Molecular imaging of HER2 expression in breast cancer patients using a novel peptide-based tracer 99mTc-HP-Ark2: a pilot study.

BACKGROUND: Due to the temporal and spatial heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in breast tumors, immunohistochemistry (IHC) cannot accurately reflect the HER2 status in real time, which may cause misguided treatment decisions. HER2-specific imaging can noninvasively determine HER2 status in primary and metastatic tumors. In this study, HER2 expression in breast cancer patients was determined in vivo by SPECT/CT of 99mTc-HP-Ark2, comparing with PET/CT of 18F-FDG lesion by lesion. METHODS: A novel HER2-targeted peptide probe 99mTc-HP-Ark2 was constructed. Biodistribution and nanoScan SPECT/CT imaging were performed in mice models. The correlation between the quantified tumor uptake and HER2 expression in tumor cells was analyzed. In the pilot clinical study, a total of 34 breast cancer patients (mean age ± SD: 49 ± 10 y) suspected of having breast cancer according to mammography or ultrasonography were recruited at Peking Union Medical College Hospital, and 99mTc-HP-Ark2 SPECT/CT and 18F-FDG PET/CT were carried out with IHC and fluorescence in situ hybridization as validation. RESULTS: Small animal SPECT/CT of 99mTc-HP-Ark2 clearly identified tumors with different HER2 expression. The quantified tumor uptake and tumor HER2 expression showed a significant linear correlation (r = 0.932, P < 0.01). Among the 36 primary lesions in the 34 patients, when IHC (2 +) or IHC (3 +) was used as the positive evaluation criterion, 99mTc-HP-Ark2 SPECT/CT imaging with a tumor-to-background ratio of 1.44 as the cutoff value reflected the HER2 status with sensitivity of 89.5% (17/19), specificity of 88.2% (15/17) and accuracy of 88.9% (32/36), while the 18F-FDG PET/CT showed sensitivity of 78.9% (15/19), specificity of 70.6% (12/17) and accuracy of 75.0% (27/36). In particular, 100% of IHC (3 +) tumors were all identified by 99mTc-HP-Ark2 SPECT/CT imaging. CONCLUSION: 99mTc-HP-Ark2 SPECT/CT can provide a specific, noninvasive evaluation of HER2 expression in breast cancer, showing great potential to guide HER2-targeted therapies in clinical practice. CLINICALTRIALS: gov Trial registration: NCT04267900. Registered 11th February 2020. Retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/results?pg=1&load=cart&id=NCT04267900 .

Meta-analysis of Influencing Factors of 18F-Fluorodeoxyglucose Uptake of Brown Adipose Tissue in PET/CT Imaging.

Objective To explore the influencing factors of 18F-Fluorodeoxyglucose(18F-FDG) uptake of brown adipose tissue(BAT) in PET/CT imaging by performing meta-analysis.Methods Relevant articles published between 1980 and 2016 were searched in PubMed,EMBASE,Web of Science,CBM,WanFang Data,CNKI,and VIP.The factors of gender,season and age were extracted according to the inclusive criteria.Meta-analysis was performed to analyze the factors.Results The merger OR value and 95% CI of 18F-FDG uptake of BAT with gender,age,season were 2.67 (2.30-3.11),2.17 (1.38-3.39),and 15.35 (4.72-49.95) respectively.The 18F-FDG uptake rate of BAT was 2.16 times in females as that in males,8.67 times in the minors as that in the adults,and 1.94 times in winter as that in summer.Conclusion Gender,season,and age are risk factors for 18F-FDG uptake of BAT.

A Rare Case of Follicular Dendritic Cell Tumor of the Abdominal Cavity Visualized by 18F-AlF-NOTA-Octreotide PET/CT.

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. 18F-AlF-NOTA-octreotide PET/CT was performed for staging. 18F-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.

Al18F-NOTA-Octreotide PET/CT and 18F-FDG PET/CT for Detecting Cerebellar Hemangioblastoma in a Patient With Von Hippel-Lindau Disease.

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.

Diagnostic performance and clinical impact of 18F-AlF-NOTA-octreotide in a large cohort of patients with neuroendocrine neoplasms: A prospective single-center study.

