor or sequential doxorubicin(DOX)and PD-1 inhibitor therapy.Serial biodistribution analyses of 18F-fluorodeoxyglucose(18F-FDG),18F-fibroblast activation protein inhibitor(18F-FAPI),99mTc-methoxyisobutylisonitrile(99mTc-MIBI),and 11C-acetate were performed.Histopathological evaluation assessed inflammation,mitochondrial injury,and fibrosis.Findings were validated in a prospective lymphoma cohort receiving sequential anthracycline and PD-1 inhibitor therapy using integrated 18F-FDG PET/MRI.Myocardial maximum standardized uptake value(SUVmax),strain parameters,tissue mapping indices,and electrocardiographic(ECG)changes were analyzed. Results:Sequential DOX and PD-1 inhibitor therapy induced an early increase in myocardial 18F-FDG uptake in mice before preceding systolic dysfunction.Histopathological examination confirmed inflammatory cell infiltration and mitochondrial swelling without extracellular matrix remodeling.In contrast,uptake of 18F-FAPI,99mTc-MIBI,and 11C-acetate remained unchanged.In patients with lymphoma,myocardial SUVmax was significantly higher in patients with ECG abnormalities[ECG(+)]than in those without ECG abnormalities[ECG(-)],whereas global longitudinal strain,global radial strain,and global circumferential strain were significantly reduced(all P<0.05).After the third PD-1 cycle,myocardial SUVmax remained elevated in ECG(+)patients,whereas strain parameters declined after 5-6 cycles,suggesting that metabolic alterations precede functional impairment.SUVmax_heart demonstrated the highest diagnostic accuracy for cardiotoxicity[cutoff=3.0;area under the curve(AUC)=0.873;sensitivity=93.3%;specificity=80.0%]. Conclusions:Cardiac 18F-FDG PET/MRI enables early detection of synergistic cardiotoxicity induced by DOX and PD-1 inhibitors before structural or functional deterioration occurs.SUVmax_heart may serve as an imaging biomarker for risk stratification and timely cardioprotective intervention.
To develop an anthropomorphic phantom that enables the simultaneous evaluation of key performance metrics for nuclear medicine imaging systems and to preliminarily validate its application in PET/CT. The anthropomorphic phantom replicates thoracic and abdominal anatomy, simulating human skeletal structures, lung tissue, soft tissue, and tumors. The phantom is divided into five functional regions: a lung tumor detection region (right lung with spheres), an attenuation and scatter correction assessment region with a non-radioactive compartment (left lung), an abdominal tumor detection region (right abdomen with spheres), a uniform background region (left abdomen), and a spatial resolution assessment region incorporating line sources, centered along the mid-sagittal plane traversing the thoracoabdominal extent. All phantom imaging was performed on a Discovery MI (GE Healthcare) PET/CT scanner using sphere-to-background ratios (SBRs) of approximately 4, 6, 8, and 10, and line-to-background ratios (LBRs) of approximately 200, 500, 1000, and 2000. Spatial resolution was measured using a two-point-source method, including visual assessment and valley-to-peak ratio (VPR) analysis, and a single-point-source method. Lesion detectability was assessed visually and by contrast-to-noise ratio (CNR). Signal-to-noise ratio (SNR), quantitative accuracy (percentage error, PE), image uniformity (IU), and residual error (RE) for attenuation and scatter correction were measured. Additionally, a matched SBR comparison was performed using the NEMA image quality (IQ) phantom. As LBR increased from 200 to 2000, the single-point-source spatial resolution improved from approximately 7 mm to 3 mm, whereas the visually determined two-point-source results remained nearly constant around 6 mm. At the fixed 7-mm spacing, VPR decreased with increasing LBR, indicating improved profile separation between adjacent point sources. The 3 mm sphere was detectable in the lung and abdomen at SBRs of ≥ 6 and 10, respectively. For SBRs set to approximately 4, 6, 8, and 10, SNRs measured in the left abdominal uniform region were 20.50, 25.47, 25.19 and 25.75; PE, axial IU, and RE were all < 5
BACKGROUND:To investigate the prognostic and treatment values of maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) in early-stage extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL). METHODS:MTV and SUVmax of the primary tumor in 122 patients with early-stage ENKTCL were measured. The prognostic capacity of MTV and SUVmax and their implications for treatment selection were evaluated. Potential mechanisms of MTV and SUVmax were evaluated through transcriptome analysis of tumors in 16 patients. RESULTS:Patients with high-SUVmax or large-MTV were more likely to have adverse clinical factors. Both SUVmax and MTV were associated with overall survival (OS) in univariate analysis (P = 0.029 and 0.001, respectively). MTV was independently associated with OS (P = 0.027), and mediation analysis suggested that distant metastasis statistically accounted for 98.2% of this association. In the intermediate- and high-risk early-stage subgroup, patients with MTV < 50 mL had significantly better OS and progression-free survival (PFS) (both P = 0.002) than those with MTV ≥ 50 mL, but showed survival outcomes comparable to low-risk early-stage patients. Furthermore, radiotherapy and combined-modality therapy (CMT) yielded comparable PFS (P = 0.268) and OS (P = 0.570) in patients with MTV < 50 mL. In contrast, for patients with MTV ≥ 50 mL, CMT resulted in better PFS and OS (both P < 0.001) compared to RT alone. CONCLUSION:MTV is an independent metabolic predictor of survival and may identify patients who are more likely to benefit from CMT in early-stage ENKTCL. Further prospective validation is warranted.
