scholarly journals A Humanized Anti-GPC3 Antibody for Immuno-Positron Emission Tomography Imaging of Orthotopic Mouse Model of Patient-Derived Hepatocellular Carcinoma Xenografts

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3977
Author(s):  
Arutselvan Natarajan ◽  
Hui Zhang ◽  
Wei Ye ◽  
Lakshmi Huttad ◽  
Mingdian Tan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Positron Emission Tomography Imaging ◽  
Region Of Interest ◽  
Orthotopic Mouse Model ◽  
Nsg Mice ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Pet Ct ◽  
Specific Uptake ◽  
Cdr Grafting

Glypican-3 (GPC3) is an attractive diagnostic marker for hepatocellular carcinoma (HCC). We previously reported the potential of an 89Zr-labeled murine anti-GPC3 antibody (clone 1G12) for immunoPET imaging of HCC in orthotopic patient-derived xenograft (PDX) mouse models. We now humanized the murine antibody by complementarity determining region (CDR) grafting, to allow its clinical translation for human use. The engineered humanized anti-GPC3 antibody, clone H3K3, retained comparable binding affinity and specificity to human GPC3. H3K3 was conjugated with desferrioxamine (Df) and radiolabeled with 89Zr to produce the PET/CT tracer 89Zr-Df-H3K3. When injected into GPC3-expressing orthotopic HCC PDX in NOD SCID Gamma (NSG) mice, 89Zr-Df-H3K3 showed specific high uptake into the orthotopic PDX and minimal, non-specific uptake into the non-tumor bearing liver. Specificity was demonstrated by significantly higher uptake of 89Zr-Df-H3K3 into the non-blocked PDX mice, compared with the blocked PDX mice (which received prior injection of 100 mg of unlabeled H3K3). Region of interest (ROI) analysis showed that the PDX/non-tumor liver ratio was highest (mean ± SD: 3.4 ± 0.31) at 168 h post injection; this ratio was consistent with biodistribution studies at the same time point. Thus, our humanized anti-GPC3 antibody, H3K3, shows encouraging potential for use as an immunoPET tracer for diagnostic imaging of HCC patients.

scholarly journals FDG positron emission tomography imaging and ctDNA detection as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Andrea Gombos ◽  
David Venet ◽  
Lieveke Ameye ◽  
Peter Vuylsteke ◽  
Patrick Neven ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fdg Pet ◽  
Positron Emission Tomography Imaging ◽  
Metastatic Breast ◽  
Endocrine Treatment ◽  
Luminal Breast Cancer ◽  
Positron Emission ◽  
Pet Ct ◽  
The Difference ◽  
Fdg Pet Ct

AbstractBiomarkers to identify patients without benefit from adding everolimus to endocrine treatment in metastatic breast cancer (MBC) are needed. We report the results of the Pearl trial conducted in five Belgian centers assessing 18F-FDG-PET/CT non-response (n = 45) and ctDNA detection (n = 46) after 14 days of exemestane-everolimus (EXE-EVE) to identify MBC patients who will not benefit. The metabolic non-response rate was 66.6%. Median PFS in non-responding patients (using as cut-off 25% for SUVmax decrease) was 3.1 months compared to 6.0 months in those showing response (HR: 0.77, 95% CI: 0.40–1.50, p = 0.44). The difference was significant when using a “post-hoc” cut-off of 15% (PFS 2.2 months vs 6.4 months). ctDNA detection at D14 was associated with PFS: 2.1 months vs 5.0 months (HR-2.5, 95% CI: 1.3–5.0, p = 0.012). Detection of ctDNA and/or the absence of 18F-FDG-PET/CT response after 14 days of EXE-EVE identifies patients with a low probability of benefiting from treatment. Independent validation is needed.

scholarly journals 68Ga-FAPI-04 Versus 18F-FDG PET/CT in the Detection of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Wang ◽  
Wenwei Zhu ◽  
Shuhua Ren ◽  
Yanyan Kong ◽  
Qi Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Fdg Pet ◽  
Tumour Size ◽  
Stromal Fibroblasts ◽  
Standardized Uptake Values ◽  
Positron Emission ◽  
Pet Ct ◽  
Epithelial Tumours ◽  
Fdg Pet Ct ◽  
Higher Sensitivity

