Protoporphyrin IX

About: Protoporphyrin IX is a research topic. Over the lifetime, 2250 publications have been published within this topic receiving 65544 citations. The topic is also known as: PpIX.

Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity

Abstract: 5-Aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PpIX), which can be used as a photosensitizer in photodynamic therapy (PDT). Accumulation of PpIX in benign meningioma cells has been observed previously, its exploitation for PDT, however, was discouraged by inconsistent results. To evaluate PDT for benign meningiomas, we investigated PpIX synthesis in two human meningioma cell lines (HBL-52 and BEN-MEN-1), their respective extracellular loss of PpIX and corresponding ferrochelatase (FECH) activity as well as their susceptibility to PDT. We demonstrated PpIX production after 5-ALA administration and minor loss to the extracellular space in both cell lines. However, significantly more (up to five times) PpIX was accumulated in BEN-MEN-1 as compared with HBL-52 cells. FECH activity was 2.7-fold higher in HBL-52 compared with BEN-MEN-1 cells and accordingly higher FECH levels could be shown in HBL-52 cells by Western blot analysis. BEN-MEN-1 cells were much more sensitive to PDT and cells could be almost completely killed by irradiation doses of 2 J cm(-2) , whereas HBL-52 showed only an insufficient response at this irradiation dose. We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA-induced PDT.

δ-Aminolevulinic acid transport in murine mammary adenocarcinoma cells is mediated by beta transporters

Abstract: δ-aminolevulinic acid, the precursor of porphyrin biosynthesis has been used to induce the endogenous synthesis of the photosensitiser protoporphyrin IX for photodynamic therapy in the treatment of various tumours. The aim of this work was to characterise the δ-aminolevulinic acid transport system in the murine mammary adenocarcinoma cell line LM3 using 14C-δ-aminolevulinic acid, to finally improve δ-aminolevulinic acid incorporation in mammalian cells. Our results showed that δ-aminolevulinic acid is incorporated into these cells by two different mechanisms, passive diffusion which is important at the beginning of the incubation, and active transport. Specificity assays suggested that the transporter involved in δ-aminolevulinic acid incorporation is a BETA transporter, probably GAT-2. British Journal of Cancer (2002) 87, 471–474. doi:10.1038/sj.bjc.6600481 www.bjcancer.com © 2002 Cancer Research UK

Two-Dimensional Fully Conjugated Polymeric Photosensitizers for Advanced Photodynamic Therapy

Abstract: Photodynamic therapy (PDT) is attractive for treatment of various cancers, with a high selectivity, minimal long-term effect, and excellent cosmetic appeal. Well water-dispersive photosensitizers with strong optical absorption within the tissue transparency window (700–1000 nm) are needed for efficient PDT. However, clinically used PDT agents based on oligomeric porphyrin units (e.g., protoporphyrin IX) are effective at 532 nm irradiation only. Herein, we synthesized a two-dimensional covalent organic polymer (COP) containing fully conjugated multiple porphyrin macrocycles with sulfonic acid side groups. The resultant COP-P-SO3H is well water-dispersive, showing strong optical absorption within the desired therapeutic window and a high quantum yield of reactive oxygen species, especially singlet oxygen (1O2), for efficiently killing tumor cells upon near-infrared light irradiation. Our first-principles calculations revealed that the observed high yield 1O2 resulted from the unique side-on parallel diatomi...

Laparoscopic fluorescence diagnosis for intraabdominal fluorescence targeting of peritoneal carcinosis experimental studies.

