Cancer is a leading cause of death worldwide, and early detection is crucial for an effective treatment. Among the various imaging techniques, photoacoustic (PA) imaging, specifically, photoacoustic computed tomography (PACT), has emerged as a new and promising modality due to its high contrasting capability, cost-efficiency, safety, and rapid imaging potentials. However, the performance of PA in cancer imaging is highly dependent on the available contrast agent, and the development of an efficient, safe, and consistent PA contrast agent remains a challenge. Water-soluble chlorophyll proteins (WSCPs)-pigment complexes have shown promise as PA contrast agents due to their high absorption in far-red wavelengths, stability, and photosensitizing ability. However, the native pigments for WSC...[ Read more ]

Cancer is a leading cause of death worldwide, and early detection is crucial for an effective treatment. Among the various imaging techniques, photoacoustic (PA) imaging, specifically, photoacoustic computed tomography (PACT), has emerged as a new and promising modality due to its high contrasting capability, cost-efficiency, safety, and rapid imaging potentials. However, the performance of PA in cancer imaging is highly dependent on the available contrast agent, and the development of an efficient, safe, and consistent PA contrast agent remains a challenge. Water-soluble chlorophyll proteins (WSCPs)-pigment complexes have shown promise as PA contrast agents due to their high absorption in far-red wavelengths, stability, and photosensitizing ability. However, the native pigments for WSCPs, chlorophylls a and b, presents reconstitution issues due to their hydrophobicity, and lower photostability and photosensitizing potentials compared with some metal ion-substituted derivatives. This study aims to develop a novel WSCP-based photoacoustic contrast agent by modifying the chlorophyll pigment and investigate its potential for cancer imaging applications.

In this project, two chlorophyll a derivatives were investigated, chlorophyllide a and zinc pheophorbide a. Chlorophyllide a was synthesized through the endogenous enzymatic cleavage of chlorophyll a's hydrophobic phytol tail, while zinc pheophorbide a was synthesized via the metal ion substitution of chlorophyllide a. These pigments were reconstituted with a WSCP recombinant fusion protein, and the spectral properties, photoacoustic signal generating capabilities, and photostabilities of the WSCP-pigment complexes were analysed. The findings indicated that the dephytylated chlorophyll derivatives exhibited a more efficient reconstitution with WSCP in aqueous solutions. Moreover, the zinc metal ion substitution contributed to improved photostability, while preserving the photoacoustic signal generating capability and the far-red peak absorption. Therefore, zinc pheophorbide a has a high potential to be used as an alternative pigment for the development of WSCP-based photoacoustic contrast agents.