BackgroundFibroblast activation protein (FAP) is commonly expressed in activated stromal fibroblasts in various epithelial tumours. Recently, 68Ga-FAPI-04 has been used for tumour imaging in positron emission tomography/computed tomography (PET/CT). This study aimed to compare the diagnostic performances of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in hepatocellular carcinoma (HCC), and to assess factors associated with 68Ga-FAPI-04 uptake in HCC.Materials and MethodsTwenty-nine patients with suspiciously HCC who received both 18F-FDG and 68Ga-FAPI-04 PET/CT were included in this retrospective study. The results were interpreted by two experienced nuclear medicine physicians independently. The maximum and mean standardized uptake values (SUVmax and SUVmean) were measured in the lesions and liver background, respectively. The tumour-to-background ratio (TBR) was then calculated as lesion’s SUVmax divided by background SUVmean.ResultsA total of 35 intrahepatic lesions in 25 patients with HCC were finally involved in the statistical analysis. 68Ga-FAPI-04 PET/CT showed a higher sensitivity than 18F-FDG PET/CT in detecting intrahepatic HCC lesions (85.7% vs. 57.1%, P = 0.002), including in small (≤ 2 cm in diameter; 68.8% vs. 18.8%, P = 0.008) and well- or moderately-differentiated (83.3% vs. 33.3%, P = 0.031) tumors. SUVmax was comparable between 68Ga-FAPI-04 and 18F-FDG (6.96 ± 5.01 vs. 5.89 ± 3.38, P > 0.05), but the TBR was significantly higher in the 68Ga-FAPI-04 group compared with the 18F-FDG group (11.90 ± 8.35 vs. 3.14 ± 1.59, P < 0.001). SUVmax and the TBR in 68Ga-FAPI-04 positive lesions were associated with tumour size (both P < 0.05), but not the remaining clinical and pathological features (all P > 0.05).Conclusions68Ga-FAPI-04 PET/CT is more sensitive than 18F-FDG PET/CT in detecting HCC lesions, and 68Ga-FAPI-04 uptake is correlated mainly with tumour size.

Dose Escalation Biodistribution, Positron Emission Tomography/Computed Tomography Imaging and Dosimetry of a Highly Specific Radionuclide-labeled Non-blocking Nanobody

2021 ◽  
Author(s):  
Yang yanling ◽  
Feng Zhao ◽  
Daquan Chen ◽  
Chao Wang ◽  
Yan Sun ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Nude Mice ◽  
Ex Vivo ◽  
Dose Range ◽  
Emission Tomography ◽  
Humanized Mice ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Pet Ct ◽  
Ex Vivo Biodistribution

Abstract Backgroud: Immunotherapy is a valuable option for the treatment of cancers, and the curative effect anti-PD-1/PD-L1 therapy correlates closely with PD-L1 expression levels. Positron emission tomography (PET) imaging of PD-L1 expression is feasible using 68Ga-NOTA-Nb109 nanobodies. 68Ga-NOTA-Nb109 was generated by radionuclide (68Ga) labeling of Nb109 using a NOTA chelator. To facilitate clinical trials, We explored the optimal dose range of 68Ga-NOTA-Nb109 in BALB/c A375-hPD-L1 tumor-burdened nude mice and C57-hPD-L1 transgenic MC38-hPD-L1 tumor-burdened mice by intravenous of a single intravenous dose of 68Ga-NOTA-Nb109 and confirmed the dose in cynomolgus monkeys. The biodistribution data of cynomolgus monkey PET images were extrapolated to estimate the radiation dose for the adult male using OLINDA2.1 software.Results: 68Ga-NOTA-Nb109 was stable in physiologic media and human serum. Ex vivo biodistribution studies showed rapid and specific uptake in A375-hPDL1 or MC38-hPDL1 tumors. The estimated ED50 was approximately 5.4 µg in humanized mice. The injected mass (0.3–100 µg in nude mice and approximately 1–100 µg in humanized mice) greatly influenced the general biodistribution, with a better tumor-to-background ratio acquired at lower doses of Nb109 (0.3–10 µg in nude mice and approximately 1 µg in humanized mice), indicating maximum uptake in tumors at administered mass doses below the estimated ED50. Therefore, a single 15 μg/kg dose was adopted for the PET/CT imaging in cynomolgus monkey. The highest specific and persistent uptake of the tracer was detected in the spleen, with the exception of the levels in the kidney and urine bladder, which was related to metabolism and excretion. The spleen-to-muscle ratio of the tracer exceeded 10 from immediately to 4 h after administration, indicating that the dose was appropriate. The estimated effective dose was calculated to yield a radiation dose of 4.1 mSv to a patient after injection of 185 MBq of 68Ga-NOTA-Nb109.Conclusion: 68Ga-NOTA-Nb109 showed specific accumulation in hPD-L1 xenografts in ex vivo biodistribution studies and monkey PET/CT imaging. The dose escalation distribution data provided a recommended dose range for further use, and the safety of the tracer was confirmed in dosimetry studies.

