Pattern of F-18 FDG Uptake in Colon Cancer after Bacterial Cancer Therapy Using Engineered Salmonella Typhimurium: A Preliminary In Vivo StudyRead the full article
Molecular Imaging is a peer-reviewed journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. Molecular Imaging covers all imaging modalities.
Chief Editor Henry VanBrocklin is a Professor at the University of California, San Francisco, USA, and Director of its Radiopharmaceutical Research Program. His research interests include short-lived radioisotope production and the creation of fluorine-18 and carbon-11 labeling chemistry strategies
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Prostate-Specific Membrane Antigen as Target for Neuroimaging of Central Nervous System Tumors
Introduction. Positron emission tomography (PET) imaging with prostate-specific membrane antigen- (PSMA-) binding tracers has been found incidentally to demonstrate uptake in CNS tumors. Following the encouraging findings of several such case reports, there is a growing interest in the potential application of PSMA-targeted PET imaging for diagnostics, theranostics, and monitoring of CNS tumors. This is a systematic literature review on PSMA-binding tracers in CNS tumors. Methods. A PubMed search was conducted, including preclinical and clinical reports. One hundred and twelve records were identified, and after screening, 56 were included in the final report. Results. Tissue studies demonstrated PSMA expression in tumor vascular endothelial cells, without expression in normal brain tissue, though the extent and intensity of staining varied by anti-PSMA antibody and methodology. Most included studies reported on gliomas, which showed strong PSMA ligand uptake and more favorable tumor to background ratios than other PET tracers. There are also case reports demonstrating PSMA ligand uptake in prostate cancer brain metastases, nonprostate cancer brain metastases, and meningiomas. We also review the properties of the various PSMA-binding radiotracers available. Therapeutic and theranostic applications of PSMA-binding tracers have been studied, including labeled alpha- and beta-ray emitting isotopes, as well as PSMA targeting in directing MRI-guided focused ultrasound. Conclusions. There is a potential application for PSMA-targeted PET in neuro-oncology as a combination of diagnostic and therapeutic use, as a theranostic modality for managing CNS tumors. Further research is needed regarding the mechanism(s) of PSMA expression in CNS tumors and its differential performance by tumor type.
Near-Infrared Fluorescence Imaging of EGFR-Overexpressing Tumors in the Mouse Xenograft Model Using scFv-IRDye800CW and Cetuximab-IRDye800CW
EGFR (epidermal growth factor receptor) is overexpressed in a variety of human cancers (including squamous cell carcinoma of head and neck, colon cancer, and some breast cancers) and therefore is regarded as an ideal target for cancer therapy or imaging purposes. In the current study, we produced a scFv-based near-infrared probe (called cet.Hum.scFv-IRDye-800CW) and evaluated its ability in recognizing and imaging of EGFR-overexpressing tumors in a mouse model. Like the molecular probe consisting of its parental antibody (cetuximab, an FDA-approved monoclonal antibody) and IRD800CW, cet.Hum.scFv-IRDye-800CW was able to recognize EGFR-overexpressing tumors in mice. cet.Hum.scFv-IRDye-800CW was found to be superior to the cetuximab-based probe in imaging of mouse tumors. The tumor-to-background ratio and blood clearance rate were higher when cet.Hum.scFv-IRDye-800CW was used as an imaging probe.
The Probe for Renal Organic Cation Secretion (4-Dimethylaminostyryl)-N-Methylpyridinium (ASP+)) Shows Amplified Fluorescence by Binding to Albumin and Is Accumulated In Vivo
Accumulation of uremic toxins may lead to the life-threatening condition “uremic syndrome” in patients with advanced chronic kidney disease (CKD) requiring renal replacement therapy. Clinical evaluation of proximal tubular secretion of organic cations (OC), of which some are uremic toxins, is desired, but difficult. The biomedical knowledge on OC secretion and cellular transport partly relies on studies using the fluorescent tracer 4-dimethylaminostyryl)-N-methylpyridinium (ASP+), which has been used in many studies of renal excretion mechanisms of organic ions and which could be a candidate as a PET tracer. This study is aimed at expanding the knowledge of the tracer characteristics of ASP+ by recording the distribution and intensity of ASP+ signals in vivo both by fluorescence and by positron emission tomography (PET) imaging and at investigating if the fluorescence signal of ASP+ is influenced by the presence of albumin. Two-photon in vivo microscopy of male Münich Wistar Frömter rats showed that a bolus injection of ASP+ conferred a fluorescence signal to the blood plasma lasting for about 30 minutes. In the renal proximal tubule, the bolus resulted in a complex pattern of fluorescence including a rapid and strong transient signal at the brush border, a very low signal in the luminal fluid, and a slow transient intracellular signal. PET imaging using 11C-labelled ASP+ showed accumulation in the liver, heart, and kidney. Fluorescence emission spectra recorded in vitro of ASP+ alone and in the presence of albumin using both 1-photon excitation and two-photon excitation showed that albumin strongly enhance the emission from ASP+ and induce a shift of the emission maximum from 600 to 570 nm. Conclusion. The renal pattern of fluorescence observed from ASP+ in vivo is likely affected by the local concentration of albumin, and quantification of ASP+ fluorescent signals in vivo cannot be directly translated to ASP+ concentrations.
