First-in-human imaging of nanoparticle entrapped docetaxel (CPC634) in patients with advanced solid tumors using 89Zr-Df-CPC634 PET/CT.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3093-3093 ◽  
Author(s):  
Iris H.C. Miedema ◽  
Gerben J.C. Zwezerijnen ◽  
Daniela E. Oprea-Lager ◽  
Henk M.W. Verheul ◽  
Danielle J. Vugts ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Prolonged Exposure ◽  
Reticuloendothelial System ◽  
Whole Body ◽  
Tracer Injection ◽  
Epr Effect ◽  
Focal Uptake ◽  
Pet Ct ◽  
Tumor Retention

3093 Background: CPC634 is a nanoparticle entrapping docetaxel designed to improve tumor accumulation and tolerability compared to conventionally administered docetaxel by taking advantage of the presumed enhanced permeability and retention (EPR) effect. In vivo imaging with zirconium-89 (89Zr)-desferal (Df)-CPC634 will provide valuable information on its biodistribution and will quantify tumor retention. Methods: Patients with solid tumors not amenable to standard therapy received 37 MBq, 0.1-2mg of 89Zr-Df-CPC634 tracer and whole body PET/CT scans were obtained at 2, 24 and 96h post-injection (p.i.). Patients were administered CPC634 (60mg/m2) two weeks later followed by a second tracer injection and scans at 24 and 96h p.i. Biodistribution was quantified by delineating organs of interest and calculating mean %ID/kg. Visual tumor retention was defined as focal uptake in tumor lesions exceeding local background and quantified as standardized uptake peak values (SUVpeak) in volumes of interest. Results: Five patients were included. Biodistribution of 89Zr-Df-CPC634 showed significant retention in healthy liver, and spleen compared to lung (respectively 2.54, 1.61 and 0.56 mean %ID/kg at 96h p.i.), supporting apparent opsonization of nanoparticles in cells of the reticuloendothelial system. Visual retention was observed in 16/37 evaluable tumor lesions with the highest intensity at 96h p.i, compatible with the assumed EPR effect. Tumor retention showed intra- and interpatient heterogeneity, with a mean %ID/kg of 3.43 [1.14-9.32]. Pre-administering unlabeled CPC634 did not change the mean tumor retention of 89Zr-Df-CPC634 (at 96h p.i. mean 3.50 %ID/kg [1.64-9.97]), however, four additional lesions were visible in comparison to tracer only. Conclusions: The biodistribution of 89Zr-Df-CPC634 was consistent with a prolonged exposure of nanoparticle containing docetaxel. 89Zr-Df-CPC634 showed high retention in tumors confirming the EPR effect of these nanoparticle in humans, and supporting their further development for tumor targeting of therapeutic agents. A Phase II efficacy study in platinum resistant ovarian cancer (NTC03742713) is currently ongoing. Clinical trial information: NCT03712423.

scholarly journals Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64–labeled daratumumab

2020 ◽  
Vol 4 (20) ◽  
pp. 5194-5202
Author(s):  
Amrita Krishnan ◽  
Vikram Adhikarla ◽  
Erasmus K. Poku ◽  
Joycelynne Palmer ◽  
Ammar Chaudhry ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity And Specificity ◽  
Imaging Techniques ◽  
Phase 1 ◽  
Whole Body ◽  
Human Antibody ◽  
Whole Body Imaging ◽  
Positron Emission ◽  
Pet Ct

Abstract 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n = 3), 10 (n = 3), 45 (n = 3), or 95 mg (n = 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.

scholarly journals Early-Dynamic Positron Emission Tomography (PET)/Computed Tomography and PET Angiography for Endoleak Detection After Endovascular Aneurysm Repair

2017 ◽  
Vol 24 (3) ◽  
pp. 421-424 ◽  
Author(s):  
Robert Drescher ◽  
Falk Gühne ◽  
Martin Freesmeyer
Keyword(s):  
Computed Tomography ◽  
Positron Emission Tomography ◽  
Endovascular Aneurysm Repair ◽  
Emission Tomography ◽  
Whole Body ◽  
Dynamic Pet ◽  
Tracer Injection ◽  
Positron Emission ◽  
Pet Ct ◽  
Aneurysm Repair

