Radiolabeling of Nanoparticles and Polymers for PET Imaging

Abstract

Nanomedicine has become an emerging field in imaging and therapy of malignancies. Nanodimensional drug delivery systems have already been used in the clinic, as carriers for sensitive chemotherapeutics or highly toxic substances. In addition, those nanodimensional structures are further able to carry and deliver radionuclides. In the development process, non-invasive imaging by means of positron emission tomography (PET) represents an ideal tool for investigations of pharmacological profiles and to find the optimal nanodimensional architecture of the aimed-at drug delivery system. Furthermore, in a personalized therapy approach, molecular imaging modalities are essential for patient screening/selection and monitoring. Hence, labeling methods for potential drug delivery systems are an indispensable need to provide the radiolabeled analog. In this review, we describe and discuss various approaches and methods for the labeling of potential drug delivery systems using positron emitters.

Figure 1

Illustration of the Enhanced Permeation and Retention (EPR) effect of macromolecular structures as drug delivery systems in malignant tissue.

Figure 2

The Clock-Of-Nuclides showing the positron emitters used for radiolabeling of NPs or polymers, so far. Clockwise starting at ¹³N (at noon) with the shortest physical half-life and ending at ⁷⁴As with the longest physical half-life.

Figure 3

Radiolabeling of thiol-functionalized Au-NPs using a maleimido-[¹⁸F]FDG. [¹⁸F]FDG was produced in accordance with the standard protocol [21].

Figure 4

(A) Pre-targeting/labeling protocol for in vivo click reaction. (B) 3D PET images (upper row) and transversal slides (lower row) of a U87 MG tumor-bearing mouse injected with ω-[¹⁸F]fluoro-pentaethylene glycolic azide without pretargeting. (C) 3D PET images (upper row) and transversal slides (lower row) of a U87 MG tumor-bearing mouse injected with ω-[¹⁸F]fluoro-pentaethylene glycolic azide with pretargeting using DBCO-PEG-NPs. Reprinted with permission from S.B. Lee et al. [22]; Copyright 2013 John Wiley and Sons.

Figure 5

Three general radiolabeling approaches using metallic radionuclides and nanoparticles.

Figure 6

(A–D) PET images of ¹³N-nanoparticles of different size in Sprague-Dawley rats (60 min p.i.). (A) 10 nm, (B) 40 nm, (C) 150 nm, (D) 10 µm. (E) Schematic anatomical overview with localization of important organs. (F) The corresponding particles size distribution of the employed NPs. Reprinted with permission from Pérez-Campaña C. et al. [10]; Copyright 2013 American Chemical Society.

Figure 7

Thiol-functionalization of HPMA-based polymers and radiolabeling strategy for ^72/74As-labeled HPMA-based polymers.