scholarly journals PET/CT Imaging of Head-and-Neck and Pancreatic Cancer in Humans by Targeting the "Cancer Integrin" αvβ6 with Ga-68-Trivehexin

2021 ◽  
Author(s):  
Neil Gerard Quigley ◽  
Katja Steiger ◽  
Sebastian Hoberück ◽  
Norbert Czech ◽  
Maximilian Alexander Zierke ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ct Imaging ◽  
Binding Assays ◽  
Cell Binding ◽  
Integrin Αvβ6 ◽  
Pet Ct ◽  
Preclinical Pet ◽  
Specific Uptake ◽  
Αvβ6 Integrin ◽  
Automated Labeling

Abstract PurposeTo develop a new probe for the αvβ6-integrin and assess its potential for PET imaging of carcinomas.MethodsGa-68-Trivehexin was synthesized by trimerization of an optimized αvβ6-integrin selective cyclicnonapeptide on the TRAP chelator core and automated labeling with Ga-68. The tracer wascharacterized by ELISA for activities towards integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1, as well asby cell binding assays on H2009 (αvβ6-positive) and MDA-MB-231 (αvβ6-negative) cells. SCID micebearing subcutaneous xenografts of the same cell lines were used for dynamic (90 min) and static(75 min p.i.) μPET imaging, as well as for biodistribution (90 min p.i.). Structure-activity-relationshipswere established by comparison with the predecessor compound Ga-68-TRAP(AvB6)3. Ga-68-Trivehexin was tested for in-human PET/CT imaging of HNSCC, parotideal adenocarcinoma, andPDAC.ResultsGa-68-Trivehexin showed a high αvβ6-integrin affinity (IC50 = 0.033 nM), selectivity over othersubtypes (IC50-based factors: αvβ8, 188; αvβ3, 82; α5β1, 667), blockable uptake in H2009 cells, andnegligible uptake in MDA-MB-231 cells. Biodistribution and preclinical PET imaging confirmed a hightarget-specific uptake in tumor and a low non-specific uptake in other organs and tissues except theexcretory organs (kidneys and urinary bladder). Preclinical PET corresponded well to in-human results,showing high and persistent uptake in metastatic PDAC and HNSCC (SUVmax = 10–13) as well as inkidneys/urine. Ga-68-Trivehexin enabled PET/CT imaging of small PDAC metastases and showed highuptake in HNSCC but not in tumor-associated inflammation.ConclusionsGa-68-Trivehexin is a valuable probe for imaging of αvβ6-integrin expression in human cancers.

scholarly journals PET/CT imaging of head-and-neck and pancreatic cancer in humans by targeting the “Cancer Integrin” αvβ6 with Ga-68-Trivehexin

2021 ◽  
Author(s):  
Neil Gerard Quigley ◽  
Katja Steiger ◽  
Sebastian Hoberück ◽  
Norbert Czech ◽  
Maximilian Alexander Zierke ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ct Imaging ◽  
Binding Assays ◽  
Cell Binding ◽  
Integrin Αvβ6 ◽  
Pet Ct ◽  
Preclinical Pet ◽  
Specific Uptake ◽  
Αvβ6 Integrin ◽  
Automated Labeling

