Intrinsic Fluorescence of Protoporphyrin IX from Blood Samples Can Yield Information on the Growth of Prostate Tumours

Abstract

Prostate cancer is one of the most common types of cancer in men, and unfortunately many prostate tumours remain asymptomatic until they reach advanced stages. Diagnosis is typically performed through Prostate-Specific Antigen (PSA) quantification, Digital Rectal Examination (DRE) and Transrectal Ultrasonography (TU). The antigen (PSA) is secreted by all prostatic epithelial cells and not exclusively by cancerous ones, so its concentration also increases in the presence of other prostatic diseases. DRE and TU are not reliable for early detection, when histological analysis of prostate tissue obtained from a biopsy is necessary. In this context, fluorescence techniques are very important for the diagnosis of cancer. In this paper we explore the potential of using endogenous phorphyrin blood fluorescence as tumour marker for prostate cancer. Substances such as porphyrin derivatives accumulate substantially more in tumours than in normal tissues; thus, measuring blood porphyrin concentration by autofluorescence intensity may provide a good parameter for determining tumour stage. In this study, the autofluorescence of blood porphyrin was analyzed using fluorescence and excitation spectroscopy on healthy male NUDE mice and in those with prostate cancer induced by inoculation of DU145 cells. A significant contrast between the blood of normal and cancer subjects could be established. Blood porphyrin fluorophore showed an enhancement on the fluorescence band around 632 nm following tumour growth. Fluorescence detection has advantages over other light-based investigation methods: high sensitivity, high speed and safety. However it does carry the drawback of low specificity of detection. The extraction of blood porphyrin using acetone can solve this problem, since optical excitation of further molecular species can be excluded, and light scattering from blood samples is negligible.

Early detection of colorectal adenocarcinoma: a clinical decision support tool based on plasma porphyrin accumulation and risk factors

“…Several studies suggest that tumor cells are able to produce porphyrins naturally or after administering their precursor [ 13 , 21 – 23 ] and that porphyrin compounds are responsible for plasma red fluorescence [ 24 , 25 ]. On this basis, we assumed that the difference between the blood fluorescence spectra of colorectal adenocarcinoma patients and control subjects was due to endogenous porphyrins accumulated in cancer cells as a result of a systemic alteration of heme metabolism, and then pumped out to plasma.…”

Using Light for Therapy of Glioblastoma Multiforme (GBM)

“…In their work they chose to activate PpIX by red light (635 nm) delivered from a laser source. The choice of such long wavelength was motivated by the better penetration of red light in the brain tissue but clearly the efficiency of excitation was reduced since the absorption peak of PpIX is 402 nm, which is at the lower limit of visible light, while its peak of emission is 631 nm [52,53] although Mahmoudi et al [47] have also identified a minor peak at 635 nm. In these studies, substantial destruction of tumour tissue was observed in conjunction with signs of vascular damage and necrosis.…”

Porphyrins are increased in the faeces of patients with prostate cancer: a case-control study

“…There are several main hypotheses that seem to explain the alteration in porphyrin metabolism in cancer. One is the hypervascularization typical of malignant neoplasia, which could potentially result in the accumulation of porphyrins due to a greater amount of haemoglobin reacting with the tumour in an attempt to neutralize it [ 5 ]. PpIX also has higher fat solubility in an acidic environment, which is compatible with the presence of lactic acid from anaerobic metabolism found in several tumours [ 4 ].…”

“…A significant difference could be established between PpIX autofluorescence in healthy and prostate cancer animal models. In animals with tumours, PpIX synthesis is altered, which probably interferes with the synthesis of coproporphyrin and other faecal metabolites [ 5 , 6 ]. In this study, we analysed faecal porphyrin levels in subjects with prostate cancer in a case-control study with humans.…”