Purpose: To propose a positron emission tomography (PET)/computed tomography (CT) protocol including early-dynamic and late-phase acquisitions to evaluate graft patency and aneurysm diameter, detect endoleaks, and rule out graft or vessel wall inflammation after endovascular aneurysm repair (EVAR) in one examination without intravenous contrast medium. Technique: Early-dynamic PET/CT of the endovascular prosthesis is performed for 180 seconds immediately after intravenous injection of F-18-fluorodeoxyglucose. Data are reconstructed in variable time frames (time periods after tracer injection) to visualize the arterial anatomy and are displayed as PET angiography or fused with CT images. Images are evaluated in view of vascular abnormalities, graft configuration, and tracer accumulation in the aneurysm sac. Whole-body PET/CT is performed 90 to 120 minutes after tracer injection. Conclusion: This protocol for early-dynamic PET/CT and PET angiography has the potential to evaluate vascular diseases, including the diagnosis of complications after endovascular procedures.

VP69 Mapping Brazilian Nuclear Medicine Installed Capacity And Perspectives

2017 ◽  
Vol 33 (S1) ◽  
pp. 180-181
Author(s):  
Lorena Pozzo ◽  
Evelinda Trindade
Keyword(s):  
Nuclear Medicine ◽  
Regional Analysis ◽  
Reticuloendothelial System ◽  
Myocardial Scintigraphy ◽  
National Commission ◽  
The South ◽  
North East ◽  
Pet Ct ◽  
Nuclear Medicine Procedures

INTRODUCTION:Guidelines compliance, with a priori non-invasive and earlier tests and interventions, depends on access. This study investigates the Brazilian Unified Health System (SUS) outpatient access to nuclear medicine procedures through SUS data comparison with those from the National Commission of Nuclear Energy (CNEN: Comissão Nacional de Energia Nuclear).METHODS:Data provided by the SUS outpatient database (SIA-DATASUS) regarding procedures performed from 2013 to 2016 was compared with data from institutions (Nuclear Medicine Services and Cyclotron Facilities) and radioprotection supervisors with numbers certified by CNEN.RESULTS:CNEN has authorized 420 nuclear medicine institutions (.20 per million inhabitants) and certified 294 radioprotection supervisors (.14 per million inhabitants), and 1.4 services per supervisor. There are 457 graduated professionals qualified for radioactive sources preparation, use and handling for diagnostic and therapeutic radiopharmaceuticals (.9 professionals / installation). During the last four years, 08 new nuclear medicine facilities were authorized by CNEN. The number of nuclear medicine procedures performed slightly increased in the South, but remained constant in other regions. Annual SUS reimbursements increased by 21.2 percent on average for the 03 PET/CT (Positron emission tomography–computed tomography) adopted procedures: regional analysis showed the Central-West as the highest growth area (70.8 percent), compared to the South (53.4 percent), North-East region (30.8 percent), and the South-East (5 percent). Currently, thirteen Cyclotron Facilities operate in Brazil: South-East (six), South (three), North-East (three) and Central-West (one). Some nuclear medicine procedures largely outnumber the average increase: for example, reticuloendothelial system scintigraphy (513.9 percent), gastric transit scintigraphy (112.8 percent), and thyroid screening with suppression/stimulation test (100.6 percent). However, myocardial scintigraphy (stress and rest) and bone scintigraphy with or without blood flow still correspond to 82 percent of total nuclear medicine in vivo procedures.CONCLUSIONS:Regional disparity is quantitatively depicted in Brazil and reflects access to SUS nuclear medicine procedures. This denotes a potential for improvements related to nuclear medicine areas, for example developments concerning new PET/CT coverage, new radiopharmaceuticals research, and national and international training.

scholarly journals Preclinical Evaluation and Pilot Clinical Study of 18F-AlF-labeled FAPI-Tracers for PET Imaging of Cancer Associated Fibroblasts

2021 ◽  
Author(s):  
Kongzhen Hu ◽  
Junqi Li ◽  
Lijuan Wang ◽  
Yong Huang ◽  
Li Li ◽  
...  
Keyword(s):  
Nasopharyngeal Cancer ◽  
High Specificity ◽  
Whole Body ◽  
Cancer Associated Fibroblasts ◽  
Primary Tumors ◽  
Preclinical Evaluation ◽  
Biodistribution Studies ◽  
Pet Ct