Abstract Purpose To develop a new probe for the αvβ6-integrin and assess its potential for PET imaging of carcinomas. Methods Ga-68-Trivehexin was synthesized by trimerization of the optimized αvβ6-integrin selective cyclic nonapeptide Tyr2 (sequence: c[YRGDLAYp(NMe)K]) on the TRAP chelator core, followed by automated labeling with Ga-68. The tracer was characterized by ELISA for activities towards integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1, as well as by cell binding assays on H2009 (αvβ6-positive) and MDA-MB-231 (αvβ6-negative) cells. SCID-mice bearing subcutaneous xenografts of the same cell lines were used for dynamic (90 min) and static (75 min p.i.) µPET imaging, as well as for biodistribution (90 min p.i.). Structure–activity-relationships were established by comparison with the predecessor compound Ga-68-TRAP(AvB6)3. Ga-68-Trivehexin was tested for in-human PET/CT imaging of HNSCC, parotideal adenocarcinoma, and metastatic PDAC. Results Ga-68-Trivehexin showed a high αvβ6-integrin affinity (IC50 = 0.047 nM), selectivity over other subtypes (IC50-based factors: αvβ8, 131; αvβ3, 57; α5β1, 468), blockable uptake in H2009 cells, and negligible uptake in MDA-MB-231 cells. Biodistribution and preclinical PET imaging confirmed a high target-specific uptake in tumor and a low non-specific uptake in other organs and tissues except the excretory organs (kidneys and urinary bladder). Preclinical PET corresponded well to in-human results, showing high and persistent uptake in metastatic PDAC and HNSCC (SUVmax = 10–13) as well as in kidneys/urine. Ga-68-Trivehexin enabled PET/CT imaging of small PDAC metastases and showed high uptake in HNSCC but not in tumor-associated inflammation. Conclusions Ga-68-Trivehexin is a valuable probe for imaging of αvβ6-integrin expression in human cancers.

scholarly journals Preclinical and Exploratory Clinical Studies of Novel 68Ga-labeled ᴅ-Peptide Antagonist for PET Imaging of TIGIT Expression in Cancers

2021 ◽  
Author(s):  
Xiaobo Wang ◽  
Ming Zhou ◽  
Bei Chen ◽  
Huanhuan Liu ◽  
Jianyang Fang ◽  
...  
Keyword(s):  
Pilot Study ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Ct Imaging ◽  
Whole Body ◽  
Binding Assays ◽  
Pet Ct ◽  
Peptide Antagonist

Abstract Purpose While TIGIT has been propelled under the spotlight as a next-generation target in cancer immunotherapy, anti-TIGIT therapy seems to be promising for a fraction of patients in clinical trials. Therefore, patient stratification is critical for this therapy, which could benefit from a whole-body, non-invasive and quantitative evaluation of TIGIT expression in cancers. In this study, a 68Ga-labeled ᴅ-peptide antagonist, 68Ga-GP12, was developed and validated for PET imaging of TIGIT expression in vitro, in vivo, and first-in-human pilot study. Methods The ᴅ-enantiomer peptide antagonists were modified and radiolabeled with 68Ga. In vitro binding assays were performed in human peripheral blood mononuclear cells (PBMCs) to assess their affinity and specificity. The imaging capacity, biodistribution, pharmacokinetics, and radiation dosimetry were investigated in vivo. Flow cytometry, autoradiography, and immunohistochemical staining were used to confirm the expression of TIGIT ex vivo. The safety and potential of 68Ga-GP12 for PET/CT imaging of TIGIT expression were further evaluated in a first-in-human pilot study with advanced NSCLC. Results 68Ga-labeled ᴅ-peptides were conveniently produced with high radiochemical yields,radiochemical purity and molar activities. In vitro binding assays demonstrated 68Ga-GP12 has favorable affinity and specificity for TIGIT with a KD of 37.28 nM. In vivo and ex vivo studies demonstrated the favorable pharmacokinetics of 68Ga-GP12 for PET imaging of TIGIT expression with high tumor uptake of 4.22 ± 0.68 %ID/g and the tumor-to-muscle ratio of 12.94 ± 2.64 at 60 min post-injection. The primary and metastatic lesions found in the first-in-human studies of 68Ga-GP12 PET/CT imaging were comparable to that in 18F-FDG PET/CT imaging. Moreover, the inhomogenous intra-and-inter-tumoral uptake of 68Ga-GP12 was presented, reflecting the heterogeneity of TIGIT expression levels. Conclusion 68Ga-GP12 is a promising radiotracer for PET imaging of TIGIT expression in cancers, indicating its potential as a potential companion diagnostic for anti-TIGIT therapies.