BACKGROUND:Accurate diagnosis and staging are crucial for the management of patients with hepatobiliary malignancies. Here, we investigated the efficacy of Al 18 F-NOTA-FAPI-74 PET/CT in detecting hepatobiliary malignancies and compared the results with 18 F-FDG PET/CT. PATIENTS AND METHODS:Participants with hepatobiliary malignancies were prospectively enrolled and underwent paired Al 18 F-NOTA-FAPI-74 and 18 F-FDG PET/CT from April 2023 to March 2024. Histopathology and/or follow-up imaging served as the reference standard. The SUVmax of the primary and metastatic lesions between Al 18 F-NOTA-FAPI-74 and 18 F-FDG PET/CT were compared using the Wilcoxon signed-rank test. The association between Al 18 F-NOTA-FAPI-74 uptake intensity and immunohistochemical FAP expression was analyzed with Spearman r correlation. RESULTS:Our cohort comprised of 28 patients with hepatobiliary malignancies, including 12 with hepatocellular carcinoma, 13 with intrahepatic cholangiocarcinoma (ICC), 2 with perihilar cholangiocarcinoma, and 1 with gallbladder carcinoma. Of these 28 patients, 13 underwent PET/CT for initial staging and 15 for restaging. Al 18 F-NOTA-FAPI-74 PET/CT showed higher sensitivity than 18 F-FDG PET/CT for detecting primary tumors [100% (13/13) vs 92.3% (12/13)], lymph node metastases [79.2% (42/53) vs 54.7% (29/53)], and bone and visceral metastases [97.6% (164/168) vs 69.0% (116/168)]. Al 18 F-NOTA-FAPI-74 PET/CT findings led to upstaging or restaging in 6 of 28 patients compared with the 18 F-FDG PET/CT-based stage. In addition, Al 18 F-NOTA-FAPI-74 PET/CT detected tumor-related obstructive inflammation in 7 patients, while 18 F-FDG PET/CT detected it in only 1 patient (25% vs 3.6%). All these 7 patients suffered from cholangiocarcinomas, including 5 with ICC and 2 with perihilar cholangiocarcinomas. The SUVmax of obstructive inflammation on Al 18 F-NOTA-FAPI-74 PET/CT was significantly lower than that of tumor (median SUVmax, 4.0 vs 8.8; P = 0.008). A positive correlation was found between FAPI uptake and FAP expression ( r = 0.730, P = 0.04). CONCLUSIONS:In patients with hepatobiliary malignancies, Al 18 F-NOTA-FAPI-74 PET/CT outperformed 18 F-FDG PET/CT in detecting primary tumors and metastatic lesions, resulting in more accurate staging or restaging. In addition, Al 18 F-NOTA-FAPI-74 PET/CT showed good detection efficacy for tumor-related obstructive inflammation, which was only found in cholangiocarcinoma, thus rendering Al 18 F-NOTA-FAPI-74 the potential to differentiate ICC from hepatocellular carcinoma.
