Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

Abstract

This review deals with the development of peptide-based radiopharmaceuticals for the use with positron emission tomography and peptide receptor radiotherapy. It discusses the pros and cons of this class of radiopharmaceuticals as well as the different labelling strategies, and summarises approaches to optimise metabolic stability. Additionally, it presents different target structures and addresses corresponding tracers, which are already used in clinical routine or are being investigated in clinical trials.

Keywords: labelling strategies; metabolic stability; oncology; peptide receptor radiotherapy; positron emission tomography; radiolabelled peptides.

Figure 1

[⁶⁸Ga]Ga-OPS202 PET/CT [antagonist—(A,B)] and [⁶⁸Ga]Ga-DOTATOC PET/CT [agonist—(C,D)] images of a patient with ileal neuroendocrine tumours , showing bilobar liver metastases (dashed lines indicate level of transaxial slices). Studies were performed on the same scanner within 2 months and show same gray (maximal-intensity projections, (A,C) and colour scale (transaxial fusion images, (B,D). Importantly, background activity was lower in liver, intestine, and thyroid with [⁶⁸Ga]Ga-OPS202 than with [⁶⁸Ga]Ga-DOTATOC allowing better identification of the lesions in the liver which are confirmed by subsequent MRI. (Adapted from Nicolas et al., originally puplished in J Nucl Med [142]).

Figure 2

(A) Structure of Glu-C(O)-Lys(Ahx-HBED-CC) (PSMA-11) for labelling with gallium-68 and PSMA-617 for labelling with, e.g., gallium-68 and lutetium-177. (B) ⁶⁸Ga-PSMA-11 PET at baseline and (C) after 2 cycles of [¹⁷⁷Lu]Lu-PSMA-617 therapy demonstrating considerable reduction of PSMA-expressing metastases in lymph nodes and bone (adapted from Fendler et al., originally published in J Nucl Med [183]).

Figure 3

PET images of some clinically studied RGD-based tracers 1 h after intravenous administration in healthy volunteers (B–D,F), a patient with melanoma (A), scrofula (E), lung cancer (G), and hepatocellular carcinoma (H). All images are coronal views. High tracer retention is notable in urogenital tract, due to predominant renal clearance. Intermediate uptake is found in the liver, spleen, and intestines. Reproduced with the permission from [5,45,47,190,207,208,209,210].

Figure 4

Structure of [⁶⁸Ga]Ga-Pentixafor and PET MIP of a patient with multiple myeloma (modified from Wester et al., originally published in Theranostics [226]).