Abstract Background The recent development of many different types of radiotracers that target the fibroblast activation protein (FAP) has been promising for tumor diagnosis. Here, we set out to develop 18F-labeled FAP tracers for cancer-associated fibroblast imaging and evaluated the potential of these tracers for clinical application. Methods The non-radioactive reference compounds and labeling precursors were synthesized using organic chemistry and the binding affinities were identified using surface plasmon resonance. Both radioligands (18F-P-FAPI and 18F-FAPI-42) were produced in an automated manner via complexation of Al18F. For in vitro characterization of 18F-P-FAPI and 18F-FAPI-42, we conducted studies to determine the partition coefficients, stability, cellular uptake, internalization, and efflux. In vivo biodistribution studies and microPET imaging of 18F-P-FAPI and 18F-FAPI-42, in comparison to 68Ga-FAPI-04, were conducted on the A549-FAP tumor bearing mice. Finally, one nasopharyngeal cancer patient underwent whole-body PET/CT after being injected with 18F-P-FAPI. Results Both 18F-P-FAPI and 18F-FAPI-42 were successful prepared with high specificity, rapid internalization, and potent affinity binding toward FAP. Compared to 18F-FAPI-42, 18F-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Furthermore, in vivo studies of 18F-P-FAPI in the A549-FAP tumor model indicated a higher tumor uptake than 18F-FAPI-42 and 68Ga-FAPI-04. An initial diagnostic application in patient with nasopharyngeal cancer, 18F-P-FAPI and 18F-FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. Conclusion The radiofluorinated FAP-ligands demonstrated promising characteristics in their preclinical evaluation, and the feasibility of cancer-associated fibroblasts imaging was demonstrated using PET studies.

scholarly journals The diagnostic significance of breast incidentalomas detected on whole-body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

2015 ◽  
Vol 01 (02) ◽  
pp. 092-096
Author(s):  
Shelly Sharma ◽  
Ankur Pruthi
Keyword(s):  
Breast Cancer ◽  
Computed Tomography ◽  
Emission Tomography ◽  
Whole Body ◽  
Diagnostic Significance ◽  
Focal Uptake ◽  
Positron Emission ◽  
Pet Ct ◽  
The Mean ◽  
Fdg Pet Ct

ABSTRACT Objective: The objective of this study was to establish the diagnostic significance of breast incidentalomas detected on whole-body fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Materials and Methods: We retrospectively analyzed the data of 3868 patients who underwent 18F FDG PET/CT at our institution, for the presence of hypermetabolic focus in the breasts. Patients with known breast cancer or with the previous history of breast cancer were excluded from the study. Ten out of remaining 3868 patients had abnormal focal uptake in the breast. We, therefore, enrolled these 10 patients with histopathology confirmation in this study. Results: Among all 3868 patients, 10 (0.25%) patients demonstrated incidental focal uptake in breast parenchyma. All of these 10 patients were females. Histopathology examination confirmed malignancy in 8 out of 10 patients (80%), these included invasive ductal cancer in 4 patients, non-Hodgkin's lymphoma in 2 patients, and metastasis from rectal cancer and endometrial cancer, respectively, in 2 patients. Of the 10 patients, 2 (20%) had lesions that were confirmed to be benign. Both of these were proven to be fibroadenomas. The mean maximum standardized uptake value (SUVmax) on FDG-PET/CT scans was 1.35 ± 1.2 in the benign cases versus 3.8 ± 1.83 in the malignant cases. This difference was statistically insignificant (P = 0.056). All malignant lesions had SUVmax 2.0 or greater. The mean size differed significantly between the benign and malignant groups (2.55 ± 0.63 vs. 1.31 ± 0.44 cm) (P = 0.005) with benign lesions being bigger in size. Conclusion: Unexpected focal areas of hypermetabolic activity discovered in the breast at the time of PET/CT are associated with a high likelihood of malignancy in as many as 80% of cases. Therefore, any suspicious activity discovered in the breast on PET/CT should be evaluated until a diagnosis is found.

