Positron Emission Tomography: Applications In Drug Discovery and Drug Development

More than 50 monoclonal antibodies (mAbs), including several antibody–drug conjugates, are in advanced clinical development, forming an important part of the many molecularly targeted anticancer therapeutics currently in development. Drug development is a relatively slow and expensive process, limiting the number of drugs that can be brought into late-stage trials. Development decisions could benefit from quantitative biomarkers, enabling visualization of the tissue distribution of (potentially modified) therapeutic mAbs to confirm effective whole-body target expression, engagement, and modulation and to evaluate heterogeneity across lesions and patients. Such biomarkers may be realized with positron emission tomography imaging of radioactively labeled antibodies, a process called immunoPET. This approach could potentially increase the power and value of early trials by improving patient selection, optimizing dose and schedule, and rationalizing observed drug responses. In this review, we summarize the available literature and the status of clinical trials regarding the potential of immunoPET during early anticancer drug development.

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Utility of positron emission tomography for drug development for heart failure

American Heart Journal ◽

10.1016/j.ahj.2016.02.016 ◽

2016 ◽

Vol 175 ◽

pp. 142-152 ◽

Cited By ~ 6

Author(s):

Lampros Papadimitriou ◽

Peter M. Smith-Jones ◽

Chaudhry M.S. Sarwar ◽

Catherine N. Marti ◽

Kavitha Yaddanapudi ◽

...

Keyword(s):

Heart Failure ◽

Positron Emission Tomography ◽

Drug Development ◽

Emission Tomography ◽

Positron Emission

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Fundamentals of Positron Emission Tomography and Applications in Preclinical Drug Development

The Journal of Clinical Pharmacology ◽

10.1177/00912700122010357 ◽

2001 ◽

Vol 41 (5) ◽

pp. 482-491 ◽

Cited By ~ 84

Author(s):

Simon R. Cherry

Keyword(s):

Positron Emission Tomography ◽

Drug Development ◽

Emission Tomography ◽

Positron Emission ◽

Preclinical Drug Development

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Development of [18F]ICMT-11 for Imaging Caspase-3/7 Activity during Therapy-Induced Apoptosis

Cancers ◽

10.3390/cancers12082191 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2191

Author(s):

Segundo Francisco García-Argüello ◽

Beatriz Lopez-Lorenzo ◽

Bart Cornelissen ◽

Graham Smith

Keyword(s):

Positron Emission Tomography ◽

Drug Discovery ◽

Patient Management ◽

Development Process ◽

Caspase 3 ◽

Emission Tomography ◽

Structural Proteins ◽

Positron Emission ◽

Induced Apoptosis

Insufficient apoptosis is a recognised hallmark of cancer. A strategy to quantitatively measure apoptosis in vivo would be of immense value in both drug discovery and routine patient management. The first irreversible step in the apoptosis cascade is activation of the “executioner” caspase-3 enzyme to commence cleavage of key structural proteins. One strategy to measure caspase-3 activity is Positron Emission Tomography using isatin-5-sulfonamide radiotracers. One such radiotracer is [18F]ICMT-11, which has progressed to clinical application. This review summarises the design and development process for [18F]ICMT-11, suggesting potential avenues for further innovation.

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