Transforming a Targeted Porphyrin Theranostic Agent into a PET Imaging Probe for Cancer

Abstract

Porphyrin based photosensitizers are useful agents for photodynamic therapy (PDT) and fluorescence imaging of cancer. Porphyrins are also excellent metal chelators forming highly stable metallo-complexes making them efficient delivery vehicles for radioisotopes. Here we investigated the possibility of incorporating 64Cu into a porphyrin-peptide-folate (PPF) probe developed previously as folate receptor (FR) targeted fluorescent/PDT agent, and evaluated the potential of turning the resulting 64Cu-PPF into a positron emission tomography (PET) probe for cancer imaging. Noninvasive PET imaging followed by radioassay evaluated the tumor accumulation, pharmacokinetics and biodistribution of 64Cu-PPF. 64Cu-PPF uptake in FR-positive tumors was visible on small-animal PET images with high tumor-to-muscle ratio (8.88 ± 3.60) observed after 24 h. Competitive blocking studies confirmed the FR-mediated tracer uptake by the tumor. The ease of efficient 64Cu-radiolabeling of PPF while retaining its favorable biodistribution, pharmacokinetics and selective tumor uptake, provides a robust strategy to transform tumor-targeted porphyrin-based photosensitizers into PET imaging probes.

Porphyrin-based photosensitizers and the corresponding multifunctional nanoplatforms for cancer-imaging and phototherapy

“…Zheng et al have also recently synthesized a tumor specific porphyrinpeptide folate (PPF) probe with a 64 Cu label for PET imaging. 64 CuPPF uptake in FRpositive tumors was visible on smallanimal PET images with high tumortomuscle ratio (8.88 ± 3.60) observed after 24 h [98]. PET can be used for monitoring efficacy of PDT.…”

Applications of phototheranostic nanoagents in photodynamic therapy

“…Chlorin e6 in combination with upconverting nanoparticles has been used to image and treat breast cancer and cervical cancer in vivo (entry 9, Table 1) [219,220] (upconversion refers to nonlinear optical processes in which the sequential absorption of photons results in emission of light at a shorter wavelength than the excitation wavelength [221]). Photosensitizers such as bacteriopheophorbide [215], pyropheophorbide-a [164], protoporphyrin IX [26,222], methylene blue [211][212][213], and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin [223] have been used in conjunction with nanoparticles for diagnosis and treatment of various cancers. Use of encapsulated photosensitizers in phototheranostics has been reported.…”

Emerging applications of porphyrins in photomedicine

“…As shown in Figure 3, Shi et al reported 64 Cu porphyrin radiolabeling in a multifunctional chelator complex [59]. This complex served as an optical imaging probe, a PDT agent, and a PET imaging probe.…”