Molecular Imaging and Biology最新文献

Purpose: Esophageal squamous cell carcinoma (ESCC) frequently exhibits skip metastasis to lymph nodes; however, non-invasive imaging techniques capable of directly visualizing metastatic lymph nodes (MLN) are still lacking. Although biopsy is the clinical standard method, it is invasive and poses risks to patient health. This study aims to detect MLN in an intralymphatic tumor metastasis model of ESCC using the CXCR4-targeted tracer [⁶⁴Cu]Cu-NOTA-CP01.

Procedures: The CXCR4 expression in ESCC cell lines was assessed using Western blot and immunofluorescence. An intralymphatic tumor metastasis model was established and monitored using bioluminescence imaging (BLI). Small animal PET studies and biodistribution studies were performed to evaluate the specificity of [⁶⁴Cu]Cu-NOTA-CP01 for MLN. Histopathology evaluation was employed to check for the presence of metastatic tumor cells and to assess CXCR4 expression levels in the metastatic lymph nodes.

Results: The intralymphatic tumor metastasis model was successfully established using the EC109/Luc cell line, which exhibited high CXCR4 expression, as verified by BLI. PET/CT imaging showed that the MLN uptakes in the baseline group were significantly inhibited in the blocking group. The ratios of MLN/muscle and MLN/blood were also significantly higher in the baseline group than in the blocking group. Ex vivo PET/CT imaging of MLN corroborated the in vivo data. Biodistribution studies further supported the PET imaging studies, showing rapid clearance of the tracer from the blood and major organs, with significantly higher MLN/muscle and MLN/blood ratios in the baseline group compared to the blocking group. Histopathological staining verified positive CXCR4 expression in these lymph nodes containing metastatic tumor cells.

Conclusions: Targeting CXCR4 with [⁶⁴Cu]Cu-NOTA-CP01 for PET imaging of lymph nodes metastasis represents a promising approach that warrants further investigation. These findings have the potential to enhance diagnostic and therapeutic strategies for individuals with lymph nodes metastasis of ESCC.

Purpose: Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will be informative to patients and healthcare providers. Our objective was to investigate whether PET imaging with ¹⁸F-Fluorodeoxysorbitol (¹⁸F-FDS) or ¹⁸F-FDG can be used to differentiate responders from non-responders to antibiotic treatment.

Procedures: NTUH-K2044 was used for infection in Albino C57 female mice. Each mouse was inoculated intratracheally with NTUH-K2044 to induce lung infection (n = 8). For treatment studies, two bacterial doses for animal inoculation and two treatment starting times were compared to optimize treatment profiles. ¹⁸F-FDS or ⁸F-FDG /PET imaging was performed to monitor treatment progression.

Results: Our results demonstrated that the treatment profiles for mice infected with 25 CFU hvKp and antibiotic treatment starting at 24 p.i. were not ideal due to no evidence of lung infection and lack of treatment efficacy. The optimal scheme is to use 250 CUF for infection and start antibiotic treatment at 24 h p.i. to monitor antimicrobial efficacy. 75% of the mice were classified as responders to antibiotic treatment. 25% of the mice were classified as non-responders. ¹⁸F-FDG was used to compare with ¹⁸F-FDS, but all mice showed increased lung uptake of ¹⁸F-FDG during 3-day treatments.

Conclusions: ¹⁸F-FDS is a promising PET tracer to image bacterial infection. It can be used to monitor response to treatment, and differentiate responders from non-responders to antibiotic treatment, but ¹⁸F-FDG cannot, probably due to the presence of high degree of inflammation before and after treatment.

Purpose: To evaluate the value of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (^99mTc-GSA) single photon emission computed tomography (SPECT) for assessing liver fibrosis, and to assess its complementary value to other liver function indices such as fibrosis-4 (FIB-4) index and indocyanine green (ICG) clearance test parameters (ICG-R15 and ICG-K).

Procedures: Seventy-eight patients with chronic liver disease and hepatocellular carcinoma who underwent ^99mTc-GSA scintigraphy and other liver function tests including ICG test and FIB-4 index prior to hepatectomy were studied. ^99mTc-GSA imaging was performed with SPECT/CT scanner (Discovery NM/CT 670). Immediately after injection of ^99mTc-GSA, dynamic imaging was performed for 20 min, followed by SPECT data acquisition for 6 min. LHL15 which is a conventional index by ^99mTc-GSA planar images, and liver uptake ration (LUR) was measured from ^99mTc-GSA SPECT images. From the liver resection specimens, the degree of liver fibrosis was graded according to the Ludwig scale (F0-4).

