Objectives The aim of this study was to quantify acute myocardial retention of cardiac-derived stem cells (CDCs) and evaluate different delivery methods with positron emission tomography (PET). ...Background Success of stem cell transplantation for cardiac regeneration is partially limited by low retention/engraftment of the delivered cells. A clinically applicable method for accurate quantification of cell retention would enable optimization of cell delivery. Methods The CDCs were derived from syngeneic, male Wistar Kyoto (WK) rats labeled with 18 F-fluoro-deoxy-glucose (18 FDG) and injected intramyocardially into the ischemic region of female WK rats after permanent left coronary artery ligation. The effects of fibrin glue (FG), bradycardia (adenosine), and cardiac arrest were examined. Imaging with18 FDG PET was performed for quantification of cell retention. Quantitative polymerase chain reaction (PCR) for the male-specific SRY gene was performed to validate the PET results. Results Myocardial retention of cells suspended in phosphate-buffered saline 1 h after delivery was 17.6 ± 11.5% by PCR and 17.8 ± 7.3% by PET. When CDCs were injected immediately after induction of cardiac arrest, retention was increased to 75.6 ± 18.6%. Adenosine slowed the ventricular rate and doubled CDC retention (35.4 ± 5.3%). A similar increase in CDC retention was observed after epicardial application of FG at the injection site (37.5 ± 8.2%). The PCR revealed a significant increase in 3-week cell engraftment in the FG animals (22.1 ± 18.6% and 5.3 ± 3.1%, for FG and phosphate-buffered saline, respectively). Conclusions In vivo PET permits accurate measurement of CDC retention early after intramyocardial delivery. Sealing injection sites with FG or lowering ventricular rate by adenosine might be clinically translatable methods for improving stem cell engraftment in a beating heart.
Expression of programmed cell death ligand 1 (PD-L1) within tumors is an important biomarker for guiding immune checkpoint therapies; however, immunohistochemistry-based methods of detection fail to ...provide a comprehensive picture of PD-L1 levels in an entire patient. To facilitate quantification of PD-L1 in the whole body, we developed a peptide-based, high-affinity PD-L1 imaging agent labeled with 18Ffluoride for positron emission tomography (PET) imaging. The parent peptide, WL12, and the nonradioactive analog of the radiotracer, 19FPy-WL12, inhibit PD-1/PD-L1 interaction at low nanomolar concentrations (half maximal inhibitory concentration IC50, 26-32 nM). The radiotracer, 18FFPy-WL12, was prepared by conjugating 2,3,5,6-tetrafluorophenyl 6-18Ffluoronicotinate (18FFPy-TFP) to WL12 and assessed for specificity in vitro in 6 cancer cell lines with varying PD-L1 expression. The uptake of the radiotracer reflected the PD-L1 expression assessed by flow cytometry. Next, we performed the in vivo evaluation of 18FFPy-WL12 in mice bearing cancer xenografts by PET imaging, ex vivo biodistribution, and blocking studies. In vivo data demonstrated a PD-L1-specific uptake of 18FFPy-WL12 in tumors that is reduced in mice receiving a blocking dose. The majority of 18FFPy-WL12 radioactivity was localized in the tumors, liver, and kidneys indicating the need for optimization of the labeling strategy to improve the in vivo pharmacokinetics of the radiotracer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Stereotactic ablative radiation therapy (SABR) for oligometastatic prostate cancer (OMPC) may improve clinical outcomes, but current challenges in intrafraction tracking of multiple small targets ...limits treatment accuracy. A biology-guided radiation therapy (BgRT) delivery system incorporating positron emission tomography (PET) detectors is being developed to use radiotracer uptake as a biologic fiducial for intrafraction tumor tracking to improve geometric accuracy. This study simulates prostate-specific membrane antigen (PSMA)-directed BgRT using a cohort from our phase II randomized trial of SABR in men with recurrent hormone sensitive OMPC and compares dose distributions to clinical SABR (CSABR).
A research treatment planning system (RTPS) was used to replan 15 patients imaged with PSMA-targeted 18F-DCFPyL PET/computed tomography and previously treated with CSABR using conventional linear accelerators (linacs). The RTPS models a prototype ring-mounted linac incorporating PET and kilo-voltage computed tomography imaging subsystems and can be used to optimize BgRT plans, as well as research SABR (RSABR) plans, which use the prototype linac without radiotracer guidance. CSABR, RSABR, and BgRT plans were compared in terms of maximum planning target volume (PTV) dose (Dmax), mean dose to proximal organs at risk (DOAR), conformity index, as well as voxel-wise correlation of dose with PET specific uptake values to investigate possible dose-painting effects.