scholarly journals The incremental value of dual modality PET/CT imaging over PET imaging alone in advanced colorectal cancer

2009 ◽  
Vol 71 (2) ◽  
pp. 63-68 ◽  
Author(s):  
A. H. Engledow ◽  
G. E. L. Bond-Smith ◽  
D. Francis ◽  
F. Pakzad ◽  
J. Bomanji ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pet Imaging ◽  
Advanced Colorectal Cancer ◽  
Ct Imaging ◽  
Dual Modality ◽  
Incremental Value ◽  
Pet Ct

scholarly journals Molecular PET Imaging of Cyclophosphamide Induced Apoptosis with18F-ML-8

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shaobo Yao ◽  
Kongzhen Hu ◽  
Ganghua Tang ◽  
Siyuan Gao ◽  
Caihua Tang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Experimental Result ◽  
Tunel Staining ◽  
Binding Assays ◽  
Cell Binding ◽  
Imaging Probe ◽  
Tumor Bearing ◽  
Antitumor Chemotherapy ◽  
Induced Apoptosis

In this paper, a novel small-molecular apoptotic PET imaging probe,18F-ML-8 with a malonate motif structure, is presented and discussed. After study, the small tracer that belongs to a member of ApoSense family is proved to be capable of imaging merely apoptotic regions in the CTX treated tumor-bearing mice. The experimental result is further confirmed by in vitro cell binding assays and TUNEL staining assay. As a result,18F-ML-8 could be used for noninvasive visualization of apoptosis induced by antitumor chemotherapy.

scholarly journals Assessing and reducing PET radiotracer infiltration rates: a single center experience in injection quality monitoring methods and quality improvement

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Dustin R. Osborne ◽  
Shelley N. Acuff ◽  
Michael Fang ◽  
Melissa D. Weaver ◽  
Yitong Fu
Keyword(s):  
Quality Improvement ◽  
Pet Imaging ◽  
Infiltration Rate ◽  
Radiation Detectors ◽  
Ct Imaging ◽  
The Body ◽  
Infiltration Rates ◽  
Improvement Plan ◽  
Imaging Results ◽  
Pet Ct

Abstract Background Successful injection of radiolabeled compounds is critical for positron emission tomography (PET) imaging. A poor quality injection limits the tracer availability in the body and can impact diagnostic results. In this study, we attempt to quantify our infiltration rates, develop an actionable quality improvement plan to reduce potentially compromised injections, and compare injection scoring to PET/CT imaging results. Methods A commercially available system that uses external radiation detectors was used to monitor and score injection quality. This system compares the time activity curves of the bolus relative to a control reading in order to provide a score related to the quality of the injection. These injection scores were used to assess infiltration rates at our facility in order to develop and implement a quality improvement plan for our PET imaging center. Injection scores and PET imaging results were reviewed to determine correlations between image-based assessments of infiltration, such as liver SUVs, and injection scoring, as well as to gather infiltration reporting statistics by physicians. Results A total of 1033 injections were monitored at our center. The phase 1 infiltration rate was 2.1%. In decision tree analysis, patients < 132.5lbs were associated with infiltrations. Additional analyses suggested patients > 127.5 lbs. with non-antecubital injections were associated with lower quality injections. Our phase 2 infiltration rate was 1.9%. Comparison of injection score to SUV showed no significant correlation and indicated that only 63% of suspected infiltrations were visible on PET/CT imaging. Conclusions Developing a quality improvement plan and monitoring PET injections can lead to reduced infiltration rates. No significant correlation between reference SUVs and injection score provides evidence that determination of infiltration based on PET images alone may be limited. Results also indicate that the number of infiltrated PET injections is under-reported.