Aim: Recent studies have demonstrated the potential of PET/CT with 18F-labeled ligands targeting prostate-specific membrane antigen (PSMA), as a promising method for prostate cancer (PCa) management. The aim of this study is to assess the clinical value of [18F]AlF-Thretide ([18F]AlF-PSMA-BCH) PET/CT and early time-point PET acquisition for detecting and staging PCa. Materials and Methods: From November 2022 to May 2023, a total of 73 PCa patients were included in our study. Along with whole-body PET/CT conducted at a median time of 76 min (range: 59-139 min) post-injection, a single-bed pelvic early PET/CT scan was performed, starting at a median time of 187 s (range: 161-453 s) post-injection. Visual analysis of the images was performed first, followed by semiquantitative analysis of maximum standardized uptake value (SUVmax) of primary PCa lesions, metastases, bladder, and surrounding tissues on both early and routine time-point PET/CT scans. Results: Among 56 non-surgical patients (either treatment-naive or after androgen deprivation therapy only) who had previously undergone conventional imaging, N staging was revised in 4 cases, and M staging in 2 cases. In 54 patients with bone scans for comparison, 111 lesions on [18F]AlF-Thretide PET/CT and 41 lesions on bone scans were identified as indicative of bone metastases. The median tumor-to-bladder (T/BL) ratios for primary lesions increased from 0.33 (range: 0.03-6.22) on routine time-point PET/CT to 4.66 (range: 0.24-645.00) on early time-point PET/CT. In 94.6% (53/56) of patients, the T/BL ratios were higher on early PET/CT scans than on routine time-point PET/CT scans. However, the SUVmax of surrounding tissues was found to be higher on early PET/CT scans compared to routine PET/CT scans (external iliac vessels: 8.02 ± 1.64 vs. 2.66 ± 0.59; inferior vesical artery branches near the prostate: 4.70 ± 1.09 vs. 2.30 ± 0.49; gluteus maximus muscle: 1.19 ± 0.31 vs. 0.80 ± 0.25). Of the 17 patients who underwent surgery prior to PET/CT, early PET/CT scans improved the detection rate of local recurrences from 2/17 to 5/17. Conclusion: [18F]AlF-Thretide PET/CT was shown to be a valuable imaging modality in the management of patients with PCa. Early PET/CT scans can improve the detection rate of local recurrences and provide additional information for lesions that are challenging to distinguish from urinary uptake on routine PET/CT scans.
Radiolabeled somatostatin receptor (SSTR) analogues are widely utilized for both imaging (PET or scintigraphy) and peptide receptor radionuclide therapy (PRRT) in the management of neuroendocrine neoplasms (NENs). These approaches have been extensively validated in low- to intermediate-grade gastroenteropancreatic neuroendocrine tumors (NET G1 - G2). However, data on the use of SSTR imaging - particularly SSTR PET imaging - in patients with high-grade NETs (G3) and neuroendocrine carcinomas (NECs) remain limited. This study aimed to evaluate the diagnostic performance of ¹⁸F-AlF-NOTA-octreotide (¹⁸F-AlF-OC) PET/CT in patients with high-grade NENs and assess its complementarity with ¹⁸F-FDG PET/CT. Out of 426 patients who underwent ¹⁸F-AlF-OC PET/CT between January 2023 and October 2024, 42 patients with histologically confirmed high-grade NENs (28 with G3 NETs and 14 with NECs) were retrospectively analyzed. 36 patients also underwent 18F-FDG PET/CT. Lesions were classified as positive on PET/CT if their uptake exceeded organ background activity and could not be explained by physiologic biodistribution. Tumor uptake higher than normal liver was considered high uptake. On a per-patient basis, ¹⁸F-AlF-OC PET/CT was positive in 39 of 42 patients, yielding a detection rate of 92.9