Results: Significant differences in LUR, LHL15, ICG-R15, ICG-K, platelet count and FIB-4 index were found between the F0-3 and F4 liver fibrosis patient groups (P < 0.05). Multivariate logistic regression analysis revealed that LUR and ICG-K were independent factors for identifying severe liver fibrosis (F4). Area under the curve of receiver operating curve analysis for the logistic regression model using LUR and ICG-K was 0.83. In the patient group with higher FIB-4 (≥ 3.16), the diagnostic performance of LUR for detecting severe liver fibrosis was significantly better than LHL15 (AUC: 0.83 vs. 0.75, P = 0.048). In the high FIB-4 index group, the sensitivity and specificity for identifying F4 was 88% and 85%, respectively, with LUR cutoff value of 41.2%.

Conclusions: LUR, measured by ^99mTc-GSA SPECT, is a useful indicator for identifying sever liver fibrosis. Particularly in patients with high FIB-4 index (≥ 3.16), LUR can be a valuable indicator to identify severe liver fibrosis with high diagnostic accuracy.

Purpose: Accurate clinical staging of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is critical for establishing optimal treatment strategies. While the efficacy of fluorine-18-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) in clinical staging is unclear, PET/CT detecting fibroblast-activation protein (FAP) expression has recently received considerable attention for detecting various tumors, including PDAC, with high sensitivity. We explored the efficacy of [¹⁸F]FDG and [¹⁸F]AIF-FAPI-74 PET/CT in the initial evaluation of potentially resectable PDAC.

Procedures: Between 2021 and 2022, twenty participants with newly diagnosed potentially resectable PDAC were enrolled. After the initial evaluation with pancreatic CT, [¹⁸F]FDG PET/CT, and [¹⁸F]AIF-FAPI-74 PET/CT, treatment strategies were determined considering the participant's general status, clinical staging, and resectability. Pathological information from the surgical specimens was only available in 17 participants who underwent curative-intent surgery. Head-to-head comparisons of quantitative radiotracer uptake and diagnostic performance were performed among imaging modalities.

Results: [¹⁸F]AIF-FAPI-74 PET/CT showed a significantly higher maximum standardized uptake value than [¹⁸F]FDG PET/CT did in evaluating primary pancreatic lesions (median [interquartile range]; 12.6 [10.7-13.7] vs. 6.3 [4.8-9.2]; P < 0.001). In contrast, [¹⁸F]AIF-FAPI-74 PET/CT showed a significantly lower mean standardized uptake value than [¹⁸F]FDG PET/CT did in evaluating background organ (median [interquartile range]) 0.8 [0.7-0.9] vs. 2.6 [2.3-2.7]; P < 0.001). In addition, the sensitivity of [¹⁸F]AIF-FAPI-74 PET/CT in detecting metastatic lymph nodes was higher than that of [¹⁸F]FDG PET/CT (50.0% vs. 0.0%; P = 0.026).

Conclusion: This study demonstrated that [¹⁸F]AIF-FAPI-74 PET/CT could improve the clinical staging of potentially resectable PDAC.

Purpose: This study aimed to develop a novel method for real-time imaging to track macrophages and to make it possible to visually track their dynamic features.

Procedures: The archaeon Halobacterium NRC-1 was cultured in an ATCC medium. Buoyant cells were allowed to produce biosynthetic gas vesicles (GVs), and isolated GVs were collected after lysis. Gas vesicle-labelled macrophages (GV@RAWs) were obtained by incubating macrophage (RAW 264.7) cells with GVs. The ability of GV@RAWs to track macrophages in real-time for a long term was assessed using a high-frequency ultrasound imaging system.

Results: We successfully synthesised and isolated GV@RAWs by co-incubating them with RAW 264.7. The results showed that GV@RAW produced significant ultrasound signals without affecting cell survival and could achieve real-time imaging for up to 3 days in vitro.

Conclusion: This research provides a new way to achieve long-term real-time imaging of macrophages, opening up new possibilities for immune response research, clinical diagnosis and therapeutic strategies for inflammatory diseases.

Purpose: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, ¹⁸F-labeled 2'-deoxy-2'-¹⁸F-fluoro-9-β-d-arabinofuranosylguanine ([¹⁸F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.

Procedure: To test whether the myocardial [¹⁸F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [¹⁸F]F-AraG uptake in normal heart by comparing [¹⁸F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [¹⁸F]F-AraG and 2-deoxy-2[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [¹⁸F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.

Results: The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [¹⁸F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [¹⁸F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [¹⁸F]FDG signals showed wider variability at different time points. Noticeable [¹⁸F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.

Conclusions: Our preliminary preclinical data show that [¹⁸F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.

Purpose: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection.

Procedures: Seventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [¹⁸F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard.

Results: Nine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm³, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555-0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571-0.964), respectively.

Conclusions: Volumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [¹⁸F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection.