ImmunoPET: Concept, Design, and Applications

Abstract

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.

Antibody–Drug Conjugates for Cancer Therapy

“…These factors are vital in delivering a safe dose while maximizing antitumor effects as well as providing insight into the in vivo properties of these drugs [ 169 , 170 ]. Both SPECT and PET imaging of ADCs have been reported in preclinical and human studies, with the superior resolution and quantitative capabilities of immunoPET showing particular promise [ 171 ]. The majority of immunoPET studies with intact ADCs have utilized Zirconium-89 ( 89 Zr) due to its suitability for radiochemistry and long half-life (T1/2 = 78.4 h) which facilitates optimal imaging of the biodistribution of intact mAbs.…”

Imaging of cell-based therapy using 89Zr-oxine ex vivo cell labeling for positron emission tomography

“…Therefore, PET imaging using 89 Zr has been gaining attention, and the usefulness of 89 Zr-immunoPET, in which antibodies or antibody fragments are labeled with 89 Zr (e.g. 89 Zr-labeled anti-PD-1/PD-L1 antibody), for imaging human patients has been evaluated [36][37][38][39]. For the specific task of tracking adoptively transferred cells for multiple days with relatively high resolution, cells to be tracked are labeled with 89 Zr-oxine and imaged by PET [40,41].…”

ImmunoPET in Multiple Myeloma—What? So What? Now What?

“…ImmunoPET perfectly fits in this strategy. It has previously demonstrated its usefulness in precisely mapping lesion profiles at the molecular level, identifying the available target densities, exploring mAbs targeting capabilities and distribution patterns, assessing treatment response, and predicting adverse events [7,79,[81][82][83]. Optimal dosing could even be achieved through sequential imaging.…”

“…ImmunoPET also opens the door to radioimmunotherapy (RIT). Indeed, it provides a useful theranostic companion for targeting assessment and for dosimetric purposes before the administration of therapeutic radioimmunoconjugates [7,79,82]. RIT exploits the immune protein as a carrier to deliver a high dose of therapeutic radiation to tumour cells and limit exposure of normal cells.…”