Gliomas: Motexafin Gadolinium-enhanced Molecular MR Imaging and Optical Imaging for Potential Intraoperative Delineation of Tumor Margins.

PURPOSE To investigate the possibility of using motexafin gadolinium (MGd)-enhanced molecular magnetic resonance (MR) imaging and optical imaging to identify the true margins of gliomas. MATERIALS AND METHODS The animal protocol was approved by the institutional animal care and use committee. Thirty-six Sprague-Dawley rats with gliomas were randomized into six groups of six rats. Five groups were euthanized 15, 30, 60, 120, and 240 minutes after intravenous administration of 6 mg/kg of MGd, while one group received only saline solution as a control group. After craniotomy, optical imaging and T1-weighted MR imaging were performed to identify the tumor margins. One-way analysis of variance was used to compare optical photon intensity and MR imaging signal-to-noise ratios. Histologic analysis was performed to confirm the intracellular uptake of MGd by tumor cells and to correlate the tumor margins delineated on both optical and MR images. RESULTS Both optical imaging and T1-weighted MR imaging showed tumor margins. The highest optical photon intensity (2.6 × 10(8) photons per second per mm(2) ± 2.3 × 10(7); analysis of variance, P < .001) and MR signal-to-noise ratio (77.61 ± 2.52; analysis of variance, P = .006) were reached at 15-30 minutes after administration of MGd, with continued tumor visibility at 2-4 hours. Examination with confocal microscopy allowed confirmation that the fluorescence of optical images and MR imaging T1 enhancement exclusively originated from MGd that accumulated in the cytoplasm of tumor cells. CONCLUSION MGd-enhanced optical and MR imaging can allow determination of glioma tumor margins at the optimal time of 15-120 minutes after administration of MGd. Clinical application of these results may allow complete removal of gliomas in a hybrid surgical setting in which intraoperative optical and MR imaging are available.

[1]  B. Qiu,et al.  3.0-T MR imaging of intracoronary local delivery of motexafin gadolinium into coronary artery walls. , 2013, Radiology.

[2]  D. Barone,et al.  Image guided surgery for the resection of brain tumours. , 2014, The Cochrane database of systematic reviews.

[3]  M. Mehta,et al.  Motexafin gadolinium in the treatment of brain metastases , 2007, Expert opinion on pharmacotherapy.

[4]  Rosalind L. Jeffree,et al.  Aminolevulinic acid (ALA)–protoporphyrin IX fluorescence guided tumour resection. Part 1: Clinical, radiological and pathological studies , 2012, Journal of Clinical Neuroscience.

[5]  Jianwen Luo,et al.  In vivo tomographic imaging with fluorescence and MRI using tumor-targeted dual-labeled nanoparticles , 2013, International journal of nanomedicine.

[6]  Jihong Sun,et al.  Development of an intrabiliary MR imaging-monitored local agent delivery technique: a feasibility study in pigs. , 2012, Radiology.

[7]  W. Curran,et al.  Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  Pieter L Kubben,et al.  Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. , 2011, The Lancet. Oncology.

[9]  Guixiang Zhang,et al.  MRI-Monitored Intra-Shunt Local Agent Delivery of Motexafin Gadolinium: Towards Improving Long-Term Patency of TIPS , 2013, PloS one.

[10]  Jeffry R. Alger,et al.  MRI measurement of the uptake and retention of motexafin gadolinium in glioblastoma multiforme and uninvolved normal human brain , 2006, Journal of Neuro-Oncology.

[11]  Erwin G. Van Meir,et al.  Exciting New Advances in Neuro‐Oncology: The Avenue to a Cure for Malignant Glioma , 2010, CA: a cancer journal for clinicians.

[12]  H. Thaler,et al.  Effects of Motexafin gadolinium on tumor metabolism and radiation sensitivity. , 2001, International journal of radiation oncology, biology, physics.

[13]  O. Ganslandt,et al.  Improving the Extent of Malignant Glioma Resection by Dual Intraoperative Visualization Approach , 2012, PloS one.

[14]  C R Wirtz,et al.  Monocrystalline iron oxide nanoparticles: possible solution to the problem of surgically induced intracranial contrast enhancement in intraoperative MR imaging. , 2001, AJNR. American journal of neuroradiology.

[15]  Roberto Rey-Dios,et al.  Intraoperative fluorescence-guided resection of high-grade gliomas: a comparison of the present techniques and evolution of future strategies. , 2014, World neurosurgery.

[16]  M. Matsumae,et al.  Impact of the combination of 5-aminolevulinic acid-induced fluorescence with intraoperative magnetic resonance imaging-guided surgery for glioma. , 2011, World neurosurgery.

[17]  B. Bistrian Case 20-2008: Abdominal pain and weakness after gastric bypass surgery. , 2008, The New England journal of medicine.

[18]  Edoardo Charbon,et al.  Hybrid Small Animal Imaging System Combining Magnetic Resonance Imaging With Fluorescence Tomography Using Single Photon Avalanche Diode Detectors , 2011, IEEE Transactions on Medical Imaging.

[19]  Zhengyang Zhou,et al.  A dual-modal magnetic nanoparticle probe for preoperative and intraoperative mapping of sentinel lymph nodes by magnetic resonance and near infrared fluorescence imaging , 2013, Journal of biomaterials applications.

[20]  E. Atalar,et al.  High‐resolution MRI of deep‐seated atherosclerotic arteries using motexafin gadolinium , 2008, Journal of magnetic resonance imaging : JMRI.

[21]  Volker Seifert,et al.  Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. , 2011, The Lancet. Oncology.

[22]  S. R. Shepard,et al.  Improved Delineation of Glioma Margins and Regions of Infiltration with the Use of Diffusion Tensor Imaging: An Image-Guided Biopsy Study , 2008 .

[23]  A. Moiyadi,et al.  Navigable Intraoperative Ultrasound and Fluorescence-Guided Resections Are Complementary in Resection Control of Malignant Gliomas: One Size Does Not Fit All , 2014, Journal of Neurological Surgery—Part A.

[24]  J A Koutcher,et al.  In vivo animal studies with gadolinium (III) texaphyrin as a radiation enhancer. , 1999, International journal of radiation oncology, biology, physics.

[25]  T. Zhou,et al.  Motexafin-gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a children's oncology group phase 2 study. , 2013, International journal of radiation oncology, biology, physics.

[26]  S. Torp,et al.  Did Survival Improve after the Implementation of Intraoperative Neuronavigation and 3D Ultrasound in Glioblastoma Surgery? A Retrospective Analysis of 192 Primary Operations , 2012, Journal of Neurological Surgery—Part A.

[27]  F. Zanella,et al.  Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. , 2006, The Lancet. Oncology.

[28]  Christopher Nimsky,et al.  Intraoperative MRI in glioma surgery: proof of benefit? , 2011, The Lancet. Oncology.

[29]  Jinzuo Ye,et al.  Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology , 2014, Theranostics.

[30]  M. A. Meyer Malignant gliomas in adults. , 2008, The New England journal of medicine.

[31]  H. Hirschberg,et al.  Evaluation of Motexafin Gadolinium (MGd) as a Contrast Agent for Intraoperative MRI , 2007, Minimally invasive neurosurgery : MIN.