Selective accumulation of [62Zn]-labeled glycoconjugated porphyrins as multi-functional positron emission tomography tracers in cancer cells

Abstract

Positron-emission tomography (PET) can be used to visualize active stage cancer. Fluorine-18 ([(18)F])-labeled 2-([(18)F])2-deoxy-2-fluoroglucose (([(18)F])-FDG), which accumulates in glucose-dependent tissues, is a good cancer-targeting tracer. However, ([(18)F])-FDG is obscured in glucose-dependent normal tissues. In this study, we assessed the cancer-selective accumulation of zinc-labeled glycoconjugated 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (ZnGlc1-4), both in vitro and in vivo. Experiments using both normal and cancer cells confirmed the relationship between cancer cell-selective accumulation and the substitution numbers and orientations of glycoconjugated porphyrins. ZnGlctrans-2 accumulated at greater levels in cancer cells compared with other glycoconjugated porphyrins. PET imaging showed that ZnGlctrans-2 accumulated in tumor.

Visualization of zinc dynamics in intact plants using positron imaging of commercially available 65Zn

“…Thus far, short-lived 62 Zn has been used in developing a cancer screening agent for PET [27]. Although 65 Zn cannot be administered to humans because of its long half-life, it could be applicable to the kinetic analysis of drugs in small experimental animals if close attention is paid to avoid radioactive contamination in laboratories.…”

Synthesis and biological distribution study of a new carbon-11 labeled porphyrin for PET imaging. Photochemical and biological characterization of the non-labeled porphyrin

“…In this way, tetrapyrrolic macrocycles are a class of agents with upmost interest for the development of theranostic probes due to their flexibility to synthetic modulation, low dark toxicity and high biocompatibility [14][15][16][17]. The application of labeled tetrapyrrolic macrocycles as PET probes has already been described in recent literature, namely through radionuclides with long semi-disintegration periods but with lower positron emission decays, such as 64 Cu [18,19], 68 Ga [20,21], and 62 Zn [22]. However, it should be noted that all these processes required the introduction of a foreign atom in the molecules, causing significant changes in the pharmacokinetic and pharmacodynamic characteristics of the radiotracer and even inducing toxicity like the one observed with 68 Ga-labeled compounds [23,24].…”

Synthesis and Characterization of Novel Fluoro‐glycosylated Porphyrins that can be Utilized as Theranostic Agents

“…However, developing porphyrin‐based PDT agents with multifunctional imaging capabilities and improved pharmacokinetic and pharmacodynamic characteristics, such as tumor specificity and solubility, remains a challenge. In this regard, glycoporphyrins have evolved as an interesting class of theranostic agents, as the addition of carbohydrates to the porphyrin scaffold has shown an impact on the biological behavior of these compounds, both in terms of cellular uptake and subcellular localization, as well as specificity towards cancer cells . For instance, it is well known that cancer cells display increased glucose uptake and metabolism, a phenomenon known as the Warburg effect, through the glucose transporter (GLUT) proteins and that other carbohydrate motifs can also be taken up by the cell through these transporters .…”