Purpose: Somatostatin receptor imaging with 18F-AlF-NOTA-octreotide (18F-AlF-OC) has shown promising performance in neuroendocrine neoplasms (NENs). In this study, we aim to investigate the diagnostic performance and clinical impact of 18F-AlF-OC in a large prospective cohort of patients with NEN. Methods: Between January 2023 and November 2023, a total of 219 patients with confirmed or suspected NEN were enrolled prospectively and underwent 18F-AlF-OC PET/CT at 2 h post-injection. The primary endpoint was the diagnostic performance, including sensitivity, specificity, and accuracy. An additional primary endpoint was the impact of 18F-AlF-OC on clinical management. The reference standard was based on the results of histopathology or radiological follow-up. Results: 205 patients were included in the final analysis. The patient-level sensitivity, specificity, and accuracy of 18F-AlF-OC PET/CT compared with contrast-enhanced CT/MRI were 90.5% vs. 81.8%, 93.1% vs. 71.1%, and 91.2% vs. 79.4%, respectively. 26 patients had tiny gastrointestinal NENs (smaller than 1 cm in diameter). The patient-based sensitivity of 18F-AlF-OC PET/CT and contrast-enhanced CT/MRI were 61.5% (16/26) and 37.5% (9/24), respectively. The smallest diameter of gastrointestinal NEN detected by 18F-AlF-OC PET/CT was 0.6 cm in the rectum, 0.3 cm in the stomach, and 0.5 cm in the duodenum. 18F-AlF-OC PET/CT results led to changes in clinical management in 19.5% of patients (40/205), owing mainly to new or unexpected findings compared to contrast-enhanced CT/MRI. Conclusion: 18F-AlF-OC PET/CT demonstrated great diagnostic performance in patients with NEN, particularly for detecting tiny gastrointestinal NEN. Furthermore, 18F-AlF-OC PET/CT impacted the therapeutic management in 19.5% of patients. Our results further validate the role of 18F-AlF-OC as a somatostatin receptor imaging tracer in clinical practice.

The Isolated Humeral Metastasis as the Initial Presentation of Renal Cell Carcinoma Revealed by 18 F-FDG PET/CT.

ABSTRACT: Renal cell carcinoma (RCC) with isolated humeral metastasis as the initial presentation is rare. We reported FDG PET/CT findings of isolated humeral metastasis from RCC in a 63-year-old man with right upper arm pain as the initial presentation. The bone scanning in an outside hospital showed that the focus with increased uptake of the right humerus was possibly malignant. FDG PET/CT showed that the right humeral mass had intense activity, and there was an additional FDG lesion in the lower pole of the right kidney. The mass of the right humerus was later confirmed as humeral metastasis from RCC by pathological examination.

Ovarian Metastasis From Diffuse Epithelioid Malignant Mesothelioma Revealed by 18 F-FDG PET/CT.

ABSTRACT: Diffuse epithelioid malignant mesothelioma (MM) with metastasis to the ovary is rare. We reported FDG PET/CT findings in a 39-year-old woman with ovarian metastasis from diffuse epithelioid MM. The ultrasound findings at the external hospital revealed multiple masses in the hepatic hilus. FDG PET/CT examination was recommended to evaluate the nature of the lesions. It showed that 2 hypodense lesions in the perihepatic space had intense activity, and there was an additional FDG lesion in the right ovary, which was later confirmed as diffuse epithelioid MM with ovarian metastasis by pathological examination.

The Humeral Metastasis as the Initial Presentation of Lung Adenocarcinoma Revealed by 18F-FDG PET/CT.

ABSTRACT: Lung adenocarcinoma with humeral metastasis as the initial presentation is rare. We reported FDG PET/CT findings of solitary humeral metastasis from adenocarcinoma of the lung in a 57-year-old man with the right upper arm pain as the initial presentation. MRI showed bone destruction of the right humerus with a soft tissue mass, suggesting the possibility of malignancy. FDG PET/CT showed that the right humeral mass had strong activity, and there were additional FDG lesions in the right armpit, left apical lung, and left adrenal gland, which was later confirmed as humeral metastasis from lung adenocarcinoma by pathological examination.

Prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in esophageal high-grade neuroendocrine carcinoma: A bicenter retrospective study.

Objective: The aim of this bicentric retrospective study was to assess the prognostic value of 18F-FDG PET/CT in patients with esophageal high-grade neuroendocrine carcinoma (NECs). Methods: From the database of two centers, 28 patients affected by esophageal high-grade NECs who underwent 18F-FDG PET/CT before treatment were retrospectively reviewed. Metabolic parameters (SUVmax, SUVmean, tumor-to-blood-pool SUV ratio (TBR), tumor-to-liver SUV ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG)) of the primary tumor were measured. Univariate and multivariate analyses were performed for progression-free survival (PFS) and overall survival (OS). Results: After a median follow-up period of 22 months, disease progression occurred in 11 (39.3%) patients, and death occurred in 8 (28.6%) patients. The median PFS was 34 months, and the median OS was not reached. Univariate analyses revealed that among metabolic parameters, only MTV and TLG were significant prognostic factors, while among clinical variables, only distant metastasis was a significant factor for both PFS and OS (P< 0.05). On multivariate analyses, MTV and TLG were independent prognostic factors for both PFS and OS (P< 0.05). Conclusions: In patients with esophageal high-grade NEC, MTV and TLG measured on pretreatment 18F-FDG PET/CT are independently prognostic factors for predicting PFS and OS, and might be used as quantitative prognostic imaging biomarkers.

Comparison of 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT in Patients With SAPHO Syndrome.

PATIENTS AND METHODS: 68Ga-DOTA-FAPI-04 PET/CT was performed on a cohort of 21 patients with known SAPHO syndrome. All patients underwent 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT on 2 consecutive days. The positive rates of the PET/CT scans at the sites of the osteoarticular symptom, the uptake values, and agreement with clinical osteoarticular symptom were compared. RESULTS: A total of 38 sites of involvement were detected. 18F-FDG PET/CT revealed 28 lesions. In contrast, 68Ga-DOTA-FAPI-04 PET/CT detected not only all lesions shown on 18F-FDG PET/CT but additional 10 lesions. 68Ga-DOTA-FAPI-04 scan also demonstrated significantly higher uptake and target-to-background ratio than 18F-FDG studies in the skeletal involvements. The agreement between 68Ga-DOTA-FAPI-04-positive lesions and current osteoarticular lesions was substantial (κ = 0.79, P < 0.001), whereas 18F-FDG had low to moderate agreement with clinical symptoms (κ = 0.52, P < 0.001). CONCLUSIONS: 68Ga-DOTA-FAPI-04 has potential as a promising imaging agent for the evaluation of SAPHO syndrome.

Similar Findings on 18F-MFBG PET/CT and 68Ga-DOTATATE PET/CT in a Patient With Widespread Metastatic Pheochromocytoma.

ABSTRACT: A 27-year-old woman with known malignant pheochromocytoma was enrolled in a clinical trial to compare efficacy of 68Ga-DOTATATE PET/CT and 18F-MFBG PET/CT. Images from both studies detected similar number of the metastatic lesions. In addition, both studies detected more lesions than 131I-MIBG imaging.

Site-based performance of 131I-MIBG imaging and 99mTc-HYNIC-TOC scintigraphy in the detection of nonmetastatic extra-adrenal paraganglioma.

