Current Perspectives on 89Zr-PET Imaging

Yoon, Joon-Kee; Park, Bok-Nam; Ryu, Eun-Kyoung; An, Young‐Sil; Lee, Su Jin

doi:10.3390/ijms21124309

Cited by 90 publications

(70 citation statements)

References 115 publications

(158 reference statements)

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“…However, imaging several days after tracer injection is inconvenient for the patient and makes it difficult to assess more rapid changes in the density of the target, as the tumor uptake on PET reflects the average density of the target during a period of 5 to 7 days. Furthermore, long-lived radioisotopes, such as 89 Zr, cause a several-fold higher radiation exposure to normal organs than 18 F ( 87 ). However, new total-body PET scanners will make it feasible to acquire PET scans with 89 Zr-labeled radiotracers ~30 days after injection, and could allow for the radioactivity administered to be reduced by a factor of 40 ( 88 – 90 ).…”

Section: Considerations For the Development And Use Of Pd-(l)1 Pet Tracersmentioning

confidence: 99%

Molecular Imaging and the PD-L1 Pathway: From Bench to Clinic

et al. 2021

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Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors target the important molecular interplay between PD-1 and PD-L1, a key pathway contributing to immune evasion in the tumor microenvironment (TME). Long-term clinical benefit has been observed in patients receiving PD-(L)1 inhibitors, alone and in combination with other treatments, across multiple tumor types. PD-L1 expression has been associated with response to immune checkpoint inhibitors, and treatment strategies are often guided by immunohistochemistry-based diagnostic tests assessing expression of PD-L1. However, challenges related to the implementation, interpretation, and clinical utility of PD-L1 diagnostic tests have led to an increasing number of preclinical and clinical studies exploring interrogation of the TME by real-time imaging of PD-(L)1 expression by positron emission tomography (PET). PET imaging utilizes radiolabeled molecules to non-invasively assess PD-(L)1 expression spatially and temporally. Several PD-(L)1 PET tracers have been tested in preclinical and clinical studies, with clinical trials in progress to assess their use in a number of cancer types. This review will showcase the development of PD-(L)1 PET tracers from preclinical studies through to clinical use, and will explore the opportunities in drug development and possible future clinical implementation.

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Section: Considerations For the Development And Use Of Pd-(l)1 Pet Tracersmentioning

confidence: 99%

Molecular Imaging and the PD-L1 Pathway: From Bench to Clinic

et al. 2021

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“…Optoacoustic (or photoacoustic) imaging is similar in nature to fluorescence-based approaches, but it is better suited for deep tissue imaging. Instead of attaching a fluorophore, this approach relies upon the conjugation of a light absorbing or quenching moiety [26,27] , i.e., the attachment of a molecule with a high molecular extinction co-efficient and low quantum yield. Unlike a strong fluorescent label, whereby absorbed excitation energy is largely emitted as red-shifted light, a strong photoacoustic label predominantly emits absorbed excitation energy as heat.…”

Section: Approaches To Image Antibody Biodistribution In Vivomentioning

confidence: 99%

“…Arguably the most sensitive and quantifiable way to non-invasively track the biodistribution of an ADC candidate molecule throughout the whole body is by PET (positron emission tomography). Full-size antibodies have a relatively long serum half-life in vivo and so conjugation of the positron emitting isotope Zirconium 89 (t 1/2 = 3.3 days) allows follow up biodistribution scans for more than a week after administration [ 28 ] . Unlike optical signals, the gamma rays detected by PET are much less prone to scatter or attenuation from overlying tissue.…”

Section: Advances In Preclinical Imagingmentioning

confidence: 99%

Advances in preclinical evaluation of experimental antibody-drug conjugates

Lyons¹,

Plenker²,

Trotman³

2021

CDR

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The ability to chemically modify monoclonal antibodies with the attachment of specific functional groups has opened up an enormous range of possibilities for the targeted treatment and diagnosis of cancer in the clinic. As the number of such antibody-based drug candidates has increased, so too has the need for more stringent and robust preclinical evaluation of their in vivo performance to maximize the likelihood that time, research effort, and money are only spent developing the most effective and promising candidate molecules for translation to the clinic. Concurrent with the development of antibody-drug conjugate (ADC) technology, several recent advances in preclinical research stand to greatly increase the experimental rigor by which promising candidate molecules can be evaluated. These include advances in preclinical tumor modeling with the development of patient-derived tumor organoid models that far better recapitulate many aspects of the human disease than conventional subcutaneous xenograft models. Such models are amenable to genetic manipulation, which will greatly improve our understanding of the relationship between ADC and antigen and stringently evaluate mechanisms of therapeutic response. Finally, tumor development is often not visible in these in vivo models. We discuss how the application of several preclinical molecular imaging techniques will greatly enhance the quality of experimental data, enabling quantitative pre-and post-treatment tumor measurements or the precise assessment of ADCs as effective diagnostics. In our opinion, when taken together, these advances in preclinical cancer research will greatly improve the identification of effective candidate ADC molecules with the best chance of clinical translation and cancer patient benefit.

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“…The application of radiolabeled mAbs as imaging probes for both diagnosis and antibody-based treatment planning has always been a vibrant area in molecular imaging and has generated great interest in PET-labeling strategies [33,50]. To date, immuno-PET represents by far the widest field of application of 89 Zr-PET imaging, but in recent years, a growing number of studies has focused on 89 Zr-labeled nanoparticles (NPs) with promising results in tumor detection, drug monitoring, inflammation imaging, as well as tumor-associated macrophage and sentinel lymph mapping [70]. The substantial preclinical data flourished on 89 Zr-PET imaging have led to a successful translation to clinical trials.…”

Section: Introductionmentioning

confidence: 99%

89Zr-PET imaging in humans: a systematic review

Feo

Pontico

Frantellizzi

et al. 2021

Clin Transl Imaging

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Purpose The remarkable amount of preclinical data achieved on 89Zr-PET imaging led to a significant clinical translation, concerning mainly immuno-PET applications. The aim of this systematic review is to provide a complete overview on clinical applications of 89Zr-PET imaging, using a systematic approach to identify and collect published studies performed in humans, sorted by field of application and specific disease subsections. Methods A systematic literature search of articles suiting the inclusion criteria was conducted on Pubmed, Scopus, Central, and Web Of Science databases, including papers published from January 1967 to November 2020. Eligible studies had to be performed on humans through PET imaging with 89Zr-labeled compounds. The methodological quality was assessed through the Quality Assessment of Diagnostic accuracy Studies-2 tool. Results A total of 821 articles were screened. 74 studies performed on humans were assessed for eligibility with the exclusion of further 18, thus 56 articles were ultimately selected for the qualitative analysis. Conclusions 89Zr has shown to be a powerful PET-imaging tool, in particular for radiolabeling antibodies in order to study antigen expression, biodistribution, anticancer treatment planning and follow-up. Other than oncologic applications, 89Zr-radiolabeled antibodies have been proposed for use in inflammatory and autoimmune disorders with interesting results. 89Zr-labeled nanoparticles represent groundbreaking radiopharmaceuticals with potential huge fields of application. To evaluate the clinical usefulness of 89Zr PET-imaging in different conditions and in real-world settings, and to widen its use in clinical practice, further translation of preclinical to clinical data is needed.

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Current Perspectives on 89Zr-PET Imaging

Cited by 90 publications

References 115 publications

Molecular Imaging and the PD-L1 Pathway: From Bench to Clinic

Molecular Imaging and the PD-L1 Pathway: From Bench to Clinic

Advances in preclinical evaluation of experimental antibody-drug conjugates

89Zr-PET imaging in humans: a systematic review

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