Porphyrins as ligands for 64copper: background and trends

Abstract

Porphyrins and ⁶⁴Cu have emerged as a novel synergic option for applications in PET molecular imaging. Both the characteristics and photophysical properties of macrocyclic porphyrins and the relatively long half-life of the copper isotope, in addition to the increased tumor-specific uptake of porphyrins compared to normal cells, make this complex an attractive option not only for diagnosis but also for therapeutic applications. Herein, we present an overview of the latest results on the development of PET agents based on porphyrins and ⁶⁴Cu, including methods used to improve the selectivity of these macrocycles when conjugated with biological units such as monoclonal antibodies, peptides or proteins.

Fig. 1. Singlet oxygen diagram generation. Figure adapted from ref. 19.

Fig. 2. 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a, brand name Photochlor.

Fig. 3. TACH derivatives.

Fig. 4. Casiopeina and thiosemicarbazone derivatives.

Fig. 5. Proteasome inhibitors.

Fig. 6. Most known bifunctional chelates and their derivatives, adapted from ref. 48.

Fig. 7. Porphyrins structures studied earlier with PET.

Fig. 8. Conjugate based on porphyrin–monoclonal antibody.

Fig. 9. [⁶⁴Cu] PPIX-PEG6-BBN.

Fig. 10. Porphyrin–folate conjugate.

Edgar Aguilar-Ortíz

Amir R. Jalilian

Miguel A. Ávila-Rodríguez