RSABR and BgRT plans resulted in mean ± standard deviation increases in Dmax of 4 ± 11% (P = .21) and 18 ± 15% (P < .001) and reductions in DOAR of –20 ± 19% (P <.001) and –10 ± 19% (P = .02) compared with CSABR. Similar target coverage was maintained with conformity indices of 0.81 ± 0.04 (P < .001) and 0.72 ± 0.08 (P = .44) for RSABR and BgRT compared with 0.74 ± 0.08 for CSABR. Dose and log (specific uptake values) had Pearson correlation coefficients of 0.10 (CSABR), 0.16 (RSABR), and 0.31 (BgRT).
BgRT plans provided similar PTV coverage and conformity compared with CSABR while incorporating underlying PET activity. These results demonstrate feasibility of BgRT optimization enabling online PSMA-targeted, PET-based tracked dose delivery for OMPC.
Purpose:
Imaging is limited in the evaluation of bacterial infection. Direct imaging of in situ bacteria holds promise for noninvasive diagnosis. We investigated the ability of a bacterial thymidine ...kinase inhibitor (124IFIAU) to image pulmonary and musculoskeletal infections.
Methods:
Thirty-three patients were prospectively accrued: 16 with suspected musculoskeletal infection, 14 with suspected pulmonary infection, and 3 with known rheumatoid arthritis without infection. Thirty-one patients were imaged with 124IFIAU PET/CT and 28 with 18FFDG PET/CT. Patient histories were reviewed by an experienced clinician with subspecialty training in infectious diseases and were determined to be positive, equivocal, or negative for infection.
Results:
Sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of 124IFIAU PET/CT for diagnosing infection were estimated as 7.7% to 25.0%, 0.0%, 50%, 0.0%, and 20.0% to 71.4% for musculoskeletal infections and incalculable-100.0%, 51.7% to 72.7%, 0.0% to 50.0%, 100.0%, and 57.1% to 78.6% for pulmonary infections, respectively. The parameters for 18FFDG PET/CT were 75.0% to 92.3%, 0.0%, 23.1% to 92.3%, 0.0%, and 21.4% to 85.7%, respectively, for musculoskeletal infections and incalculable to 100.0%, 0.0%, 0.0% to 18.2%, incalculable, and 0.0% to 18.2% for pulmonary infections, respectively.
Conclusions:
The high number of patients with equivocal clinical findings prevented definitive conclusions from being made regarding the diagnostic efficacy of 124IFIAU. Future studies using microbiology to rigorously define infection in patients and PET radiotracers optimized for image quality are needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prostate-specific membrane antigen (PSMA) has been explored as a target for molecular imaging of prostate cancer and other malignancies that express PSMA in their tumor-associated neovasculature. ...Although several PSMA-targeted radiotracers labeled with a variety of radionuclides have been reported, positron-emitting radiotracers labeled with
F are of particular interest. One such compound, the small molecule PSMA inhibitor
FDCFPyL, has demonstrated initial success. This article reviews the literature on this radiotracer, including radiosynthetic approaches to the molecule, data that are available from preclinical experiments, and evidence to date of the clinical utility of this agent in prostate cancer and clear cell renal cell carcinoma.
Anatomically based technologies (computed tomography scans, magnetic resonance imaging, and so on) are in routine use in radiotherapy for planning and assessment purposes. Even with improvements in ...imaging, however, radiotherapy is still limited in efficacy and toxicity in certain applications. Further advances may be provided by technologies that image the molecular activities of tumors and normal tissues. Possible uses for molecular imaging include better localization of tumor regions and early assay for the radiation response of tumors and normal tissues. Critical to the success of this approach is the identification and validation of molecular probes that are suitable in the radiotherapy context. Recent developments in molecular-imaging probes and integration of functional imaging with radiotherapy are promising. This review focuses on recent advances in molecular imaging strategies and probes that may aid in improving the efficacy of radiotherapy.
SummaryChimeric antigen receptor (CAR) T-cell therapy is one of the most remarkable advances in cancer therapy in the last several decades. More than 300 adoptive T-cell therapy trials are ongoing, ...which is a testament to the early success and hope engendered by this line of investigation. Despite the enthusiasm, application of CAR T-cell therapy to solid tumours has had little success, although positive outcomes are increasingly being reported for these diseases. In this Series paper, we discuss the short-term strategies to improve CAR T-cell therapy responses, particularly for solid tumours, by combining CAR T-cell therapy with radiotherapy through the use of careful monitoring and non-invasive imaging. Through the use of imaging, we can gain greater mechanistic insights into the cascade of events that must unfold to enable tumour eradication by CAR T-cell therapy.
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