PET imaging with 89Zr: From radiochemistry to the clinic

Abstract

The advent of antibody-based cancer therapeutics has led to the concomitant rise in the development of companion diagnostics for these therapies, particularly nuclear imaging agents. A number of radioisotopes have been employed for antibody-based PET and SPECT imaging, notably 64Cu, 124I, 111In, and 99mTc; in recent years, however, the field has increasingly focused on 89Zr, a radiometal with near ideal physical and chemical properties for immunoPET imaging. In the review at hand, we seek to provide a comprehensive portrait of the current state of 89Zr radiochemical and imaging research, including work into the production and purification of the isotope, the synthesis of new chelators, the development of new bioconjugation strategies, the creation of novel 89Zr-based agents for preclinical imaging studies, and the translation of 89Zr-labeled radiopharmaceuticals to the clinic. Particular attention will also be dedicated to emerging trends in the field, 89Zr-based imaging applications using vectors other than antibodies, the comparative advantages and limitations of 89Zr-based imaging compared to that with other isotopes, and areas that would benefit from more extensive investigation. At bottom, it is hoped that this review will provide both the experienced investigator and new scientist with a full and critical overview of this exciting and fast-developing field.

Siderophores for molecular imaging applications

“…In contrast to that in the past decade, DFO has established its role in the context of 89 Zr-labelling [80][81][82][83][84]. 89 Zr was proposed as a diagnostic radionuclide for quantitating the biodistribution of radiolabelled antibodies.…”

“…Standardized protocols have been established [90] making 89 Zr labelling for Immuno-PET applications ever more widely applicable. Several reviews have summarized the latest progress of 89 Zr-DFO-conjugated antibodies [82][83][84].…”

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.…”

“…Thus, 89 Zr has a high gamma factor, Γ 15 keV = 6.6 Rcm (weighted average of all gamma rays emitted) [16], meaning that the dose rate for this isotope is significant. The Zr 4+ ion prefers a coordination state of 6 to form a stable complex, and, so far, the most prevalent chelator of 89 Zr is desferrioxamine (DFO) [8,17]. Table 1 summarizes chemical and nuclear decay properties of 89 Zr, including a simplified decay scheme.…”

NEUTRON FLUX MEASUREMENT OF (γ, n)–REACTIONS ON NUCLEI OF ZIRCONIUM

“…Our results may be useful in the study of radiation-resistant materials that can be used in high background radiation. In continuation of these studies, it would be possible to offer a new alternative method for obtaining the isotope 89 Zr, which is very popular in nuclear medicine for use in PET [13].…”