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J-aggregation is an efficient strategy for the development of fluorescent imaging agents in the second near-infrared window. However, the design of the second near-infrared fluorescent J-aggregates is challenging due to the lack of suitable J-aggregation dyes. Herein, we report meso -[2.2]paracyclophanyl-3,5-bis- N , N -dimethylaminostyrl BODIPY (PCP-BDP2) as an example of BODIPY dye with J-aggregation induced the second near-infrared fluorescence. PCP-BDP2 shows an emission maximum at 1010 nm in the J-aggregation state. Mechanism studies reveal that the steric and conjugation effect of the PCP group on the BODIPY play key roles in the J-aggregation behavior and photophysical properties tuning. Notably, PCP-BDP2 J-aggregates can be utilized for lymph node imaging and fluorescence-guided surgery in the nude mouse, which demonstrates their potential clinical application. This study demonstrates BODIPY dye as an alternate J-aggregation platform for developing the second near-infrared imaging agents. J-aggregation has been proved to be an efficient strategy for the development of fluorescent imaging agents in the NIR-II spectral region but the design of appropriate J-aggregates is challenging. Here, the authors demonstrate J-aggregation of a BODIPY dye with NIR-II emission and demonstrate lymph node imaging for fluorescence guided surgery.

ObjectivesTo investigate the association between CT imaging traits and texture metrics with proteomic data in patients with high-grade serous ovarian cancer (HGSOC).MethodsThis retrospective, hypothesis-generating study included 20 patients with HGSOC prior to primary cytoreductive surgery. Two readers independently assessed the contrast-enhanced computed tomography (CT) images and extracted 33 imaging traits, with a third reader adjudicating in the event of a disagreement. In addition, all sites of suspected HGSOC were manually segmented texture features which were computed from each tumor site. Three texture features that represented intra- and inter-site tumor heterogeneity were used for analysis. An integrated analysis of transcriptomic and proteomic data identified proteins with conserved expression between primary tumor sites and metastasis. Correlations between protein abundance and various CT imaging traits and texture features were assessed using the Kendall tau rank correlation coefficient and the Mann-Whitney U test, whereas the area under the receiver operating characteristic curve (AUC) was reported as a metric of the strength and the direction of the association. P values < 0.05 were considered significant.ResultsFour proteins were associated with CT-based imaging traits, with the strongest correlation observed between the CRIP2 protein and disease in the mesentery (p < 0.001, AUC = 0.05). The abundance of three proteins was associated with texture features that represented intra-and inter-site tumor heterogeneity, with the strongest negative correlation between the CKB protein and cluster dissimilarity (p = 0.047, τ = 0.326).ConclusionThis study provides the first insights into the potential associations between standard-of-care CT imaging traits and texture measures of intra- and inter-site heterogeneity, and the abundance of several proteins.Key Points• CT-based texture features of intra- and inter-site tumor heterogeneity correlate with the abundance of several proteins in patients with HGSOC.• CT imaging traits correlate with protein abundance in patients with HGSOC.

Our aim was to investigate utility of indocyanine green (ICG) and autofluorescence (AF) imaging in detection of small bowel primary and metastatic carcinoids. Using Institutional Review Board approval, ICG and AF imaging of small bowel carcinoids was performed. Imaging findings were prospectively recorded in operating room and compared with conventional imaging, surgical exploration and pathologic findings. There were 16 patients with 23 primary small bowel tumors, 27 mesenteric lymph nodes, 36 liver metastases and 2 peritoneal nodules. Carcinoid tumors exhibited brighter AF signals compared to background. AF imaging was superior to both DOTATATE PET and surgeon inspection/palpation in demonstrating small bowel primaries. Utility for metastatic lymph nodes and peritoneal metastases was limited. Superficial liver metastases exhibited brighter fluorescence compared to background on both ICG and AF imaging. This is the largest study assessing utility of near-infrared fluorescence imaging in detection of small bowel carcinoids. Our results show promise in the utilization fluorescence imaging to detect occult primary tumors and superficial liver metastases. •Autofluorescence imaging detects small bowel carcinoid tumors with a high accuracy.•Autofluorescence imaging outperforms preoperative imaging in detecting small bowel cacinoids.•Autofluorescence imaging aids in identifying occult primary tumors during surgery.•Autofluorescence imaging has a limited value in detecting lymph node metastases.•Fluorescence imaging may be used to guide resection of superficial liver metastases.