OBJECTIVES: This study aimed to evaluate the performance of 131I-metaiodobenzylguanidine (MIBG) imaging to detect nonmetastatic extra-adrenal paragangliomas at their respective sites (abdominal vs. thoracic vs. head and neck vs. urinary bladder), and compare it with that of 99mTc-hydrazinonicotinyl-tyr3-octreotide (HYNIC-TOC) scintigraphy. METHODS: We retrospectively analyzed 235 patients with nonmetastatic extra-adrenal paragangliomas who underwent preoperative 131I-MIBG imaging or 99mTc-HYNIC-TOC scintigraphy. Of all 235 patients, 145 patients underwent both imaging procedures, 16 patients 131I-MIBG imaging only and 74 patients 99mTc-HYNIC-TOC scintigraphy only. RESULTS: The overall sensitivity of 131I-MIBG and 99mTc-HYNIC-TOC imaging to detect extra-adrenal paragangliomas regardless of tumor sites was 75.8% (122/161) and 67.6% (148/219), respectively (P = 0.082). However, when stratified by tumor sites, 131I-MIBG imaging showed a significant improvement in the detection of extra-adrenal abdominal paragangliomas with a sensitivity of 90.3% (103/114), which was significantly higher than that of 99mTc-HYNIC-TOC scintigraphy (67.6% (96/142); P = 0.000). In addition, the intensity of tracer uptake in the extra-adrenal abdominal paragangliomas with 131I-MIBG imaging was evidently higher than with 99mTc-HYNIC-TOC scintigraphy. The sensitivity of 131I-MIBG imaging and 99mTc-HYNIC-TOC scintigraphy to detect urinary bladder, head and neck, and thoracic paragangliomas were 18.7 vs. 18.5% (P = 1.000); 17.4% vs. 84.6% (P = 0.000) and 60% vs. 94.4% (P = 0.030), respectively. CONCLUSIONS: 131I-MIBG imaging could become the first-line investigation modality in patients with extra-adrenal abdominal paragangliomas. However, 99mTc-HYNIC-TOC scintigraphy has high sensitivity and is superior to 131I-MIBG imaging for detecting head & neck and thoracic paraganglioma. Both 131I-MIBG imaging and 99mTc-HYNIC-TOC scintigraphy have poor performance for detecting urinary bladder paragangliomas.

Head-to-Head Comparison of 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 PET/CT in Patients With Tumor-Induced Osteomalacia: A Prospective Study.

Background: The purpose of this study is to compare the sensitivity of 68Ga-DOTA-JR11 and 68Ga-DOTA-TATE PET/CT for detecting the responsible tumor of tumor-induced osteomalacia (TIO) and investigate if 68Ga-DOTA-JR11 PET/CT can identify the culprit tumor of TIO in multiple suspicious lesions in 68Ga-DOTA-TATE PET/CT. Methods: A total of 19 patients with suspected TIO were prospectively recruited in this study. Each patient underwent whole-body PET/CT scan 40-60 min postinjection using 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 on the same PET/CT, respectively in sequence, and on consecutive days. The diagnosis of TIO was confirmed by the combination of the postsurgical pathological results of the tumor and clinical information. Results: Among the 19 patients with TIO who were included in this study, culprit tumors from all patients were confirmed pathologically. 68Ga-DOTA-TATE PET/CT positively identified the causative tumor in 18/19 patients, whereas 68Ga-DOTA-JR11 PET/CT was positive in 11/19 patients (94.7% vs. 57.9%, respectively; p < 0.05). 68Ga-DOTA-TATE PET/CT demonstrated more than one increased focal activity in 7 patients for a total of 16 lesions (3 lesions each in 2 patients and 2 lesions each in the rest 5 patients). However, seven of these 16 lesions showed concordant results on 68Ga-DOTA-JR11 PET/CT by demonstrating increased activity (one lesion in each of the 7 patients). The surgical specimens of the lesions in these 7 patients confirmed the phosphaturic mesenchymal tumor. A total of 11 culprit tumors were positive in both 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 PET/CT. The SUVmax of 11 culprit tumors was significantly higher on 68Ga-DOTA-TATE PET/CT compared with that on 68Ga-DOTA-JR11 PET/CT (17.8 ± 12.5 vs. 6.8 ± 6.2; p < 0.05). Conclusions: 68Ga-DOTA-TATE PET/CT is more sensitive to 68Ga-DOTA-JR11 PET/CT in the detection of the culprit tumor of TIO. However, 68Ga-DOTA-JR11 PET/CT might be helpful to identify the tumor in multiple suspicious lesions in 68Ga-DOTA-TATE PET/CT. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04689893.

Use of 18F-FDG PET/CT to Differentiate Ectopic Adrenocorticotropic Hormone-Secreting Lung Tumors From Tumor-Like Pulmonary Infections in Patients With Ectopic Cushing Syndrome.

