Positive Progress in ImmunoPET—Not Just a Coincidence

Abstract

The identification of tumor tissue biomarkers has led to the production, validation, and Food and Drug Administration-approval of a number of antibody-based targeted therapeutics in the past two decades. As a result of the significant role that these immunotherapeutics play in the management of cancer, and the potential utility of complementary imaging agents, immunoPET imaging has generated considerable interest. This update discusses the important factors to consider when designing a PET (positron emission tomography) imaging agent from the molecular target to the biological targeting molecule and radionuclide combination and also reviews recent preclinical and clinical findings in the immunoPET field. Although there are a variety of radionuclides that are currently utilized in PET studies, this update focuses on four of the positron emitters commonly used in labeling proteins: iodine-124, zirconium-89, copper-64, and fluorine-18. Notable advances in the preclinical setting include the continued development of immunoPET probes to predict the biodistribution of related radioimmunotherapeutics, the success of nontraditional radionuclide and antibody fragment combinations, the broader use of zirconium-89, and the recent emergence of 18 F-labeled diabodies for same-day imaging. Antibody-based PET probes constitute a valuable class of molecular imaging agents, and the progress made preclinically should expedite the transition of these targeted diagnostics to clinical applications.

Differential Receptor Tyrosine Kinase PET Imaging for Therapeutic Guidance

“…We developed F(ab9) 2 -based imaging agents specific for the external domains of EGFR and HER3, obtaining probes with improved in vivo properties in comparison to whole monoclonal antibodies (20,21). Our probes bind their target proteins with a dissociation constant of 8.6 nM for EGFR and 6.8 nM for HER3 expressed on the cellular surface (Supplemental Fig.…”

Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

“…These pharmaceutical developments rely crucially on the antibody's ability to localize at sites of disease. Immuno-PET, a molecular imaging technique combining the high resolution and sensitivity of positron emission tomography (PET) and the selective localization of antibodies at their target in vivo, has profited from recent technical advances and the availability of Good Manufacturing Practice (GMP)-grade radionuclides, and might play an important role in the future both in cancer staging and tailoring of therapy (6)(7)(8)(9)(10).…”

“…Although radiometals (e.g., Zr and Cu) are attached via chelators, iodine can be coupled directly with the antibodies without impacting on its pharmacokinetic properties. As iodine might be cleaved from the protein complex upon internalization, the use of 124 I is particularly attractive for noninternalizing antibodies (7,8).…”

Routine Production of 89Zr Using an Automated Module

“…A search of the PubMed database [6] found over 55 publications with 89 Zr mentioned in the title, 75% of which had been published since 2009. In particular, 89 Zr holds significant potential for immunoPET [4,[7][8][9][10], a growing technique that uses radiolabelled antibodies, antibody fragments, and peptides for the in vivo molecular imaging of antigens using PET [7,[11][12][13][14]. 89 Zr is well-suited for this technique because it is a positron-emitter with a half-life (t 1/2 = 3.27 days) that is long enough to accommodate the targeting time for these relatively large imaging agents, which is on the order of days.…”