Abstract: Accurate staging is essential to plan therapeutic strategies and appropriate surgical treatment in patients with advanced gastrointestinal malignancies Tremendous efforts have been undertaken to develop more sensitive techniques for the detection of premalignant, early-stage lesions and micrometastases Despite the improvements in preoperative radiologic imaging, precise assessment of the local, regional, or distant extent of the primary tumor can be a major problem Even with computed tomography, magnetic resonance tomography, or ultrasound, minimal tumor spread remains undetected 1 Laparoscopy has emerged as a highly sensitive and specific method of comprehensive abdominal exploration, 2–4 but even with this staging tool an unknown amount of lesions still remain occult Fluorescence diagnosis, also known as photodynamic diagnosis, is being increasingly used to distinguish healthy from diseased tissue in various medical disciplines Especially in urology, fluorescence diagnosis has been used to visualize even small, plane tumors of the bladder The principle of fluorescence diagnosis is based on the accumulation of administered agents, called photosensitizers, in malignant cells After intravenous, oral, or topical application, the agent concentrates in tumors and remains inactive until exposed to light of a specific wavelength When light is delivered to the cancer site, either directly or indirectly through a fiberoptic device, it causes fluorescence of the photosensitizers Whereas earlier generations of photosensitizers, such as Photofrin, were fluorescent at the time of application (exogenous photosensitizers), the photosensitizer aminolevulinic acid (ALA) requires endogenous metabolism before it becomes fluorescent (endogenous photosensitizer) ALA is the natural precursor of the heme pathway Administration of ALA, either systemically or locally, overloads the last step in the heme biosynthesis pathway of tumor cells because of missing negative feedback mechanisms and reduced enzymatic activities This results in increased accumulation of ALA’s metabolite protoporphyrin IX Protoporphyrin IX is a fluorescent agent when stimulated by a defined wavelength within its absorption spectrum One main emission wavelength is within the visible light spectrum at 635 nm (red light) 5 (Fig 1) The positive, red fluorescence of protoporphyrin IX is even detectable in macroscopically invisible tumor foci and can indicate lesions that would have been missed under conventional white-light illumination Detection of fluorescence may be achieved by two distinct technical principles In an imaging system, a two-dimensional picture of the fluorescence intensity distribution of the examined tissue is captured with a charge-coupled device (CCD) camera and displayed on a monitor In a point system, the fluorescence signal is measured in a restricted area and spectrometrically evaluated with an optical multichannel analyzer Figure 1 Typical protoporphyrin IX fluorescence emission spectra of tumor tissue (CC531 colon carcinoma) and surrounding healthy tissue (peritoneal muscle) with its typical peak at 635 nm and a lower secondary emission peak in the far red around 700 Fluorescence diagnosis for surgical staging laparoscopy was adopted to achieve better assessment of disseminated intraabdominal tumor spread 6 This allowed early detection of dysplastic and malignant peritoneal changes caused by metastatic growth of gastrointestinal tumors The feasibility of this modality in the detection of lesions occult to conventional white-light laparoscopy has been evaluated and confirmed as practicable in an experimental setting The use of fluorescence laparoscopy increased the visualization of tumors by 175% compared with white-light laparoscopy 6 In the pilot study, photosensitization parameters, such as an ALA concentration of 30% and a photosensitization time of 4 hours, were chosen according to data gained in urology The following experimental study evaluated the variation of these two parameters to achieve optimal diagnostic results in the detection of peritoneal tumors Both fluorescence detection techniques, the imaging and point system, were applied Serum samples were investigated for ALA and protoporphyrin IX

Quantification of PpIX concentration in basal cell carcinoma and squamous cell carcinoma models using spatial frequency domain imaging

Abstract: 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is an attractive treatment option for nonmelanoma skin tumors, especially for multiple lesions and large areas. The efficacy of ALA-PDT is highly dependent on the photosensitizer (PS) concentration present in the tumor. Thus it is desirable to quantify PS concentration and distribution, preferably noninvasively to determine potential outcome. Here we quantified protoporphyrin IX (PpIX) distribution induced by topical and intra-tumoral (it) administration of the prodrug ALA in basal and squamous cell carcinoma murine models by using spatial frequency domain imaging (SFDI). The in vivo measurements were validated by analysis of the ex vivo extraction of PpIX. The study demonstrates the feasibility of non-invasive quantification of PpIX distributions in skin tumors.