PET tracers based on Zirconium-89

Abstract

Positron emission tomography (PET) imaging with radiolabeled monoclonal antibodies has always been a dynamic area in molecular imaging. With decay half-life (3.3 d) well matched to the circulation half-lives of antibodies (usually on the order of days), (89)Zr has been extensively studied over the last decade. This review article will give a brief overview on (89)Zr isotope production, the radiochemistry generally used for (89)Zr-labeling, and the PET tracers that have been developed using (89)Zr. To date, (89)Zr-based PET imaging has been investigated for a wide variety of cancer-related targets, which include human epidermal growth factor receptor 2, epidermal growth factor receptor, prostate-specific membrane antigen, splice variant v6 of CD44, vascular endothelial growth factor, carbonic anhydrase IX, insulin-like growth factor 1 receptor, among others. With well-developed radiochemistry, commercial availability of chelating agents for (89)Zr labeling, increasingly widely available isotope supply, as well as successful proof-of-principle in pilot human studies, it is expected that PET imaging with (89)Zr-based tracers will be a constantly evolving and highly vibrant field in the near future.

Fig. (1)

Representative radiochemistry for ⁸⁹Zr-labeling. (A) The 6-step route. (B) The 2-step method.

Fig. (2)

PET imaging of HER2 expression in patients with ⁸⁹Zr-trastuzumab. (A) ⁸⁹Zr-trastuzumab PET scans of a patient already on trastuzumab treatment at different time points post-injection revealed an increase over time in the tumor-to-nontumor ratio of tracer uptake. Arrow indicates ⁸⁹Zr-trastuzumab uptake in the only lesion. (B) ⁸⁹Zr-trastuzumab PET of a patient with liver and bone metastases at 5 days post-injection. A number of lesions are indicated by arrows. Adapted from [30].

Fig. (3)

Multimodality imaging of PSMA with ⁸⁹Zr-J591. (A) Cerenkov luminescence imaging of tumor-bearing mice injected with ⁸⁹Zr-J591 in a small animal optical scanner. (B) Corresponding coronal and transverse immunoPET images of the mouse. The signal originates from the LNCaP tumors (PSMA-positive). Mouse bearing two different sized tumors of the same origin was used to demonstrate that differential uptake between the small and large tumors can be discerned by Cerenkov luminescence imaging. Adapted from [43].

Fig. (4)

PET imaging of VEGF expression. (A) Transversal (top) and coronal (bottom) PET images of ⁸⁹Zr-bevacizumab in xenograft mice before (left) and after (right) treatment with a Hsp90 inhibitor. Arrows indicate the tumor. (B) Ki67 staining of the tumor tissue corroborated the PET results. Adapted from [58].