Background: Accurate diagnosis and staging are crucial for the management of patients with hepatobiliary malignancies. Here, we investigated the efficacy of Al 18 F-NOTA-FAPI-74 PET/CT in detecting hepatobiliary malignancies and compared the results with 18 F-FDG PET/CT. Patients and Methods: Participants with hepatobiliary malignancies were prospectively enrolled and underwent paired Al 18 F-NOTA-FAPI-74 and 18 F-FDG PET/CT from April 2023 to March 2024. Histopathology and/or follow-up imaging served as the reference standard. The SUVmax of the primary and metastatic lesions between Al 18 F-NOTA-FAPI-74 and 18 F-FDG PET/CT were compared using the Wilcoxon signed-rank test. The association between Al 18 F-NOTA-FAPI-74 uptake intensity and immunohistochemical FAP expression was analyzed with Spearman r correlation. Results: Our cohort comprised of 28 patients with hepatobiliary malignancies, including 12 with hepatocellular carcinoma, 13 with intrahepatic cholangiocarcinoma (ICC), 2 with perihilar cholangiocarcinoma, and 1 with gallbladder carcinoma. Of these 28 patients, 13 underwent PET/CT for initial staging and 15 for restaging. Al 18 F-NOTA-FAPI-74 PET/CT showed higher sensitivity than 18 F-FDG PET/CT for detecting primary tumors [100% (13/13) vs 92.3% (12/13)], lymph node metastases [79.2% (42/53) vs 54.7% (29/53)], and bone and visceral metastases [97.6% (164/168) vs 69.0% (116/168)]. Al 18 F-NOTA-FAPI-74 PET/CT findings led to upstaging or restaging in 6 of 28 patients compared with the 18 F-FDG PET/CT-based stage. In addition, Al 18 F-NOTA-FAPI-74 PET/CT detected tumor-related obstructive inflammation in 7 patients, while 18 F-FDG PET/CT detected it in only 1 patient (25% vs 3.6%). All these 7 patients suffered from cholangiocarcinomas, including 5 with ICC and 2 with perihilar cholangiocarcinomas. The SUVmax of obstructive inflammation on Al 18 F-NOTA-FAPI-74 PET/CT was significantly lower than that of tumor (median SUVmax, 4.0 vs 8.8; P = 0.008). A positive correlation was found between FAPI uptake and FAP expression ( r = 0.730, P = 0.04). Conclusions: In patients with hepatobiliary malignancies, Al 18 F-NOTA-FAPI-74 PET/CT outperformed 18 F-FDG PET/CT in detecting primary tumors and metastatic lesions, resulting in more accurate staging or restaging. In addition, Al 18 F-NOTA-FAPI-74 PET/CT showed good detection efficacy for tumor-related obstructive inflammation, which was only found in cholangiocarcinoma, thus rendering Al 18 F-NOTA-FAPI-74 the potential to differentiate ICC from hepatocellular carcinoma.
ABSTRACT:We present a case of 37-year-old man with multiple masses in the abdominal and pelvic cavity who underwent 18 F-AlF-NOTA-octreotide PET/CT. The masses demonstrated heterogeneously increased uptake on 18 F-AlF-NOTA-octreotide PET/CT and were suggestive of neuroendocrine tumor. However, the histopathological examinations confirmed the masses to be peritoneal mesothelioma. This case indicated that peritoneal mesothelioma should be kept in mind as one of the differential diagnoses for 18 F-AlF-NOTA-octreotide-avid tumors.
Capillary hemangiomas are commonly encountered superficially in the cutaneous, subcutaneous, or mucosal tissues during childhood and early adulthood, but retroperitoneal capillary hemangioma is a rare occurrence. We present a case of a 61-year-old woman with incidentally detected capillary hemangioma in the retroperitoneum initially presumed to be paraganglioma based on 18 F-AlF-NOTA-Octreotide PET/CT findings. Contrast-enhanced MRI revealed a hypervascular mass in the retroperitoneum. 18 F-AlF-NOTA-Octreotide PET/CT performed for suspicion of paraganglioma showed intense uptake. Histopathologic examination of the retroperitoneal mass after surgical resection confirmed the diagnosis of capillary hemangioma rather than paraganglioma.
Prostate cancer (PCa) is one of the most common malignancies among men worldwide. Early detection relies heavily on imaging accuracy, yet conventional modalities such as CT and MRI have limitations in identifying early-stage lesions. INR101 is a novel 18F-labeled PSMA-targeted PET tracer with high binding affinity, favorable biodistribution, and promising lesion detection capabilities for initial PCa diagnosis. INR101 was prepared and confirmed on radiochemical purity by HPLC to be > 93
ABSTRACT:A 13-year-old girl presented with dysphagia underwent contrast-enhanced CT and endoscopy. The CT revealed cervical esophageal wall thickening with heterogeneous enhancement. Microscopic examination of the biopsy specimen suggested a possible mesenchymal tumor. She underwent an 18 F-FDG PET/CT scan for staging. The scan showed local thickening of the cervical esophageal wall with heterogeneous and significantly elevated FDG activity. Subsequent immunohistochemical staining and fluorescence in situ hybridization confirmed the diagnosis of esophageal inflammatory myofibroblastic tumor.
