Immuno-PET for Clinical Theranostic Approaches

Bailly, Clément; Cléry, Pierre-François; Faivre-Chauvet, Alain; Bourgeois, Mickaël; Guérard, François; Haddad, Férid; Barbet, Jacques; Chérel, Michel; Kraeber-Bodéré, Françoise; Carlier, Thomas; Bodet-Milin, Caroline

doi:10.3390/ijms18010057

Cited by 57 publications

(56 citation statements)

References 77 publications

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“…The inclusion of noninvasive imaging of disease biomarkers in the design of clinical trials for antibody-based therapeutics can impact clinical outcomes by virtue of the ability of imaging to (i) identify patients who may be eligible for treatment with targeted therapies, (ii) inform the dosing of patients based on the in vivo expression levels of the biomarker, and (iii) evaluate response to treatment (17–19). There has been a surge of reports demonstrating the successful translation of immunoPET tracers in the cancer clinic (20–22). ImmunoPET allows the noninvasive evaluation of disease burden in vivo and facilitates the creation of a companion diagnostic agent to a therapeutic antibody.…”

Section: Introductionmentioning

confidence: 99%

Fc-Mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models

et al. 2018

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A critical benchmark in the development of antibody-based therapeutics is demonstration of efficacy in preclinical mouse models of human disease, many of which rely on immunodeficient mice. However, relatively little is known about how the biology of various immunodeficient strains impacts the in vivo fate of these drugs. Here we used immunoPET radiotracers prepared from humanized, chimeric and murine monoclonal antibodies against four therapeutic oncologic targets to interrogate their biodistribution in four different strains of immunodeficient mice bearing lung, prostate, and ovarian cancer xenografts. The immunodeficiency status of the mouse host as well as both the biological origin and glycosylation of the antibody contributed significantly to the anomalous biodistribution of therapeutic monoclonal antibodies in an Fc receptor-dependent manner. These findings may have important implications for the preclinical evaluation of Fc-containing therapeutics and highlight a clear need for biodistribution studies in the early stages of antibody drug development.

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Section: Introductionmentioning

confidence: 99%

Fc-Mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models

et al. 2018

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“…Monoclonal antibodies have exquisite selectivity for their target, and their applicability to immuno-PET has been appreciated for decades, particularly in the cancer field (6)(7)(8). However, the use of immuno-PET in IBD is currently limited to preclinical studies, in which T-cell infiltration into the colon of colitic animals has been demonstrated either directly by imaging the T HELPER cell marker CD4 (9) or indirectly by targeting the gut-homing integrin a 4 b 7 (10).…”

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confidence: 99%

Immuno-PET of Innate Immune Markers CD11b and IL-1β Detects Inflammation in Murine Colitis

et al. 2018

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Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. The diagnosis and monitoring of IBD are reliant on endoscopy, which is invasive and does not provide information on specific mediators. Symptom flare in IBD is associated with increased activation of innate immune pathways. Immuno-PET approaches have previously demonstrated the ability to detect colitis; however, a direct comparison of antibodies targeted to innate immune mediators and cells has not been done. We aimed to compare immuno-PET of antibodies to IL-1β and CD11b against standard 18 F-FDG and MRI approaches to detect colonic inflammation. Methods: Colonic concentrations of IL-1β and myeloperoxidase were determined by ELISA, and colonic infiltration by CD11b-positive CD3-negative innate immune cells was determined by flow cytometry and compared between healthy and dextran sodium sulphate-treated colitic mice. PET of 89 Zr-lα-IL-1β, 89 Zr-α-CD11b, and 18 F-FDG was compared by volume-of-interest analysis and with MRI by region-of-interest analysis. Imaging results were confirmed by ex vivo biodistribution analysis. Results: Colonic inflammation was associated with impaired colonic epithelial barrier permeability, increased colonic IL-1β and myeloperoxidase concentrations, and increased CD11b-positive CD3-negative innate immune cell infiltration into the colon. 89 Zr-α-IL-1β and 89 Zr-α-CD11b immuno-PET detected colonic inflammation, as did 18 F-FDG, and all PET tracers were more sensitive than MRI. Although 18 F-FDG volumes of interest correlated with colitis severity and a strong trend was observed with 89 Zr-α-IL-1β, no correlation was observed for 89 Zr-α-CD11b or MRI. 89 Zr-α-IL-1β was distributed mainly to the gastrointestinal tract, whereas 89 Zr-α-CD11b was distributed to more tissue types. Conclusion: Immuno-PET using antibodies directed to innate immune markers detected colonic inflammation, with 89 Zr-α-IL-1β providing a more tissue-specific signal than 89 Zr-α-CD11b. Development of these technologies for human subjects will potentially provide a less invasive approach than endoscopy for diagnosing and monitoring IBD. Detects Inflammation inβ Immuno-PET of Innate Immune Markers CD11b and IL-1 http://jnm.snmjournals.org/content/60/6/858 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

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“…Furthermore, it would be ideal to observe how the transplanted artificial ovary establishes on the recipient. Molecular imaging techniques such as positron emission tomography (PET) can be useful in detecting any abnormalities in graft if appropriate biomarkers are identified (Bailly et al, ). A previous study reported that 18F‐FDG PET/CT detected an infection in the implanted intracardiac device (Dejust, Guedec‐Ghelfi, Blanc‐Autrant, Lepers, & Morland, ).…”

Section: Evaluation and Monitoringmentioning

confidence: 99%

A new possibility in fertility preservation: The artificial ovary

Cho

Kim

Noh

et al. 2019

J Tissue Eng Regen Med

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Conventional fertility preservation methods such as oocyte or embryo cryopreservation are currently insufficient to treat including those patients with prepubertal cancer and premature ovarian failure. Ovarian tissue cryopreservation presents as an alternative but has limitations with a potential risk of reintroducing malignant cells in patients who recover from cancer, those of chemotherapy prior to tissue cryopreservation. The so called “artificial ovary” aims to resolve this issue by transplanting isolated follicles with or without a biological scaffold. The artificial ovary may also offer an effective alternative option for those who cannot benefit from traditional assisted reproductive techniques such as in vitro fertilisation. To date, in animal studies and human trial, the artificial ovary restored endocrine function, achieved in vivo follicular development, and resulted in successful pregnancies. However, development of a technique for higher follicular recovery rate and a more optimised design of delivery scaffold, better transplantation techniques to prevent postsurgical ischemia, and consideration for genetic safety are required for safer and consistent human clinical applications. Ideas from different transplantation surgeries (e.g., entire ovary, ovarian cortex, and transplantation with tissue‐engineered products) can be applied to enhance the efficacy of artificial ovarian transplantation. For the better application of artificial ovary, a deeper understanding of mechanical and biochemical properties of the ovary and folliculogenesis after cryopreservation, transplantation with or without scaffold, and development of sophisticated in vivo imaging techniques of transplanted artificial ovary need to precede its efficient clinical application.

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Immuno-PET for Clinical Theranostic Approaches

Cited by 57 publications

References 77 publications

Fc-Mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models

Fc-Mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models

Immuno-PET of Innate Immune Markers CD11b and IL-1β Detects Inflammation in Murine Colitis

A new possibility in fertility preservation: The artificial ovary

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