BACKGROUND: Ectopic adrenocorticotropic hormone (ACTH)-secreting lung tumors represent the most common cause of ectopic Cushing syndrome (ECS). Pulmonary opportunistic infections are associated with ECS. The present study aimed to evaluate the usefulness of 18F-FDG PET/CT for differentiating ectopic ACTH-secreting lung tumors from tumor-like pulmonary infections in patients with ECS. METHODS: We retrospectively reviewed the imaging data of 24 patients with ECS who were suspected to have ACTH-secreting lung tumors and underwent 18F-FDG PET/CT between 2008 and 2019. Eleven patients with lung tumors and 4 with pulmonary infections also had additional somatostatin receptor imaging (99mTc-HYNIC-TOC SPECT/CT or 68Ga-DOTATATE PET/CT). RESULTS: In total, 18 patients had lung tumors and six had pulmonary infections. The primary source of ECS remained occult in the six patients with pulmonary infections. The maximum standardized uptake value (SUVmax) for pulmonary infections was significantly higher than that for tumors (P = 0.008). Receiver operating characteristic analysis revealed that a cut-off SUVmax of 4.95 helped in differentiating ACTH-secreting lung tumors from infections with 75% sensitivity and 94.4% specificity. For the 11 patients with ACTH-lung tumors, somatostatin receptor imaging (SRI) was positive in 6; while for the 4 with pulmonary infections, SRI was positive in 2. The sensitivity and specificity of somatostatin receptor imaging (SRI) for detecting ACTH-secreting lung tumor was 54.5% and 50%. CONCLUSIONS: Our findings suggest that pulmonary infections exhibit significantly higher FDG uptake than ACTH-secreting lung tumors in 18F-FDG PET/CT. An SUVmax cut-off value of 4.95 may be useful for differentiating the two conditions. Our results also suggested that SRI may not be an effective tool for differentiating the two conditions given the relatively low specificity.

Diagnostic and prognostic value of FDG PET-CT in patients with suspected recurrent thymic epithelial tumors.

This study aimed to evaluate the diagnostic and prognostic value of FDG PET/CT in patients with suspected recurrent thymic epithelial tumors (TETs). We retrospectively reviewed 83 patients with histopathologically proven TETs (50 thymomas; 33 thymic carcinomas) who underwent FDG PET/CT after surgery. The sensitivity and specificity of FDG PET/CT in detecting recurrence were calculated. The progression-free survival rate (PFS) was calculated by the Kaplan-Meier method. FDG PET/CT results were positive in 50 patients and negative in 33. Recurrent TETs were confirmed in 40 of 50 patients with positive PET/CT findings. The sensitivity and specificity of FDG PET/CT were 100% and 76.7%, respectively. Disease progression occurred in 28 patients during the follow-up. FDG PET/CT showed added prognostic value over the Masaoka stage and histopathology. Among patients with the same Masaoka stage, negative PET/CT was significantly associated with better PFS (P < 0.001). Similarly, among patients with the same histopathology, negative PET/CT was also associated with a significantly longer PFS (P < 0.001). FDG PET/CT demonstrated a good diagnostic performance in patients with recurrent TETs and had an important prognostic value in assessing the risk of disease progression.

Hypermetabolic Unicentric Castleman Disease of Kidney on FDG PET/CT.

ABSTRACT: A 62-year-old man presented with a huge lesion of left kidney on ultrasound in a health examination 1 month ago. The mass showed hypervascularity on enhanced CT and intense FDG uptake on FDG PET/CT in the lower pole of kidney, which suggested renal malignancy. The histopathological result after surgical resection of the mass confirmed the diagnosis of Castleman disease, the hyaline vascular variant.

Hypermetabolic Cerebral Metastases of Cardiac Myxoma on FDG PET/CT.

ABSTRACT: A 66-year-old woman with a history of surgical resection of left atrial myxoma 6 months ago presented with multiple brain lesions with MRI. An FDG PET/CT was performed for further evaluation. The images showed that cerebral tumors had variable and increased FDG uptake in general, and no other abnormal FDG-avid lesions were noted. The tumor of right occipital lobe was resected and confirmed as metastatic cardiac myxoma on histology.