Comparison of Contrast-Enhanced CT, PET/CT, PET, and Low-Dose Non-Contrast Enhanced CT Imaging of Diffuse Large B-Cell, Follicular, Small Lymphocytic/CLL, and Marginal Zone Lymphomas.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1402-1402 ◽  
Author(s):  
Elise A. Chong ◽  
Drew A. Torigian ◽  
Abass Alavi ◽  
Jakub Svoboda ◽  
Anthony R Mato ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Low Dose ◽  
Imaging Modality ◽  
Ct Imaging ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced ◽  
Pet Ct ◽  
Enhanced Ct ◽  
Ct Studies

Abstract Abstract 1402 Poster Board I-424 Introduction: Anatomic imaging using contrast-enhanced computed tomography (CT) is essential for management of lymphomas. Functional imaging using 18FDG-PET (PET) improves detection of certain lymphomas, specifically, diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Currently, PET imaging is performed with co-registration of low-dose non-contrast enhanced CT images used for anatomic correlation and attenuation correction of PET images (PET/CT). It has been suggested that the low-dose non-enhanced CT cannot substitute for diagnostic contrast-enhanced CT imaging since the arterial and venous phases of contrast enhancement improve detection of lesions. Given the differential sensitivity for detection of specific lymphomas by PET imaging, we hypothesized that FDG could substitute for intravenous contrast in imaging of certain lymphomas, and that PET/CT or PET imaging could potentially obviate the need for contrast-enhanced CT. To test this hypothesis, we performed an independent and blinded radiology review of these imaging studies in patients (pts) with DLBCL, FL, small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL) or marginal zone lymphoma (MZL) who had contrast-enhanced CT, PET, PET/CT, and low-dose non-enhanced CT available for retrospective review. Patients and Methods: Pts with a diagnosis of DLBCL, FL, CLL/SLL, or MZL with PET/CT and contrast-enhanced CT studies performed at the Hospital of the University of Pennsylvania within 6 weeks of each other without intervening therapy were studied. Pts with clinically suspected progression of lymphoma between studies were excluded. Radiologists, blinded to clinical information or other imaging results, separately interpreted image sets of low-dose non-enhanced CT, PET, fusion PET/CT, and contrast-enhanced CT studies. The presence or absence of disease at 44 nodal and 48 (female) or 49 (male) extranodal sites was recorded for each site for each imaging modality. Concordant findings across imaging modalities were defined as positive for involvement by lymphoma; discordant findings were reconciled using all available clinical and radiologic information with follow-up for progression or regression of abnormality, or by biopsy. Results: Between May 2006 and January 2008, 55 pts with either DLBCL (n=31), FL (n=13), CLL/SLL (n=5), or MZL (n=6) had complete images sets available for review. All patients had at least 18 months of clinical follow-up after imaging. A total of 282 sites met criteria for involvement by lymphoma. The rates of detection for specific lymphomas by each imaging modality are shown below: Conclusions: Our results suggest that combined PET/CT imaging is more sensitive than contrast-enhanced CT imaging for detection of DLBCL and at least as sensitive as contrast-enhanced CT imaging for detection of FL. In comparison, contrast-enhanced CT imaging appears superior to PET/CT imaging for CLL/SLL; while further studies are needed to confirm superiority of contrast-enhanced CT imaging in MZL. The routine use of both contrast enhanced CT and PET/CT modalities for staging of lymphoma may be unnecessary, potentially increasing both the cost of medical care and radiation exposure. Additional studies are needed to determine which imaging modality is optimal for each type of lymphoma. Disclosures: No relevant conflicts of interest to declare.

[89Zr]Zr(oxinate)4 Allows Direct Radiolabelling and PET Imaging of Small Extracellular Vesicles

2021 ◽  
Author(s):  
Azalea Khan ◽  
Francis Man ◽  
Farid Faruqu ◽  
Jana Kim ◽  
Fahad Al-Salemee ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Pet Imaging ◽  
Ct Imaging ◽  
Pet Ct

89Zr]Zr(oxinate)4 allows direct radiolabelling of exosomes/small extracellular vesicles (sEVs) and in vivo PET-CT imaging

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