A 35-year-old man with painful and difficult urination underwent 18 F-FDG and Al 18 F-Thretide PET/CT scans after a pelvic MRI suggested a prostate mass. The 18 F-FDG and Al 18 F-Thretide PET/CT scans revealed a prostate mass accompanied by an intravenous tumor thrombus. Both the prostate mass and the intravenous tumor thrombus demonstrated increased FDG uptake. Intense PSMA activity was observed in both lesions, with the intravenous tumor thrombus showing considerably higher PSMA activity compared with its FDG uptake. Histologic analysis of the biopsy confirmed the diagnosis of prostatic synovial sarcoma. PSMA immunohistochemistry showed high PSMA expression in the vascular endothelial cells within the tumor.
To investigate the risk factors of bone metastasis in lung adenocarcinoma and construct a risk prediction model. Patients with newly diagnosed primary lung adenocarcinoma admitted to our hospital between 1 March 2018 and 1 March 2023 were retrospectively enrolled as the study participants. Finally, 273 patients were included in strict accordance with the inclusion and exclusion criteria and divided into a bone metastasis group (n = 123) and a non-bone metastasis group (n = 150) according to whether bone metastasis had occurred. The clinical data of all the study participants were collected and retrospectively analysed. Bone metastases were more common in the vertebrae, ribs and hip bones, followed by the scapula, femur, sternum and skull, but they were rare in the humerus, fibula and clavicle. The bone metastasis group exhibited more clinical symptoms than the non-bone metastasis group, including the presence of primary lung adenocarcinoma > 3 cm in diameter, and the differences were statistically significant (P < 0.05). The positive rate of EGFR gene mutation and CEA, CYFRA21-1 and ALP levels in the bone metastasis group were higher than those in the non-bone metastasis group, and the differences were statistically significant (P < 0.05). Multivariate logistic regression analysis showed that positive EGFR gene mutation (P < 0.001), CEA > 5 ng/mL (P < 0.001) and primary lung adenocarcinoma diameter > 3 cm (P = 0.003) were independent risk factors for bone metastasis in lung adenocarcinoma. A receiver operating characteristic curve was used to verify the predictive value of the regression model, and the area under the curve was 0.912 (P < 0.001). The most common sites of bone metastases in newly diagnosed lung adenocarcinoma are the spine and ribs. Positive EGFR gene mutation, CEA > 5 ng/mL and primary lung adenocarcinoma diameter > 3 cm are independent risk factors for bone metastasis in lung adenocarcinoma. Not applicable.
ABSTRACT:Positivity of follicular dendritic cell tumor in somatostatin receptor imaging is rare. A 68-year-old woman underwent ultrasound in health examination. The results showed abnormal echoes in the pancreatic head region, suggestive of a neuroendocrine tumor of the pancreatic head. 18 F-AlF-NOTA-octreotide PET/CT was performed for staging. 18 F-AlF-NOTA-octreotide PET/CT revealed an irregular mass between the caudate lobe of the liver and the pancreatic head with heterogeneously increased uptake, which was later confirmed as follicular dendritic cell tumor by pathological examination.
Abstract Von Hippel-Lindau disease is a hereditary syndrome associated with various benign and malignant tumors, including hemangioblastomas. A 42-year-old man with a history of Von Hippel-Lindau disease underwent surgery for pancreatic neuroendocrine tumor and renal clear cell carcinoma and was recommended to undergo Al18F-NOTA-octreotide and 18F-FDG PETCT examination to assess potential metastases. 18F-FDG PET/CT showed low uptake in the right cerebellum, which demonstrated increased Al18F-NOTA-octreotide activity. Cerebellar mass resection surgery was performed. Pathological result was consistent with hemangioblastoma. This case report indicates the significant role of Al18F-NOTA-octreotide in the diagnosis of hemangioblastoma.
Abstract A 25-year-old woman experiencing dysphagia for 2 years underwent 18F-FDG and Al18F-FAPI-74 PET/CT. The scans showed local thickening of the cervical and upper thoracic esophageal wall with several calcifications, accompanied by increased and heterogeneous FDG uptake and more intense FAPI activity. Histopathological analysis following thoracoscopic esophagectomy confirmed the diagnosis of esophageal inflammatory pseudotumor.
Abstract A 46-year-old woman with a history of radical nephrectomy for clear cell renal cell carcinoma underwent 18F-FDG and 18F-Thretid (also known as Al18F-PSMA-BCH) PET/CT. Although the 18F-FDG PET/CT failed to detect any brain metastases, the 18F-Thretide PET/CT revealed 2 small metastases: one measuring 1.0 × 0.7 cm in the right cerebellum and the other measuring 0.4 cm in the right frontal lobe. These metastatic lesions were subsequently confirmed by brain MRI.