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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.


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Journal ArticleDOI
TL;DR: Observations of an associated response of PBGD and PPIX imply that PBGD may be a rate-limiting determinant for the efficacy of delta-ALA-induced photosensitization when used in photodynamic therapy.
Abstract: As an initial approach to optimize delta-aminolaevulinic acid (delta-ALA)-induced photosensitization of tumours, we examined the response of three enzymes of the haem biosynthetic pathway: delta-ALA dehydratase, porphobilinogen deaminase (PBGD) and ferrochelatase. Only PBGD activity displayed a time- and dose-related increase in tumours after intravenous administration of 300 mg kg(-1) delta-ALA. The time course for porphyrin fluorescence changes, reflecting increased production of the penultimate porphyrin, protoporphyrin IX (PPIX), showed a similar pattern to PBGD. This apparent correlation between PBGD activity and porphyrin fluorescence was also observed in four cultured tumour cell lines exposed to 0.1-2.0 mM delta-ALA in vitro. The increase in PBGD activity and PPIX fluorescence was prevented by the protein synthesis inhibitor cycloheximide. As the apparent Km for PBGD was similar before and after delta-ALA, the increase in PBGD activity was attributed to induction of enzyme de novo. These observations of an associated response of PBGD and PPIX imply that PBGD may be a rate-limiting determinant for the efficacy of delta-ALA-induced photosensitization when used in photodynamic therapy.

83 citations

Journal ArticleDOI
TL;DR: Repeated, not single, ALA treatment without illumination may cause deleterious effects to the liver, which are mediated by oxygen radicals and inhibited by an antioxidant.

82 citations

Journal ArticleDOI
TL;DR: The results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis, and acidosis may slightly enhance the efficacy of ALA -induced PDT.
Abstract: Photodynamic therapy (PDT) is a cancer treatment based on the interaction of light and a photosensitizing chemical. The photosensitizer protoporphyrin IX (PpIX) is generated via the haem biosynthetic pathway after administration of aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic and acidotic relative to normal tissue, which may influence PpIX generation and compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA at various oxygen tensions and H+ ion concentrations, and assessed the effects on PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19 mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15, 0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1) respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was enhanced at lower pH values. These results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may slightly enhance the efficacy of ALA-induced PDT.

81 citations

Journal ArticleDOI
TL;DR: This work compared resection completeness and residual tumor, determined by histopathology, after white light resection (WLR) using an operating microscope versus additional fluorescence guided resections (FGR), which is thought to assist neurosurgeons by visualizing those tumor margins that merge imperceptibly into normal brain tissue and, hence, are difficult to identify.
Abstract: Division of Pathology, St. Michael’s Hospital, Toronto, Ontario, Canada M5B 1W8Background and Objectives: Fluorescence image-guided brain tumor resection is thought to assist neuro-surgeons by visualizing those tumor margins that mergeimperceptibly into normal brain tissue and, hence, aredifficult to identify. We compared resection completenessand residual tumor, determined by histopathology, afterwhite light resection (WLR) using an operating microscopeversus additional fluorescence guided resection (FGR).StudyDesign/MaterialsandMethods:Weemployedanintracranial VX2 tumor in a preclinical rabbit model and afluorescence imaging/spectroscopy system, exciting anddetecting the fluorescence of protoporphyrin IX (PpIX)induced endogenously by administering 5-aminolevulinicacid (ALA) at 4 hours before surgery.Results: Using FGR in addition to WLR significantly in-creased resection completeness by a factor 1.4 from 68 38to 98 3.5%, and decreased the amount of residual tumorpost-resection by a factor 16 from 32 38 to 2.0 3.5% ofthe initial tumor volume.Conclusions: Additional FGR increased completeness ofresection and enabled more consistent resections betweencases. Lasers Surg. Med. 35:181–190, 2004. 2004 Wiley-Liss, Inc.Key words: malignant glioma; VX2; 5-aminolevulinicacid; protoporphyrin IX; fluorescence imaging and spectro-scopyINTRODUCTIONThe treatment of patients with high-grade gliomasremainsamajorchallenge.Theprognosisforthesepatientsis poor, with a median survival time after diagnosis andtreatment of less than 1 year [1,2]. It has been suggestedthat the prognosis is linked to the completeness of tumorremoval [3–6]. A recent [7] study of 416 patients withglioblastoma multiforme indicated that resection of 89% ofthe tumor volume is necessary to improve survival, whileresection of 98% or more resulted in a significant survivaladvantage of 4.2 months compared with a resection of lessthan 98%. However, such a high degree of tumor resectionis often limited by the surgeon’s ability to distinguishresidual tumortissue from surrounding braintissue underconventional white light microscope illumination [8].Hence,methodsenablingbetterintraoperativediscrimina-tion of viable tumor borders should be valuable.Fluorescence imaging and spectroscopy using 5-amino-levulinic acid (ALA)-induced protoporphyrin IX (PpIX) is apotential technique to enhance contrast of viable tumorborders.Althoughadministrationoffluorescentmarkerstoenhance contrast of malignant gliomas is not new [9–13],marking tumors with ALA is conceptually different fromearlier investigations, since ALA is not itself fluorescentbut is metabolized into fluorescent PpIX by a number ofmalignant tumors in situ through enzymes of the heme-biosynthesis pathway [14]. ALA-PpIX has been usedwidely,bothforfluorescencediagnosticsandphotodynamictherapy [15]. It may avoid problems that arise when afluorescent marker is administered directly, such as leak-age from the tumor into surrounding normal brain tissue[16]. We have shown previously [17–20] that ALA-inducedPpIXlevelsinnormalbraintissue,especiallywhitematter,are very low. Clinical and preclinical studies suggest thatthe resulting selectivity of ALA-PpIX in certain braintumors [14,17–25] is a result of various factors. The lowpermeability of ALA at the blood–brain barrier (BBB)[17,26] reduces uptake in normal brain, whereas thecompromised BBB in certain brain tumors is thought topermit selective ALA transport. Different activities ofenzymes in the heme pathway have also been observedbetween tumor and normal tissues, which subsequentlyenable selective production of PpIX [27,28].

80 citations

Patent
29 Oct 2003
TL;DR: In this article, a method for detecting and treating rapidly growing exogenous cells, such as Protista, or parasites, that preferentially accumulate a photoactivatable porphyrin in which 5-aminolevulinic acid or precursor thereof is administered to the patient, or contacted to the exogeneous cells, in an amount sufficient to induce synthesis fluorescence and/or photosensitizing concentrations of a protoporphyryrin IX in the exogenous cells, followed by exposure of the exogene cells to light of photoactivating wavelengths.
Abstract: Methods of detecting and treating rapidly growing exogenous cells, such as Protista, or parasites, that preferentially accumulate a photoactivatable porphyrin in which 5-aminolevulinic acid or precursor thereof is administered to the patient, or contacted to the exogenous cells, in an amount sufficient to induce synthesis fluorescence and/or photosensitizing concentrations of a protoporphyrin IX in the exogenous cells, followed by exposure of the exogenous cells to light of photoactivating wavelengths.

80 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202383
2022132
202157
202061
201958
201858