The Photosensitizer Temoporfin (mTHPC) – Chemical, Pre‐clinical and Clinical Developments in the Last Decade^†‡

Abstract

This review follows the research, development and clinical applications of the photosensitizer 5,10,15,20-tetra(mhydroxyphenyl)chlorin (mTHPC, temoporfin) in photodynamic (cancer) therapy (PDT) and other medical applications. Temoporfin is the active substance in the medicinal product Foscanâ authorized in the EU for the palliative treatment of head and neck cancer. Chemistry, biochemistry and pharmacology, as well as clinical and other applications of temoporfin are addressed, including the extensive work that has been done on formulation development including liposomal formulations. The literature has been covered from 2009 to early 2022, thereby connecting it to the previous extensive review on this photosensitizer published in this journal [Senge, M. O. and J. C. Brandt (2011) Photochem. Photobiol. 87, 1240-1296] which followed its way from initial development to approval and clinical application.

Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing

“…Temoporfin (mTHPC, Foscan ® ) [ 6 , 7 , 8 ] is among the most promising photosensitizers used in PDT [ 9 ]. In Europe, since 2001, mTHPC has been approved for the photodynamic treatment of head and neck squamous cell carcinoma (HNSCC) [ 6 ].…”

“…Despite its excellent photophysical properties, the poor solubility of mTHPC still represents a challenge in clinical settings. In physiological environments, mTHPC forms aggregates, resulting in the quenching of its excited states and, consequently, in reduced production of ROS and in very poor stability [ 6 , 7 , 8 ]. The approved formulation of Foscan ® is a solution of mTHPC in a mixture of ethanol and propylene glycol, which, however, can cause severe side effects post-injection [ 10 ].…”

“…Due to the hydrophobic character of mTHPC, numerous studies were aimed to create novel delivery systems based on nanosystems such as polymers, liposomes, and nanoparticles [ 7 , 8 , 11 ] with the intent to increase solubility and stability in a physiological environment (i.e., third-generation photosensitizers) [ 12 ].…”

Antitumor Immunity Mediated by Photodynamic Therapy Using Injectable Chitosan Hydrogels for Intratumoral and Sustained Drug Delivery

“…Owing to the poor water-solubility of m -THPC (Log P oc/w ∼ 9.24), it is employed in clinical applications as a formulation based on a mixture of anhydrous ethanol and propylene glycol. This formulation is marketed under the trade name Foscan . , To avoid precipitation, Foscan administration requires a slow intravenous infusion through an indwelling catheter, which causes patient’s discomfort. The high hydrophobicity of m -THPC impacts its pharmacokinetics and biodistribution.…”

“…This formulation is marketed under the trade name Foscan. 7,8 To avoid precipitation, Foscan administration requires a slow intravenous infusion through an indwelling catheter, which causes patient's discomfort. The high hydrophobicity of m-THPC impacts its pharmacokinetics and biodistribution.…”