Deferoxamine Iron Chelation Increases δ‐Aminolevulinic Acid Induced Protoporphyrin IX in Xenograft Glioma Model
Open accessAbstract
Exogenous administration of δ‐aminolevulinic acid (δ‐ALA) leads to selective accumulation of protoporphyrin IX (PpIX) in brain tumors, and has shown promising results in increasing extent of resection in fluorescence‐guided resection (FGR) of brain tumors. However, this approach still suffers from heterogeneous staining and so some tumor margins may go undetected because of this variation in PpIX production. The aim of this study was to test the hypothesis that iron chelation therapy could increase the level of fluorescence in malignant glioma tumors. Mice implanted with xenograft U251‐GFP glioma tumor cells were given a 200 mg kg−1 dose of deferoxamine (DFO), once a day for 3 days prior to δ‐ALA administration. The PpIX fluorescence observed in the tumor regions was 1.9 times the background in animal group without DFO, and 2.9 times the background on average, in the DFO pre‐treated group. A 50% increase in PpIX fluorescence contrast in the DFO group was observed relative to the control group (t‐test P‐value = 0.0020). These results indicate that iron chelation therapy could significantly increase δ‐ALA‐induced PpIX fluorescence in malignant gliomas, pointing to a potential role of iron chelation therapy for more effective FGR of brain tumors.
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DFO significantly enhances ALA-PpIX fluorescence in glioblastoma and skin cancer animal models, although its effect on enhancing ALA-PDT in the skin tumor model is not statistically significant.
“Furthermore, it significantly enhances ALA-PpIX fluorescence in glioblastoma [89] and skin cancer [69] animal models, although its effect on enhancing ALA-PDT in the skin tumor model is not statistically significant.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [89]
DFO has been demonstrated to enhance PpIX fluorescence and/or PDT effects in various studies with different cell lines including skin, bladder, and glioblastoma tumor cells.
“DFO has been demonstrated to enhance PpIX fluorescence and/or PDT effects in various studies with different cell lines including skin, bladder, and glioblastoma tumor cells [86,87,88,89,90].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [89]
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Cites
Berg, K., Anholt, H., Bech, Ø., & Moan, J. (1996) · British Journal of Cancer · doi:10.1038/bjc.1996.423 · Cited by 142 · see citing works
Sinha, A. K., Anand, S., Ortel, B. J., Chang, Y., Mai, Z., Hasan, T., & Maytin, E. V. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603273 · Cited by 114 · see citing works
Choudry, K., Brooke, R. C. C., Farrar, W., & Rhodes, L. E. (2003) · British Journal of Dermatology · doi:10.1046/j.1365-2133.2003.05351.x · Cited by 65 · see citing works
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Research works printed but not linked: 41
- [1]Wen PY Kesari S Malignant gliomas in adults N Engl J Med 2008 359 492 507 18669428
- [2]Stummer W Pichlmeier U Meinel T Wiestler OD Zanella F Reulen HJ A. L.-G. S. Group Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial.[see comment] Lancet Oncology 2006 7 392 401 16648043
- [3]Stummer W Reulen HJ Meinel T Pichlmeier U Schumacher W Tonn JC Rohde V Oppel F Turowski B Woiciechowsky C Franz K Pietsch T Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias Neurosurgery 2008 62 564 576 discussion 564-576 18425006
- [4]Lacroix M Abi-Said D Fourney DR Gokaslan ZL Shi W DeMonte F Lang FF McCutcheon IE Hassenbusch SJ Holland E Hess K Michael C Miller D Sawaya R A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival J Neurosurg 2001 95 190 198 11780887
- [5]Vecht CJ Avezaat CJ van Putten WL Eijkenboom WM Stefanko SZ The influence of the extent of surgery on the neurological function and survival in malignant glioma. A retrospective analysis in 243 patients J Neurol Neurosurg Psychiatry 1990 53 466 471 2166137 PMC1014204
- [6]Hill DL Maurer CR Jr Maciunas RJ Barwise JA Fitzpatrick JM Wang MY Measurement of intraoperative brain surface deformation under a craniotomy Neurosurgery 1998 43 514 526 discussion 527-518 9733307
