PET imaging with radiolabeled antibodies and tyrosine kinase inhibitors: immuno-PET and TKI-PET

Abstract

During the last decade, the discovery of critical tumor targets has boosted the design of targeted therapeutic agents with monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) receiving most of the attention. Immuno-positron emission tomography (immuno-PET) and TKI-PET, the in vivo tracking and quantification of mAbs and TKIs biodistribution with PET, are exciting novel options for better understanding of the in vivo behavior and efficacy of these targeted drugs in individual patients and for more efficient drug development. Very recently, current good manufacturing practice compliant procedures for labeling of mAbs with positron emitters have been described, as well as the preparation of some radiolabeled TKIs, while the first proof of principle studies has been performed in patients. In this review, technical developments in immuno-PET and TKI-PET are described, and their clinical potential is discussed. An overview is provided for the most appealing preclinical immuno-PET and TKI-PET studies, as well as the first clinical achievements with these emerging technologies.

Fig. 1

Immuno-PET images with ⁸⁹Zr-cmAb U36 of head and neck cancer patient with a tumor on the right side of the soft palate and a lymph node metastasis at the left side of the neck (level III). Images were obtained 72 h post injection. a Coronal image of primary tumor. b Coronal image of lymph node metastasis in the neck. c Sagittal image of primary tumor. d Sagittal image of lymph node metastasis in the neck (from Börjesson et al. [21])

Fig. 2

Examples of ⁸⁹Zr-trastuzumab uptake 5 days p.i. in a patient with liver and bone metastases (a) and two patients with multiple bone metastases (b, c). A number of lesions have been specifically indicated by the arrows (from Dijkers et al. [36])

Fig. 3

¹¹C-erlotinib micro-PET imaging of lung cancer xenografts. Coronal micro-PET images of anesthetized athymic nude mice xenografted with A549 (a), NCI358 (b), and HCC827 (c) lung cancer cells at the left shoulder. A549 and NCI358 cell lines are less sensitive to erlotinib than HCC827, while the latter cell line harbors an inframe deletion mutation in exon 19 of EGFR. White arrows tumors. It can be concluded that the highest tumor uptake of ¹¹C-erlotinib was found in the most sensitive xenograft line HCC827. The hot spot in a (red arrow) was found in all mice; however, it is not possible to show it in all mice as the tumors are located in different planes. Liver is seen with very high activity with spillover to the surrounding area (arrowheads) (derived from Memon et al. [47])