scholarly journals Imaging of Hypoxic–Ischemic Penumbra with 18F-fluoromisonidazole PET/CT and Measurement of Related Cerebral Metabolism in Aneurysmal Subarachnoid Hemorrhage

2009 ◽  
Vol 30 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Asita S Sarrafzadeh ◽  
Alexandra Nagel ◽  
Marcus Czabanka ◽  
Timm Denecke ◽  
Peter Vajkoczy ◽  
...  
Keyword(s):  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Metabolism ◽  
Region Of Interest ◽  
Brain Parenchyma ◽  
Metabolic Derangement ◽  
Perfusion Computed Tomography ◽  
Asymptomatic Patients ◽  
Positron Emission ◽  
Pet Ct ◽  
Cellular Hypoxia

This study aimed to characterize hypoxic, but salvageable, tissue imaged by 18F-fluoromisonidazole (18F-FMISO), combining with perfusion-computed tomography (PCT) for regional cerebral blood flow (rCBF) measurement and metabolism by microdialysis (MD) in aneurysmal subarachnoidal hemorrhage (SAH) patients. 18F-FMISO positron-emission tomography (PET)/CT was performed within the period of possible vasospasm (day 6.8±3 after SAH) in seven SAH patients. In parallel, rCBF was determined within the MD region of interest (MD-ROI) ( n=5). The MD catheter was inserted into the brain parenchyma with highest risk for ischemia; extracellular levels of glutamate and energy metabolites were registered at time of PET and hourly for 10 days. Twelve-month outcome was evaluated. In asymptomatic patients ( n=3) no hypoxia was detected and glutamate levels were low (<10 mmol/L), whereas symptomatic patients had higher glutamate concentrations ( P<0.001). Increased 18F-FMISO uptake within the MD-ROI ( n=3) was related to higher glutamate levels, while rCBF was above the ischemic range. Hypoxia (increased 18F-FMISO uptake) was present in symptomatic patients and associated with relevant metabolic derangement of extracellular glutamate levels, whereas energy metabolism and rCBF were preserved. This technique has the potential to improve our understanding of the role of cellular hypoxia in aneurysmal SAH.

scholarly journals MRI and PET-CT Failed to Differentiate Between Hepatic Malignancy and Brucelloma

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Peter W Schreiber ◽  
Adrian Schmid ◽  
Stefania Fagagnini ◽  
Arne Kröger ◽  
Bart Vrugt ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Positron Emission Tomography Imaging ◽  
Resonance Imaging ◽  
Hepatic Malignancy ◽  
Local Complication ◽  
Tomography Imaging ◽  
Positron Emission ◽  
Resected Liver ◽  
Pet Ct ◽  
Polymerase Chain

Abstract Brucellosis is a common, worldwide zoonosis. Clinical presentation is protean and often goes unrecognized. Hepatic brucelloma is a rare local complication of chronic brucellosis. We report a case in which magnetic resonance imaging and positron emission tomography imaging prompted suspicion of a hepatic malignancy. Diagnosis was ultimately made by serology and polymerase chain reaction of resected liver tissue.

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