scholarly journals 64cu-DOTA-Anti-CD33 PET-CT Imaging for Acute Myeloid Leukemia and Image-Guided Treatment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2747-2747 ◽  
Author(s):  
Srideshikan Sargur Madabushi ◽  
Darren Zuro ◽  
Jamison Brooks ◽  
Bijender Kumar ◽  
Liliana E Parra ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Treatment Plan ◽  
Ct Imaging ◽  
Whole Body ◽  
Non Invasive ◽  
Image Guided ◽  
Biodistribution Studies ◽  
Pet Ct ◽  
Total Marrow Irradiation

Abstract Introduction: Acute myeloid leukemia (AML) is a highly aggressive form of leukemia that results a poor survival outcome. Currently, diagnosis and prognosis are based on invasive single-point bone marrow biopsies (iliac crest). Although non-invasive positron emission tomography (PET) imaging has been developed for almost all solid tumors and some hematological malignancies, there is currently no non-invasive imaging specific to AML available, representing an unmet clinical need. About 85% of AML cells express CD33, and expression levels of CD33 has been correlated with poor survival outcomes (Pollard et al., Blood (2012)), making it an ideal candidate for immuno-PET. Therefore, our primary goal is to develop anti-CD33 immuno-PET for detecting CD33+ AML. The secondary goal is to assess the feasibility of CD33 PET image-guided external beam targeted radiation delivery in combination with chemotherapy (AraC). Methods: Murine anti-human CD33 monoclonal antibody clone p67.6 was conjugated to DOTA and radiolabeled with Cu-64 for imaging studies. In vivo PET-CT imaging and bio distribution of 64Cu-DOTA-anti-CD33 in vivo was carried out in NSG mice bearing CD33+ (MV4-11, HL60) AML cells. CD33-negative MM1s cells (multiple myeloma) were used as negative control. The AML and MM bearing mice were injected with 64Cu-DOTA-anti-CD33 (100 µCi/10 µg) and serial PET imaged at 24-48 h. We developed a functional total marrow irradiation (fTMI) treatment, where mice received total marrow irradiation (TMI) (2 Gy) and boost radiation (2 Gy) to regions with increased CD33 activity, followed by 2 days of AraC (40 mg/kg) and 24h later a bone marrow transplant. Furthermore, a humanized anti-human CD33 monoclonal antibody was generated and tested for immunogenicity against CD33 in AML cell lines and patient samples for future clinical studies. Results: PET-CT imaging and biodistribution studies of 64Cu-DOTA-anti-CD33 clearly indicates a CD33+ PET signal in the femur, tibia, humerus joints, L spine and spleen in AML-bearing mice, but not in multiple myeloma-bearing mice or in cold anti-CD33-DOTA treated leukemic mice (Figure 1A and B). Our new imaging method was able to detect CD33+ AML with a favorable sensitivity (71.4%) and specificity (100%). Based on detailed whole-body 3D imaging and validated with biodistribution studies, we discovered preferential regions in the skeletal system with differential CD33 activity, indicating the spatial heterogeneity of AML. CD33+ PET intensity was observed in the following descending order: femur≥lspine>humerus>tibia (Figure 1C). Next, using the PET-CT images, we targeted these CD33-active regions using the fTMI treatment plan. We have developed a unique irradiation system which allows targeting only skeletal tissues while sparing major organs like gut, lung and liver, unlike conventional total body irradiation (TBI). This approach will also provide an opportunity to escalate doses to specific regions in the body without damaging other unintended targets. The fTMI (2 Gy TMI and 2 Gy boost) treatment plan increased the medial survival of the mice to 43 days versus that of untreated control mice (26 days) or AraC treated mice (33 days) Figure(1D). Since the preclinical study was carried out using murine anti-CD33 antibody clone p67.6, we further tested the newly generated humanized anti-human-CD33 monoclonal antibody. This humanized antibody detects CD33 in both AML cell lines and human patient sample (Fig 1E). Conclusion: This study is the first to use an anti-CD33 monoclonal antibody for non-invasive immuno-PET-based imaging for AML detection, showing high sensitivity and specificity. This whole body imaging may be useful for AML diagnosis not only in the entire skeletal system, but also in the extramedullary organs, and for longitudinal monitoring of treatment response. Unlike conventional TBI, Image-guided fTMI along with conventional chemotherapy may result in an improved prognosis, as unintended major organs are spared from radiation. Disclosures Vallera: GT Biopharma: Consultancy, Research Funding. Stein:Celgene: Speakers Bureau; Amgen Inc.: Speakers Bureau.