Background This study aimed to identify the yield of staging laparoscopy with peritoneal lavage cytology for gastric cancer patients and to track it over time. Methods The medical records of patients with gastric or gastroesophageal adenocarcinoma who underwent pretreatment staging laparoscopy at the authors’ institution from 1995 to 2012 were reviewed. The yield of laparoscopy was defined as the proportion of patients who had positive findings on laparoscopy, including those with macroscopic carcinomatosis, positive cytology, or other clinically important findings. To compare the yield of laparoscopy over time, the patients were divided into three 6-year ranges based on the date of diagnosis. Associations between clinicopathologic factors and peritoneal disease were examined using uni- and multivariate analyses. Results The study included 711 patients. Among these patients, 43.5 % had gastroesophageal junction tumors, 72.9 % had poorly differentiated adenocarcinoma, and 53 % had signet ring cell morphology. Endoscopic ultrasound had most commonly identified T3 (83.9 %) and N-positive (66.4 %) tumors. At laparoscopy, 148 (20.8 %) patients had been found to have macroscopic peritoneal carcinomatosis. Among 514 macroscopically negative patients who underwent peritoneal lavage cytologic analysis, 68 (13.2 %) had positive cytology results for malignancy. The total laparoscopy yield was 36 %, which did not change over time ( p = 0.58). Multivariate analysis demonstrated that positive cytology or carcinomatosis was associated with poorly differentiated histology, linitis plastica, and equivocal computed tomography findings. Conclusions Laparoscopy remains a useful staging procedure to evaluate for peritoneal spread when treatment or surgery is considered, even with the current availability of high-quality imaging.

ObjectivesTo evaluate the predictive value of CT radiomics features derived from the primary tumor in discriminating occult peritoneal metastasis (PM) in advanced gastric cancer (AGC).MethodsPreoperative CT images of 233 patients with AGC were retrospectively analyzed. The region of interest (ROI) was manually drawn along the margin of the lesion on the largest slice of venous CT images, and a total of 539 quantified features were extracted automatically. The intra-class correlation coefficient (ICC) and the absolute correlation coefficient (ACC) were calculated for selecting influential features. A multivariate logistic regression model was constructed based on the training cohort, and the testing cohort validated the reliability of the model. Additionally, another model based on the preoperative clinic-pathological features was also developed. The comparison of the diagnostic performance between the two models was performed using ROC analysis and the Akaike information criterion (AIC) value.ResultsSix radiomics features (ID_Energy, LoG(0.5)_Energy, Compactness2, Max Diameter, Orientation, and Surface Area Density) differed significantly between AGCs with and without PM and performed well in distinguishing AGCs with PM from those without PM in the primary cohort (AUC = 0.618–0.658). The radiomics model showed a higher AUC value than each single radiomics feature in the primary cohort (0.741 vs. 0.618–0.658) and similar diagnosis performance in the validation cohort. The radiomics model showed slightly worse diagnostic efficacy than the clinic-pathological model (AUC, 0.724 vs. 0.762).ConclusionVenous CT radiomics analysis based on the primary tumor provided valuable information for predicting occult PM in AGCs.Key Points• Venous CT radiomics analysis provided valuable information for predicting occult peritoneal metastases in advanced gastric cancer.• CT-based T stage was an independent predictive factor of occult peritoneal metastases in advanced gastric cancer.• A radiomics model showed slightly worse diagnostic efficacy than a clinic-pathological model.