- [7]Lunn KE Paulsen KD Liu F Kennedy FE Hartov A Roberts DW Data-guided brain deformation modeling: evaluation of a 3-D adjoint inversion method in porcine studies IEEE Trans Biomed Eng 2006 53 1893 1900 17019852
- [8]Ji S Roberts DW Hartov A Paulsen KD Brain-skull contact boundary conditions in an inverse computational deformation model Med Image Anal 2009 13 659 672 19560393 PMC2893576
- [9]Pichlmeier U Bink A Schackert G Stummer W Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients Neuro Oncol 2008 10 1025 1034 18667747 PMC2719000
- [10]Stummer W Novotny A Stepp H Goetz C Bise K Reulen HJ Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients J Neurosurg 2000 93 1003 1013 11117842
- [11]Stummer W Pichlmeier U Meinel T Wiestler OD Zanella F Reulen HJ Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial Lancet Oncol 2006 7 392 401 16648043
- [12]Stummer W Reulen HJ Novotny A Stepp H Tonn JC Fluorescence-guided resections of malignant gliomas--an overview Acta Neurochir Suppl 2003 88 9 12 14531555
- [13]Utsuki S Miyoshi N Oka H Miyajima Y Shimizu S Suzuki S Fujii K Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study Brain Tumor Pathol 2007 24 53 55 18095131
- [14]Utsuki S Oka H Sato S Shimizu S Suzuki S Tanizaki Y Kondo K Miyajima Y Fujii K Histological examination of false positive tissue resection using 5- aminolevulinic acid-induced fluorescence guidance Neurol Med Chir (Tokyo) 2007 47 210 213 discussion 213-214 17527047
- [15]Utsuki S Oka H Sato S Suzuki S Shimizu S Tanaka S Fujii K Possibility of using laser spectroscopy for the intraoperative detection of nonfluorescing brain tumors and the boundaries of brain tumor infiltrates. Technical note J Neurosurg 2006 104 618 620 16619668
- [17]Sato N Moore BW Keevey S Drazba JA Hasan T Maytin EV Vitamin D enhances ALA-induced protoporphyrin IX production and photodynamic cell death in 3-D organotypic cultures of keratinocytes J Invest Dermatol 2007 127 925 934 17068479
- [18]Ortel B Sharlin D O'Donnell D Sinha AK Maytin EV Hasan T Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells Br J Cancer 2002 87 1321 1327 12439724 PMC2408893
- [19]Ortel B Chen N Brissette J Dotto GP Maytin E Hasan T Differentiation-specific increase in ALA-induced protoporphyrin IX accumulation in primary mouse keratinocytes Br J Cancer 1998 77 1744 1751 9667642 PMC2150345
- [21]Curnow A Pye A Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors J Environ Pathol Toxicol Oncol 2007 26 89 103 17725535
- [22]Chang SC MacRobert AJ Porter JB Bown SG The efficacy of an iron chelator (CP94) in increasing cellular protoporphyrin IX following intravesical 5-aminolaevulinic acid administration: an in vivo study J Photochem Photobiol B 1997 38 114 122 9203372
- [23]Collaud S Juzeniene A Moan J Lange N On the selectivity of 5- aminolevulinic acid-induced protoporphyrin IX formation Current Medicinal Chemistry Anti Cancer Agents 2004 4 301 316 15134506
- [24]Friesen SA Hjortland GO Madsen SJ Hirschberg H Engebraten O Nesland JM Peng Q 5-Aminolevulinic acid-based photodynamic detection and therapy of brain tumors (review) International Journal of Oncology 2002 21 577 582 12168102
- [25]Stummer W Stepp H Moller G Ehrhardt A Leonhard M Reulen HJ Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue Acta Neurochir (Wien) 1998 140 995 1000 9856241
- [26]Stummer W Stocker S Wagner S Stepp H Fritsch C Goetz C Goetz AE Kiefmann R Reulen HJ Intraoperative detection of malignant gliomas by 5- aminolevulinic acid-induced porphyrin fluorescence Neurosurgery 1998 42 518 525 discussion 525-516 9526986
- [27]Hefti M von Campe G Moschopulos M Siegner A Looser H Landolt H 5-aminolevulinic acid induced protoporphyrin IX fluorescence in high-grade glioma surgery: a one-year experience at a single institutuion Swiss Med Wkly 2008 138 180 185 18363116
- [28]Toms SA Lin WC Weil RJ Johnson MD Jansen ED Mahadevan-Jansen A Intraoperative optical spectroscopy identifies infiltrating glioma margins with high sensitivity Neurosurgery 2005 57 382 391 discussion 382-391 16234690
- [29]Gibbs SL Chen B O'Hara JA Hoopes PJ Hasan T Pogue BW Protoporphyrin IX level correlates with number of mitochondria, but increase in production correlates with tumor cell size Photochem Photobiol 2006 82 1334 1341 16771607