scholarly journals [18F]FDG uptake of the normal spinal cord in PET/MR imaging: Comparison with PET/CT imaging

2020 ◽  
Author(s):  
Marco Aiello ◽  
Vincenzo Alfano ◽  
Elena Salvatore ◽  
Carlo Cavaliere ◽  
Marco Picardi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Bone Marrow Involvement ◽  
Whole Body ◽  
Longitudinal Distribution ◽  
Tracer Injection ◽  
Fdg Uptake ◽  
Bone Marrow Uptake ◽  
Pet Ct ◽  
Custom Made

Abstract Background The lack of visualization of the spinal cord hinders the evaluation of [18F]Fluoro-deoxy-glucose (FDG) uptake of the spinal cord in PET/CT. By exploiting the capability of MRI to precisely outline the spinal cord, we performed a retrospective study aimed to define normal pattern of spinal cord [18F]FDG uptake in PET/MRI.Methods Forty-one patients with lymphoma without clinical or MRI signs of spinal cord or bone marrow involvement underwent simultaneous PET and MRI acquisition using Siemens Biograph mMR after injection of 3.5 MBq/kg body weight of [18F]FDG for staging purposes. Using a custom-made software, we placed ROIs of 3 and 9 mm in diameter in spinal cord, lumbar CSF and vertebral marrow that were identified on MRI at 5 levels (C2, C5, T6, T12 and L3). The SUVmax, SUVmean and the SUVmax and SUVmean normalized (NSUVmax and NSUVmean) to the liver were measured. For comparison, the same ROIs were placed in PET-CT images obtained immediately before the PET-MRI acquisition following the same tracer injection.Results On PET/MRI using the 3 mm ROI the following average (all level excluding L3) spinal cord median (1st and 3rd quartile) values were measured:SUVmean1.68 (1.39 and 1.83), SUVmax1.92(1.60 and 2.14), NSUVmean1.18(0.93 and 1.36), NSUVmax1.27(1.01 and 1.33). Using the 9 mm ROI the corresponding values were: SUVmean1.41 (1.25-1.55), SUVmax2.41(2.08 and 2.61), NSUVmean0.93 (0.79 and 1.04), NSUVmax1.28(1.02 and 1.39).Using the 3 mm ROI the highest values of PET-MRI SUVmax, SUVmean, NSUVmax and NSUVmean were consistently observed at C5 and the lowest at T6. Using a 9 mm ROI the highest values were consistently observed at C5 and the lowest at T12 or T6. The spinal cord [18F]FDG-uptake values correlated with bone marrow uptake at the same level, especially in case of NSUVmax. Comparison with PET-CT data revealed that the average SUVmax and SUVmean of the spinal cord were similar in PET-MRI and PET-CT. However, the average NSUVmax and NSUVmean of the spinal cord were higher (range 21% - 47%) in PET-MRI than in PET-CT. Conclusions Using a whole-body protocol we defined the maximum and mean [18F]FDG uptake of the normal spinal cord in PET/MRI. While the observed values show the expected longitudinal distribution, they appear to be higher than those measured in PET/CT. Normalization of the SUVmax and SUVmean of the spinal cord to the liver radiotracer uptake could help in multi-institutional comparisons and studies.

scholarly journals A Prospective Comparison of [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT in Patients With Various Cancers

2021 ◽  
Author(s):  
Kongzhen Hu ◽  
Lijuan Wang ◽  
Hubing Wu ◽  
Shun Huang ◽  
Ying Tian ◽  
...  
Keyword(s):  
Standardized Uptake Value ◽  
Tumor Detection ◽  
Whole Body ◽  
Acquisition Time ◽  
Bone Lesions ◽  
Tumor Uptake ◽  
Detection Ability ◽  
Pet Ct ◽  
High Level

Abstract Purpose: [18F]FAPI-42 is a new fibroblast activation protein (FAP) specific tracer used for cancer imaging. Here, we describe the in vivo evaluation of [18F]FAPI-42 and compared intra-individual biodistribution, tumor uptake, and detection ability to [68Ga]Ga-FAPI-04.Methods: A total of 22 patients with various types of cancer received [18F]FAPI-42 whole-body positron emission tomography/computed tomography (PET/CT). Among them, 4 patients underwent PET/CT scans, including an early dynamic 20-min, static 1-hour and static 2-hours. The in vivo biodistribution in normal organs and tumor uptake were semi-quantitatively evaluated using the standardized uptake value (SUV) and tumor-to-background ratio (TBR). Furthermore, both [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT were performed in 12 patients to compare biodistribution, tumor uptake, and tumor detection ability.Results: [18F]FAPI-42 uptake in the tumors was rapid and reached a high level with an average SUVmax of 15.8 at 18 minutes, which stayed at a similarly high level to 2 hours. The optimal image acquisition time for [18F]FAPI-42 was determined to be 1 hour post injection. Compared to [68Ga]Ga-FAPI-04, [18F]FAPI-42 had a higher uptake in the parotid, salivary gland, thyroid, and pancreas (P < 0.05). For tumor detection, [18F]FAPI-42 had a high uptake and could be clearly visualized in the lesions. [18F]FAPI-42 and [68Ga]Ga-FAPI-04 showed the same detectability for 144 positive lesions. In addition, [18F]FAPI-42 had a higher SUVmax in liver and bone lesions (P < 0.05) and higher TBRs in liver, bone, lymph node, pleura and peritonea lesions (all P < 0.05).Conclusion: The present study demonstrates that [18F]FAPI-42 is a good tracer for imaging malignant tumors and exhibited comparable lesion detectability to [68Ga]Ga-FAPI-04. The 1-hour scan is an appropriate time for tumor detection and is superior to the early 10-min scan for the detection of small lesions.Trial registration Chinese Clinical Trial Registry (ChiCTR2100045757)

scholarly journals First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e002926
Author(s):  
Shujing Wang ◽  
Hua Zhu ◽  
Yingjie Li ◽  
Jin Ding ◽  
Feng Wang ◽  
...  
Keyword(s):  
Standardized Uptake Value ◽  
Tumor Xenograft ◽  
Whole Body ◽  
Death Receptor 5 ◽  
High Uptake ◽  
Surgical Operation ◽  
Expression Levels ◽  
Pet Ct ◽  
Gi Cancers

BackgroundDeath receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers.MethodsBalb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent 18F-FDG and 89Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope.ResultsPreclinical studies showed that 89Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of 89Zr-CTB006 with a mean maximum standardized uptake value (SUVmax) of 6.63±3.29 (range 1.8–13.8). Tumor tissue was obtained from 18 patients, and 89Zr-CTB006 uptake in patients with RNAscope scores of 3–4 was significantly higher than that in patients with scores of 0–2. An SUVmax of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively.Conclusions89Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression.

Kinetics, Redistribution And Fate Of Indium-111-Labelled-Platelets In Patients With Aortic Aneurysms

1981 ◽  
Author(s):  
A duP Heyns ◽  
M G Lötter ◽  
P N Badenhorst ◽  
F de Kock ◽  
H Pieters ◽  
...  
Keyword(s):  
Imaging System ◽  
Reticuloendothelial System ◽  
Aortic Aneurysms ◽  
Whole Body ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Normal Limits ◽  
Geometrical Mean ◽  
Indium 111

Platelets of 7 patients with abdominal aortic aneurysms were labelled with In-lll-oxine prior to surgery. The platelets were reinjected with the patient positioned under a scintillation camera with a computer assisted imaging system. Images were acquisitioned daily, areas of interest selected with the computer, organ radioactivity- quantitated with a geometrical mean method and expressed as a percentage of whole body radioactivity. Platelet survival (PS) in the circulation was determined, and disappearance curves fitted to a gamma function “multiple hit” model.Mean PS was shorthened to 143,2 ± 47h (normal 232<17); the dissappearance curves were exponential in all but the two patients who had PS within normal limits. The surgically removed aneurysms were dissected and radioactivity of different layers measured. In-111-activity was confined to the superficial layers of the aneurysm.These techniques allow quantitative studies of the in vivo distribution of labelled platelets. Platelets are deposited in the aneurysms, this shortens PS, the disappearance curves become exponential, and the major sites of deposition of In-111-activity are in the liver and spleen. This indicates that although platelets are damaged and deposited in the aneurysm, the reticuloendothelial system remains a major site of platelet sequestration.

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