PurposeThe aim of this study was to explore the role of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT), compared with 18F-fluorodeoxyglucose [18F]-FDG PET/CT, for evaluating peritoneal carcinomatosis in patients with various types of cancer.MethodsPatients with suspected peritoneal malignancy, who underwent both [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT between October 2019 and August 2020, were retrospectively analysed. The radiotracer uptake, peritoneal cancer index (PCI) score, and diagnostic performance of [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were evaluated and compared.ResultsOur cohort consisted of 46 patients, including 16 patients with diffuse-type peritoneal carcinomatosis, 27 with nodular-type peritoneal carcinomatosis, and 3 true-negative patients. A significant difference in standard uptake values (SUV) of lesions between [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT examination was observed (median SUV: 3.48 vs. 9.82; P < 0.001), particularly in peritoneal carcinomatosis from gastric cancer (median SUV: 3.44 vs. 8.05; P = 0.001). Moreover, [68Ga]Ga-DOTA-FAPI-04 PET/CT showed a higher PCI score and better sensitivity than [18F]-FDG PET/CT for the detection of peritoneal carcinomatosis (6 vs. 18; P < 0.001; 72.09% vs. 97.67%; P = 0.002).Conclusion[68Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated superior sensitivity over [18F]-FDG PET/CT for the detection of peritoneal carcinomatosis in patients with various types of cancer, particularly gastric cancer. Furthermore, the uptake of [68Ga]Ga-DOTA-FAPI-04 in peritoneal carcinomatosis was significantly higher than that of [18F]-FDG, demonstrating a larger extent of the lesions and yielding a higher PCI score. This could help enhance the image contrast, improve physicians’ diagnostic confidence, and reduce the proportion of missed diagnoses.

Objective To assess and compare the diagnostic performance of gallium-68-labelled fibroblast activation protein inhibitor ([ 68 Ga]FAPI-04) and fluorine-18 fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT) in gastrointestinal cancer. Methods Fifty-one patients who underwent both [ 18 F]FDG and [ 68 Ga]FAPI-04 PET/CT for initial staging or restaging were enrolled. Histopathological findings, typical radiological appearances, and clinical imaging follow-up were used as the reference standard. The diagnostic performance of the two tracers was calculated and compared. The maximum standardised uptake value (SUVmax), mean SUV (SUVmean), tumour-to-mediastinal blood pool ratio (TBR), and tumour-to-liver ratio (TLR) of primary and metastatic lesions were measured and compared between two imaging modalities. Results In patient-based analysis, [ 68 Ga]FAPI-04 showed much better diagnostic sensitivity than [ 18 F]FDG in detecting primary tumour (94.44% [17/18] vs. 61.11% [11/18]), postoperative recurrence and metastases (95.65% [22/23] vs. 69.57% [16/23]), and peritoneal carcinomatosis (100% [28/28] vs. 60.71% [17/28]) (all p < 0.05). In lesion-based analysis, [ 68 Ga]FAPI-04 showed higher sensitivity than [ 18 F]FDG for detecting lymph node metastases. In peritoneal carcinomatosis, the median SUVmax (12.12 vs. 7.18) and SUVmean (6.84 vs. 4.11) with [ 68 Ga]FAPI-04 were significantly higher than those with [ 18 F]FDG (all p < 0.005). The TBR and TLR of [ 68 Ga]FAPI-04 were significantly higher than those of [ 18 F]FDG for detecting primary tumour, lymph node, liver, and peritoneal metastases (all p < 0.005). Therapeutic management changed in 13 patients according to [ 68 Ga]FAPI-04 PET/CT compared with conventional imaging. Conclusions [ 68 Ga]FAPI-04 is superior to [ 18 F]FDG PET/CT for detecting primary tumour, postoperative recurrence and metastasis, and peritoneal carcinomatosis in gastrointestinal cancer. Key Points • [ 68 Ga]FAPI-04 PET/CT showed significantly higher sensitivity than [ 18 F]FDG PET/CT in the detection of primary tumour and postoperative recurrence and metastasis in patients with gastrointestinal carcinoma. • [ 68 Ga]FAPI-04 PET/CT had obvious advantages over [ 18 F]FDG PET/CT in the detection of peritoneal carcinomatosis from gastrointestinal carcinoma with a much higher FAPI uptake value, TBR, and TLR. • Although the median SUVmax and SUVmean of [ 68 Ga]FAPI-04 were similar to those of [ 18 F]FDG for the primary tumour, lymph node metastases, and liver metastases in gastrointestinal carcinoma, the TBR and TLR of the SUVmax and SUVmean were significantly higher on [ 68 Ga]FAPI-04 PET/CT, causing the lesions to be displayed more clearly.