The Potential Prognostic Value of Dual-Imaging PET Parameters Based on 18F-FDG and 18F-OC for Neuroendocrine Neoplasms
Background. To identify parameters based on dual-imaging 18F-AlF-NOTA-octreotide (18F-OC) and 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) for predicting the prognosis of neuroendocrine neoplasms (NENs). Materials and Methods. Sixty-six patients (age: (SD): years) who underwent both 18F-OC and 18F-FDG PET/CT imaging were enrolled in our retrospective study. The following PET parameters were measured: the maximum standardized uptake value (SUVmax) and the volumetric parameters—18F-OC SSR-derived tumor volume (TV) and somatostatin receptor expression (SRE, TV multiplied by the mean standardized uptake value (SUVmean)) and the 18F-FDG-derived multiple tumor volume (MTV) and tumor lesion glycolysis (TLG). The NETPET grade based on dual-imaging PET images was assessed. Progression-free survival (PFS) was set as an endpoint. Univariate and multivariate survival analyses were performed for PET parameters and clinical tumor data. Results. In the univariate survival analyses of clinical information, PFS was significantly associated with age (>45.5 vs ≤45.5, years, ) and the presence of bone metastases (). Higher values for the 18F-FDG and 18F-OC volumetric parameters and the NETPET grade were adverse factors for PFS according to the dual-imaging PET parameters. In the multivariate survival analysis, the NETPET grade and SRE were predictors of PFS in NEN patients. Conclusion. The NETPET grade is a potential noninvasive prognostic biomarker for NENs.
Evaluation of [18F]tetrafluoroborate as a Potential PET Imaging Agent in a Sodium Iodide Symporter-Transfected Cell Line A549 and Endogenous NIS-Expressing Cell Lines MKN45 and K1
[18F]tetrafluoroborate (TFB) has been introduced as the 18F-labeled PET imaging probe for the human sodium iodide symporter (NIS). Noninvasive NIS imaging using [18F]TFB has received much interest in recent years for evaluating various NIS-expressing tumors. Cancers are a global concern with enormous implications; therefore, improving diagnostic methods for accurate detection of cancer is extremely important. Our aim was to investigate the PET imaging capabilities of [18F]TFB in NIS-transfected lung cell line A549 and endogenous NIS-expressing tumor cells, such as thyroid cancer K1 and gastric cancer MKN45, and broaden its application in the medical field. Western blot and flow cytometry were used to assess the NIS expression level. Radioactivity counts of [18F]TFB, in vitro, in the three tumor cells were substantially higher than those in the KI inhibition group in the uptake experiment. In vivo PET imaging clearly delineated the three tumors based on the specific accumulation of [18F]TFB in a mouse model. Ex vivo biodistribution investigation showed high [18F]TFB absorption in the tumor location, which was consistent with the PET imaging results. These results support the use of NIS-transfected lung cell line A549 and NIS-expressing tumor cells MKN45 and K1, to investigate probing capabilities of [18F]TFB. We also demonstrate, for the first time, the feasibility of [18F]TFB in diagnosing stomach cancer. In conclusion, this study illustrates the promising future of [18F]TFB for tumor diagnosis and NIS reporter imaging.
High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with 18F-DCFPyL
Objectives. In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with 18F-DCFPyL. Methods. In this prospective, IRB-approved trial (NCT03793543), 21 patients with history of histologically proven PC underwent two 18F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUVmax) and mean (SUVmean) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as )). Repeatability was determined using Pearson’s correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. Results. In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUVmax (1.5–80.5) and SUVmean (1.4–24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation (), with high repeatability for SUVmean and SUVmax (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs (), indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low (%). Across all metrics for LN and bone lesions, interscan correlation was again strong (). Moreover, LN-based SUVmean also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, ). This was also noted for SUVmax (wCOV, LN 8.8% vs. bone 12.0%, ). On a compartment-based level, wCOVs for volumetric features were ≥22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, P =0.63; TL-PSMA, P =0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUVmax of the most intense lesion per patient (, 0.99; wCOV, 11.2%). Conclusion. In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability.