A comparative evaluation of the chelators H 4 octapa and CHX-A″-DTPA with the therapeutic radiometal 90 Y

Price, Eric W.; Edwards, Kimberly J.; Carnazza, Kathryn E.; Carlin, Sean D.; Zeglis, Brian M.; Adam, Michael J.; Orvig, Chris; Lewis, Jason S.

doi:10.1016/j.nucmedbio.2016.06.004

Cited by 26 publications

(18 citation statements)

References 34 publications

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“…This antibody has been labeled with 177 Lu, 64 Cu, 111 In,Thorium-227 ( 227 Th), Rhenium-188 ( 188 Re), Yttrium-90 ( 90 Y), and Iodine-131 ( 131 I). 34 –37,45,63 –66…”

Section: Targeting Of Her2 For Radionuclide Therapymentioning

confidence: 99%

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Targeting HER2 in Nuclear Medicine for Imaging and Therapy

2018

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Since its discovery, the human epidermal growth factor 2 (HER2) has been extensively studied. Presently, there are 2 standard diagnostic techniques to assess HER2 status in biopsies: immunohistochemistry and fluorescence in situ hybridization. While these techniques have played an important role in the treatment of patients with HER2-positive cancer, they both require invasive biopsies for analysis. Moreover, the expression of HER2 is heterogeneous in breast cancer and can change over the course of the disease. Thus, the degree of HER2 expression in the small sample size of biopsied tumors at the time of analysis may not represent the overall status of HER2 expression in the whole tumor and in between tumor foci in the metastatic setting as the disease progresses. Unlike biopsy, molecular imaging using probes against HER2 allows for a noninvasive, whole-body assessment of HER2 status in real time. This technique could potentially select patients who may benefit from HER2-directed therapy and offer alternative treatments to those who may not benefit. Several antibodies and small molecules against HER2 have been labeled with different radioisotopes for nuclear imaging and/or therapy. This review presents the most recent advances in HER2 targeting in nuclear medicine focusing on preclinical and clinical studies.

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“…This antibody has been labeled with 177 Lu, 64 Cu, 111 In,Thorium-227 ( 227 Th), Rhenium-188 ( 188 Re), Yttrium-90 ( 90 Y), and Iodine-131 ( 131 I). 34 –37,45,63 –66…”

Section: Targeting Of Her2 For Radionuclide Therapymentioning

confidence: 99%

“…Also, both radiopharmaceuticals significantly inhibited tumor growth (tumor with 300 mm 3 of volume after 36 days PI) compared to the control group (tumor with 1000 mm 3 of volume after 36 days PI). 34…”

Section: Targeting Of Her2 For Radionuclide Therapymentioning

confidence: 99%

Targeting HER2 in Nuclear Medicine for Imaging and Therapy

2018

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“…In general, when the average number of BFCs per protein (N) increases the immunoreactivity of the obtained product decreases. It is possible to determine “N” by calculating the difference in mass between the mass of the conjugates and the native mAb [52,53]. The mass of the conjugates was measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Figure 2b) and the average number of DOTA(SCN) molecules per molecule of cG250 was then calculated.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Radiolabeled Girentuximab In Vitro and In Vivo

et al. 2018

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Girentuximab (cG250) targets carbonic anhydrase IX (CAIX), a protein which is expressed on the surface of most renal cancer cells (RCCs). cG250 labeled with 177Lu has been used in clinical trials for radioimmunotherapy (RIT) of RCCs. In this work, an extensive characterization of the immunoconjugates allowed optimization of the labeling conditions with 177Lu while maintaining immunoreactivity of cG250, which was then investigated in in vitro and in vivo experiments. cG250 was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA(SCN)) by using incubation times between 30 and 90 min and characterized by mass spectrometry. Immunoconjugates with five to ten DOTA(SCN) molecules per cG250 molecule were obtained. Conjugates with ratios less than six DOTA(SCN)/cG250 had higher in vitro antigen affinity, both pre- and postlabeling with 177Lu. Radiochemical stability increased, in the presence of sodium ascorbate, which prevents radiolysis. The immunoreactivity of the radiolabeled cG250 tested by specific binding to SK-RC-52 cells decreased when the DOTA content per conjugate increased. The in vivo tumor uptake was < 10% ID/g and independent of the total amount of protein in the range between 5 and 100 µg cG250 per animal. Low tumor uptake was found to be due to significant necrotic areas and heterogeneous CAIX expression. In addition, low vascularity indicated relatively poor accessibility of the CAIX target.

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“…While CHX-A″-DTPA and DOTA show good stability, labeling generally requires mild heating (40–60 °C) and long reaction times (30–60 min). Other new chelators, 5p-C-NETA and H 4 octapa have also been developed with promising stabilities for yttrium radiolabeling of Abs [ 127 , 128 ].…”

Section: Radionuclides For Antibody Imagingmentioning

confidence: 99%

Development of Antibody Immuno-PET/SPECT Radiopharmaceuticals for Imaging of Oncological Disorders—An Update

Dewulf

Adhikari

Vangestel

et al. 2020

Cancers

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Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are molecular imaging strategies that typically use radioactively labeled ligands to selectively visualize molecular targets. The nanomolar sensitivity of PET and SPECT combined with the high specificity and affinity of monoclonal antibodies have shown great potential in oncology imaging. Over the past decades a wide range of radio-isotopes have been developed into immuno-SPECT/PET imaging agents, made possible by novel conjugation strategies (e.g., site-specific labeling, click chemistry) and optimization and development of novel radiochemistry procedures. In addition, new strategies such as pretargeting and the use of antibody fragments have entered the field of immuno-PET/SPECT expanding the range of imaging applications. Non-invasive imaging techniques revealing tumor antigen biodistribution, expression and heterogeneity have the potential to contribute to disease diagnosis, therapy selection, patient stratification and therapy response prediction achieving personalized treatments for each patient and therefore assisting in clinical decision making.

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A comparative evaluation of the chelators H 4 octapa and CHX-A″-DTPA with the therapeutic radiometal 90 Y

Cited by 26 publications

References 34 publications

Targeting HER2 in Nuclear Medicine for Imaging and Therapy

Targeting HER2 in Nuclear Medicine for Imaging and Therapy

Evaluation of Radiolabeled Girentuximab In Vitro and In Vivo

Development of Antibody Immuno-PET/SPECT Radiopharmaceuticals for Imaging of Oncological Disorders—An Update

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