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Immuno-positron emission tomography (immunoPET) is a paradigmshifting molecular imaging modality combining the superior targeting specificity of monoclonal antibody (mAb) and the inherent sensitivity of PET technique. A variety of radionuclides and mAbs have been exploited to develop immunoPET probes, which has been driven by the development and optimization of radiochemistry and conjugation strategies. In addition, tumor-targeting vectors with a short circulation time (e.g., Nanobody) or with an enhanced binding affinity (e.g., bispecific antibody) are being used to design novel immunoPET probes. Accordingly, several immunoPET probes, such as 89 Zr-Df-pertuzumab and 89 Zr-atezolizumab, have been successfully translated for clinical use. By noninvasively and dynamically revealing the expression of heterogeneous tumor antigens, immunoPET imaging is gradually changing the theranostic landscape of several types of malignancies. ImmunoPET is the method of choice for imaging specific tumor markers, immune cells, immune checkpoints, and inflammatory processes. Furthermore, the integration of immunoPET imaging in antibody drug development is of substantial significance because it provides pivotal information regarding antibody targeting abilities and distribution profiles. Herein, we present the latest immunoPET imaging strategies and their preclinical and clinical applications. We also emphasize current conjugation strategies that can be leveraged to develop next-generation immunoPET probes. Lastly, we discuss practical considerations to tune the development and translation of immunoPET imaging strategies.
Immuno-positron emission tomography (immunoPET) is a paradigmshifting molecular imaging modality combining the superior targeting specificity of monoclonal antibody (mAb) and the inherent sensitivity of PET technique. A variety of radionuclides and mAbs have been exploited to develop immunoPET probes, which has been driven by the development and optimization of radiochemistry and conjugation strategies. In addition, tumor-targeting vectors with a short circulation time (e.g., Nanobody) or with an enhanced binding affinity (e.g., bispecific antibody) are being used to design novel immunoPET probes. Accordingly, several immunoPET probes, such as 89 Zr-Df-pertuzumab and 89 Zr-atezolizumab, have been successfully translated for clinical use. By noninvasively and dynamically revealing the expression of heterogeneous tumor antigens, immunoPET imaging is gradually changing the theranostic landscape of several types of malignancies. ImmunoPET is the method of choice for imaging specific tumor markers, immune cells, immune checkpoints, and inflammatory processes. Furthermore, the integration of immunoPET imaging in antibody drug development is of substantial significance because it provides pivotal information regarding antibody targeting abilities and distribution profiles. Herein, we present the latest immunoPET imaging strategies and their preclinical and clinical applications. We also emphasize current conjugation strategies that can be leveraged to develop next-generation immunoPET probes. Lastly, we discuss practical considerations to tune the development and translation of immunoPET imaging strategies.
Objective: Immuno-positron emission tomography (iPET) combines the sensitivity of the PET imaging technique and the targeting specificity of radio-labelled monoclonal antibodies (mAb). Its first clinical applications in humans were described in the late 1990s, and several pathologies have benefitted from this molecular imaging modality since then. Our scope was to assess current clinical applications of immuno-PET in patients with lymphoma. Therefore, a systematic review of the published literature was performed. Methods: PubMed/Medline and Scopus databases were independently searched by two nuclear medicine physicians, to identify studies describing the clinical use of immuno-PET in patients with lymphoma. Methodological quality of the included articles was assessed by using the Quality Assessment of Diagnostic Accuracy Studies criteria. The studies were then analyzed concerning the molecular target of interest. Results: The initial search yielded 1407 articles. After elimination of duplicates, 1339 titles/abstracts were evaluated. Only two articles were found to comply with the inclusion criteria and two more were found during the cross-reference check. Among the four included articles, three described the use of 89Zr-labelled antibodies targeting CD20+ relapsed/refractory B-cell lymphomas and one concerned the use of 68Ga-labelled mAb targeting CXCR4 in patients with non-Hodgkin lymphomas. Conclusions: Very limited literature data are currently available on the clinical use of iPET in patients with lymphoma. This technique is encountering obstacles in its wider use, possibly because of the need of specific facilities, unfavorable dosimetry, and unclear correlation of immuno-tracer biodistribution with patients’ clinical and tumors’ molecular characteristics. However, iPET may represent a useful tool to non-invasively visualize the heterogenous individual immunological environment, thus potentially guiding treatment-planning in lymphoma patients, and hence deserves further exploitation.
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