- [30]Bech O Phillips D Moan J MacRobert AJ A hydroxypyridinone (CP94) enhances protoporphyrin IX formation in 5-aminolaevulinic acid treated cells J Photochem Photobiol B 1997 41 136 144 9440321
- [32]Casas A Batlle AM Butler AR Robertson D Brown EH MacRobert A Riley PA Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures Br J Cancer 1999 80 1525 1532 10408393 PMC2363110
- [33]Ohgari Y Nakayasu Y Kitajima S Sawamoto M Mori H Shimokawa O Matsui H Taketani S Mechanisms involved in delta-aminolevulinic acid (ALA)-induced photosensitivity of tumor cells: relation of ferrochelatase and uptake of ALA to the accumulation of protoporphyrin Biochem Pharmacol 2005 71 42 49 16288996
- [34]Bernhardt PV Coordination chemistry and biology of chelators for the treatment of iron overload disorders Dalton Trans 2007 3214 3220 17893764
- [35]Bring P Partovi N Ford JA Yoshida EM Iron overload disorders: treatment options for patients refractory to or intolerant of phlebotomy Pharmacotherapy 2008 28 331 342 18294113
- [36]Maggio A Light and shadows in the iron chelation treatment of haematological diseases Br J Haematol 2007 138 407 421 17659052
- [37]Hershko C Abrahamov A Konijn AM Breuer W Cabantchik IZ Pootrakul P Link G Objectives and methods of iron chelation therapy Bioinorg Chem Appl 2003 151 168 18365050 PMC2267048
- [38]Aldridge MD Acute iron poisoning: what every pediatric intensive care unit nurse should know Dimens Crit Care Nurs 2007 26 43 48 quiz 49-50 17312404
- [40]Albert FK Forsting M Sartor K Adams HP Kunze S Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis Neurosurgery 1994 34 45 60 discussion 60-41 8121569
- [41]Barker FG 2nd Prados MD Chang SM Gutin PH Lamborn KR Larson DA Malec MK McDermott MW Sneed PK Wara WM Wilson CB Radiation response and survival time in patients with glioblastoma multiforme J Neurosurg 1996 84 442 448 8609556
- [42]Kremer P Mahmoudreza F Ding R Pritsch M Zoubaa S Frei E Intraoperative fluorescence staining of malignant brain tumors using 5- aminofluorescein-labeled albumin Neurosurgery 2009 6 53 60 discussion 60-51 19240573
- [43]Shinoda J Yano H Yoshimura S Okumura A Kaku Y Iwama T Sakai N Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note J Neurosurg 2003 99 597 603 12959452
- [44]Cappellini MD Pattoneri P Oral iron chelators Annu Rev Med 2009 60 25 38 19630568
- [45]Iinuma S Farshi SS Ortel B Hasan T A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin Br J Cancer 1994 70 21 28 8018536 PMC2033301
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Sorted by citations
5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy
Howley, R., Chandratre, S., & Chen, B. (2023) · Bioengineering · doi:10.3390/bioengineering10040496 · Cited by 33 · see citing works
Palasuberniam, P., Kraus, D., Mansi, M., Braun, A., Howley, R., Myers, K. A., & Chen, B. (2019) · Photochemistry and Photobiology · doi:10.1111/php.13091 · Cited by 23 · see citing works
- Authors
- Valdés, P. A., Samkoe, K., O’Hara, J. A., Roberts, D. W., Paulsen, K. D., & Pogue, B. W.
- Affiliations
- Dartmouth College (US)
- Corresponding author
- Pogue, Brian W.
- Venue
- Photochemistry and Photobiology
- Publisher
- Wiley
- Published
- 2010-03
- Volume
- 86
- Issue
- 2
- Pages
- 471-475
- ISSN
- 0031-8655 (ISSN-L)
- 1751-1097
- PMC
- PMC2875336
- OpenAlex
- W2055534257
- Cited by
- 48
- References
- 3
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 3
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Photochemistry and Photobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA120368)
- National Institute of Neurological Disorders and Stroke (R01NS052274)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- deferoxamine, iron chelation therapy, 5-aminolevulinic acid, protoporphyrin IX, fluorescence-guided resection, high-grade glioma, brain tumor imaging, tumor margin detection
- MeSH terms
- Aminolevulinic Acid, Animals, Brain Neoplasms, Deferoxamine, Diagnostic Imaging, Fluorescence, Glioma, Humans, Iron Chelating Agents, Protoporphyrins, Transplantation, Heterologous, Mice
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