ObjectiveImaging for staging ovarian cancer is important to determine the extent of disease. The primary objective of this study was to compare gated 18F-fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG PET/CT) and standard CT scan with intravenous contrast to diagnose thoracic involvement in patients with advanced ovarian cancer prior to treatment. The secondary objective was to estimate changes in the International Federation of Gynecology and Obstetrics (FIGO) stage and clinical management resulting from gated PET/CT.MethodsThe IMAGE trial is a non-randomized phase II clinical trial comparing standard CT scanning with gated PET/CT in diagnosing thoracic involvement in a non-selected group of patients with suspected ovarian cancer on a contrast CT scan. Three sets of PET images were obtained comprising an ungated 2 min whole body image, a static 7.5 min image of the upper abdomen and thorax, and a gated end-expiratory image over the upper abdomen and thorax. Images were evaluated for specificity, sensitivity, diagnostic accuracy, and the proportion of patients with changes in FIGO stage and subsequent clinical management was compared between imaging techniques.ResultsA total of 84 patients were enrolled based on a standard CT scan, 67 of whom were eligible for gated PET/CT scans. Diagnostic accuracy with gated PET/CT was more than 80% for lesions in lung, liver, extra-abdominal sites, and pleura, but less than 50% for extra-abdominal lymph nodes. Compared with CT scan at baseline, 46% of patients who had 7.5 min gated PET/CT had disease upstaged from stage III to IV, and 8% had disease downstaged from stage IV to III. However, this led to a change of management in only 5% of patients.ConclusionsGated PET/CT enables upstaging; however, in our institution it altered clinical management only in a minority of patients.Trial registration numberNCT02258165.

Objectives This study aimed to assess the utility of preoperative contrast-enhanced computed tomography (CECT) and clinical characteristics in predicting the presence and location of synchronous metastases in colon cancer (CC) patients. Methods A retrospective analysis was conducted on pathologically confirmed CC patients who underwent CECT within two weeks prior to radical resection and lymphadenectomy. Synchronous metastases were confirmed via biopsy or characteristic imaging findings. Two independent radiologists reviewed CECT features, including enhancement patterns, tumor characteristics, and lymph node status. Both univariate and multivariate logistic regression analyses were employed to evaluate the distribution of CECT features. Results The final cohort included 212 patients (95 males and 117 females, with a mean age of 64 years). Distant metastases were categorized as synchronous liver metastasis (65 patients), synchronous peritoneal metastasis (19 patients), and metastases to other sites (22 patients). Elevated carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19-9) levels, increased tumor length, higher tumor length-to-thickness ratio, presence of tumor necrosis, lymph node necrosis, and arterial-venous phase CT value differences emerged as independent predictors of synchronous metastases in CC. A predictive model, incorporating these parameters, exhibited strong predictive capability (the area under the curve (AUC) = 0.852, sensitivity: 0.802; specificity: 0.736, accuracy: 0.769). Additionally, tumor necrosis and ascites were significantly associated with synchronous peritoneal metastases, with the model demonstrating high predictive efficacy (AUC = 0.869, sensitivity: 0.895; specificity: 0.782, accuracy:0.802). Conclusions Integrating clinical characteristics with CECT imaging features provides an effective means of predicting synchronous distant metastases and their locations in CC patients, aiding in the development of personalized treatment plans that may enhance patient survival and quality of life.

Early diagnosis of peritoneal spread in malignant disease prevents unnecessary laparotomies. Minimally invasive laparoscopy with the patient under conscious sedation is a new, easily feasible diagnostic technique. This study compares prospective and controlled diagnostic minilaparoscopy with computed tomography (CT) scan for the diagnosis of peritoneal metastases. In this study, 56 patients with malignant disease were prospectively investigated with diagnostic minilaparoscopy and CT scan. The study criteria were fulfilled by 54 patients. Minilaparoscopy detected peritoneal carcinosis in 28 of 54 cases, whereas CT detected the disease in 14 of 54 cases. For 36 patients, the diagnosis could be verified by histologic examination of peritoneal biopsies or laparotomy. In this group, minilaparoscopy detected peritoneal carcinosis in 25 of 36 cases, whereas CT detected the disease in 12 of 36 cases. Minilaparoscopy was more sensitive than CT in detecting peritoneal carcinosis (100% vs 47.8%; p < 0.01). Considering its low grade of invasiveness and superior sensitivity, minilaparoscopy should be regarded as the procedure of choice for the early detection of peritoneal carcinosis.