Analysis of 5-aminolevulinic acid–induced fluorescence in 55 different spinal tumors

Millesi, Matthias; Kiesel, Barbara; Wöehrer, Adelheid; Hainfellner, Johannes A.; Novak, Klaus; Martínez-Moreno, Mauricio; Wolfsberger, Stefan; Knosp, Engelbert; Widhalm, Georg

doi:10.3171/2013.12.focus13485

Cited by 60 publications

(55 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12,15,19,20,39,41,42,47,49,50 Spectroscopic analysis allows positive identification of the typical PpIX fluorescence spectrum with its major peak at 635 nm and a second minor peak at 710 nm, and enables improved detection of diagnostically significant levels of PpIX (i.e., above autofluorescence) in tissues that do not demonstrate visible fluorescence. 12,39,42,49 Spectroscopic probes increase sensitivity primarily by improving the efficiency of light excitation and detection relative to wide-field fluorescence imaging.…”

Section: Discussionmentioning

confidence: 99%

“…However, an important distinction should be drawn between these spectroscopic probe studies and the present work, in that most published reports 12,19,39,41 use the “raw” fluorescence signal to infer the diagnostic performance of the fluorophore. Although these probes may offer more sensitivity to PpIX fluorescence than the visual wide-field imaging that is commercially available through the fluorescence-adapted operating microscope, these probe measurements are semiquantitative 44 and do not account for the variable attenuation caused by tissue optical properties on the detected fluorescence, 3,16,25,28,44,49,50 and therefore, do not calculate the absolute fluorescent biomarker concentrations.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

Valdés

Jacobs

Harris

et al. 2015

JNS

145

137

View full text Add to dashboard Cite

OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively. CONCLUSIONS The authors’ initial experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However, the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs, and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed, at least in the authors’ initial experience reported here, if quantitative detection methods are deployed, the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches the accuracy associated with visual fluorescence in HGGs.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

Valdés

Jacobs

Harris

et al. 2015

JNS

145

137

View full text Add to dashboard Cite

show abstract

“…Cancer-specific navigation has been successfully introduced in glioma surgery with improvement in outcomes,(5–7) but this strategy lacks specificity and applicability to other cancer types. (8) Adapting therapeutic antibodies for intraoperative cancer imaging leverages the known safety profile of the antibody to facilitate the clinical translation of the technique for surgical navigation in oncology. (9, 10)…”

Section: Introductionmentioning

confidence: 99%

Safety and Tumor Specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer

Rosenthal

Warram

Boer

et al. 2015

Clinical Cancer Research

389

388

View full text Add to dashboard Cite

Purpose Positive margins dominate clinical outcomes after surgical resections in most solid cancer types including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that epidermal growth factor receptor (EGFR) can be targeted for safe and specific real-time localization of cancer. Experimental design A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n=12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days post-infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology. Results There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathological analysis of tissues ex-vivo. Fluorescence levels positively correlated with EGFR levels. Conclusion We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology.

show abstract

“…Based on these encouraging data, 5-ALA was also applied in the management of other tumors and was considered useful, particularly for suspected low-grade gliomas, stereotactic brain tumor biopsies, and specific spinal neoplasms. 12,20,37,[39][40][41] Recently, the presence of 5-ALA-induced PpIX fluorescence was also observed in intracranial meningiomas. 1,4,5,7,8,10,11,13,16,18,21,22,35,38,42 However, the benefits of PpIX fluorescence in intracranial meningioma surgery had not been systematically analyzed in a large patient series.…”

mentioning

confidence: 99%

Analysis of the surgical benefits of 5-ALA–induced fluorescence in intracranial meningiomas: experience in 204 meningiomas

Millesi

Kiesel

Mischkulnig³

et al. 2016

JNS

Self Cite

View full text Add to dashboard Cite

OBJECTIVE One of the most important causes for recurrence of intracranial meningiomas is residual tumor tissue that remains despite assumed complete resection. Recently, intraoperative visualization of meningioma tissue by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence was reported. The aim of this study was to investigate the possible surgical benefits of PpIX fluorescence for detection of meningioma tissue. METHODS 5-ALA was administered preoperatively to 190 patients undergoing resection of 204 intracranial meningiomas. The meningiomas' PpIX fluorescence status, fluorescence quality (strong or vague), and intratumoral fluorescence homogeneity were investigated during surgery. Additionally, specific sites, including the dural tail, tumor-infiltrated bone flap, adjacent cortex, and potential satellite lesions, were analyzed for PpIX fluorescence in selected cases. RESULTS PpIX fluorescence was observed in 185 (91%) of 204 meningiomas. In the subgroup of sphenoorbital meningiomas (12 of 204 cases), the dural part showed visible PpIX fluorescence in 9 cases (75%), whereas the bony part did not show any PpIX fluorescence in 10 cases (83%). Of all fluorescing meningiomas, 168 (91%) showed strong PpIX fluorescence. Typically, most meningiomas demonstrated homogeneous fluorescence (75% of cases). No PpIX fluorescence was observed in any of the investigated 89 dural tails. In contrast, satellite lesions could be identified through PpIX fluorescence in 7 cases. Furthermore, tumor-infiltrated bone flaps could be visualized by PpIX fluorescence in all 13 cases. Notably, PpIX fluorescence was also present in the adjacent cortex in 20 (25%) of 80 analyzed cases. CONCLUSIONS The authors' data from this largest patient cohort to date indicate that PpIX fluorescence enables intraoperatively visualization of most intracranial meningiomas and allows identification of residual tumor tissue at specific sites. Thus, intraoperative detection of residual meningioma tissue by PpIX fluorescence might in future reduce the risk of recurrence.

show abstract

Analysis of 5-aminolevulinic acid–induced fluorescence in 55 different spinal tumors

Cited by 60 publications

References 47 publications

Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

Safety and Tumor Specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer

Analysis of the surgical benefits of 5-ALA–induced fluorescence in intracranial meningiomas: experience in 204 meningiomas

Contact Info

Product

Resources

About