title: Erythrocyte protoporphyrin fluorescence as a biomarker for monitoring antiangiogenic cancer therapy.
abstract: Renal cell carcinoma (RCC) remains one of the greatest challenges of urological oncology and is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and are amenable to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of erythrocyte PpIX fluorescence spectroscopy for monitoring the efficacy of antiangiogenic therapy in metastatic renal cell carcinoma (mRCC), using an orthotopic metastatic mouse model. Balb/C-bearing Renca cells were treated with NIH/3T3-LendSN cells. Lung weight, nodule area, microvascular area (MVA), and erythrocyte PpIX fluorescence were evaluated. Emission spectra were obtained by exciting the samples at 405 nm. There was a significant decrease in lung wet weight, lung nodule area and MVA in the treated group compared to the control group (P < 0.001). Significant differences in autofluorescence shape were observed in the 620-650 nm spectral region. The most intense fluorescence peak was observed at ∼632 nm. The autofluorescence of the control samples was about 53% higher than that of normal blood (P < 0.05). In the group treated with ES, the autofluorescence was about 54% lower than in the control group (P < 0.05). Fluorescence intensity was positively correlated with the nodule area (R (2) = 0.8859; P < 0.001) and MVA (R (2) = 0.9431; P < 0.001) in the ES-treated group. These results demonstrate that the spectroscopic analysis method allows a selective detection of tumor masses. This preliminary study suggests that PpIX fluorescence may be useful as a biomarker for antiangiogenic cancer therapy.
authors.affiliation: Centro de Biotecnologia, IPEN/CNEN-SP, São Paulo, SP, Brazil.
authors.forename: Flávia Gomes
authors.initials: FG
authors.lastname: de Góes Rocha
authors.forename: Karen Cristina Barbosa
authors.initials: KC
authors.lastname: Chaves
authors.forename: Cinthia Zanini
authors.initials: CZ
authors.lastname: Gomes
authors.forename: Camila Barricheli
authors.initials: CB
authors.lastname: Campanharo
authors.forename: Lilia Coronato
authors.initials: LC
authors.lastname: Courrol
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Bellini
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000737:chemistry*; D005453:Fluorescence; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D011524:Protoporphyrins / Q000032:analysis*; D013050:Spectrometry, Fluorescence
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D011524:Protoporphyrins