Implications of IMT-SPECT for postoperative radiotherapy planning in patients with gliomas

doi:10.1016/S0360-3016(02)02984-X

International Journal of Radiation OncologyBiologyPhysics

Volume 54, Issue 3, 1 November 2002, Pages 842-854

Accepted as an oral presentation at the American Society for Therapeutic Radiology and Oncology Meeting, San Francisco, 2001.

https://doi.org/10.1016/S0360-3016(02)02984-X Get rights and content

Abstract

$Purpose$ : Using MRI, residual tumor cannot be differentiated from nonspecific postoperative changes in patients with brain gliomas after surgical resection. The goal of this study was to analyze the value of ¹²³I-α-methyl-tyrosine-single photon emission CT (IMT-SPECT) in radiotherapy planning of patients with brain gliomas after surgical resection.

$Methods and Materials$ : In 66 patients with surgically resected brain gliomas (33 glioblastomas, 20 anaplastic astrocytomas, 7 anaplastic oligodendrogliomas, and 6 low-grade astrocytomas), IMT-SPECT and MRI were performed for radiotherapy planning. On the MRI/IMT-SPECT fusion images, the volume with IMT uptake was compared with the volume of the hyperintensity areas of T₂-weighted MRI and with the volume of contrast enhancement on T₁-weighted MRI. The regions with IMT uptake and/or MRI changes (composite Vol-MRI/IMT), regions with overlay of IMT uptake and MRI changes (common Vol-MRI/IMT), area with IMT uptake without MRI changes (increase Vol-MRI/IMT), and area with only MRI changes (Vol-MRI minus IMT) were analyzed separately. The planning target volume and boost volume defined using MRI information alone was compared with the planning target volume and boost volume defined by also using the SPECT information.

$Results$ : Focally increased IMT uptake was observed in 25 (38%) of 66 patients, contrast enhancement on MRI was outlined in 59 (89%) of 66 patients, and hyperintensity areas on T₂-weighted MRI were found in all 66 investigated patients. The mean composite Vol-T₂/IMT was 73 cm³. The relative increase Vol-T₂/IMT, mean relative common Vol-T₂/IMT, and mean relative Vol-T₂ minus IMT was 4%, 6%, and 90% of the composite Vol-T₂/IMT, respectively. The mean composite Vol-T₁/IMT was 14 cm³ and the mean relative increase Vol-T₁/IMT, mean relative common Vol-T₁/IMT, and mean relative Vol-T₁ minus IMT was 21%, 4%, and 64% of the mean composite Vol-T₁/IMT, respectively. In 19 (29%) of 66 patients, the focal IMT uptake was located outside the MRI changes. In this subgroup, the mean residual volume defined by focal IMT uptake in MRI/IMT-SPECT images, mean Vol-T₁, and mean Vol-T₂ was 19 cm³, 10 cm³, and 70 cm³, respectively. The mean relative increase T₂/IMT was 14% and T₁/IMT was 61%. In this subgroup, the additional information of SPECT led to an increase in boost volume (mean relative increase BV-IMT) by 20%.

$Conclusion$ : In patients with surgically resected brain gliomas, the size and location of residual IMT uptake differs considerably from the abnormalities found on postoperative MRI. Because of the known high specificity of IMT uptake for tumor tissue, the findings on IMT-SPECT may significantly modify the target volumes for radiotherapy planning. This will help to focus the high irradiation dose on the tumor area and to spare normal brain tissue.

Introduction

Brain gliomas are characterized by a high local recurrence rate after therapy. The first requirement for successful local treatment is an exact definition of the tumor location and extension. Radiotherapy (RT) techniques such as radiosurgery, stereotactic fractionated RT, and intensity-modulated RT allow for a highly precise delivery of the radiation dose to the target volume. One of the most important limitations in the application of these techniques consists in the failure to define the tumor extension precisely. The standard investigations in diagnosis and treatment planning of brain gliomas are MRI and CT 1, 2, 3. Pathologic changes are characterized on MRI and CT by increased water content (edema) and blood-brain barrier (BBB) disruption, visualized as contrast enhancement. Low-grade gliomas show low density or isodensity on CT images and hypointensity or occasionally isointensity on T₁-weighted MRI. They are hyperintense on T₂-weighted images. Peritumoral edema is minimal or absent. A disruption of the BBB is usually absent. High-grade gliomas are hypodense on CT and show low-signal intensity on T₁-weighted MRI and high signal intensity on T₂-weighted MRI. Peritumoral edema is frequently seen. High-grade gliomas usually show contrast enhancement, correlated with the extent of neovascularization and loss of integrity of the BBB owing to tumor infiltration and production of vascular endothelial growth factor. However, both contrast enhancement and hyperintensity areas on T₂-weighted MRI are not always a real measure of tumor extension in low- or high-grade gliomas. Tumor cells have been detected beyond the margins of contrast enhancement in the surrounding edema and even in the adjacent normal-appearing brain tissue. After neurosurgery or RT, BBB disturbances and edema can also be treatment related and cannot be differentiated from persistent tumor on CT or MRI 4, 5, 6. Considering all these problems, it is clearly necessary to search for new methods to define the tumor volume more precisely.

Glioma cells avidly take up radiolabeled amino acids, but only low uptake by normal cerebral tissue is present. Several years ago, histologic studies demonstrated that positron emission tomography (PET) using the radiolabeled amino acid carbon-11 methionine provides a more accurate delineation of intracerebral gliomas than CT and MRI 7, 8, 9. However, because of the short physical half life of carbon-11 (20 min), an on-site cyclotron is required for production of this radiopharmaceutical agent. This has limited the general availability of methionine PET, and so far this technique has not been used for RT planning in clinical practice. ¹²³I-α-methyl-tyrosine (IMT) is a synthetic amino acid whose uptake by gliomas has been shown to closely correlate with the uptake of carbon-11-methionine (10). In contrast to methionine, IMT can be imaged with the much more widely available single photon emission CT (SPECT). It has been demonstrated in several studies that IMT-SPECT allows visualization of gliomas with high contrast 11, 12, 13. Furthermore, IMT-SPECT has been found to be a specific test for the differentiation of tumor recurrence and therapy-induced changes 14, 15.

The aim of the present study was to determine how the findings on IMT-SPECT can influence RT planning after surgical resection of gliomas. In 66 postoperative patients with gliomas who were scheduled to undergo conformal RT, IMT-SPECT images were coregistered with T₁- and T₂-weighted MRI data sets. On these “fusion” images, residual tumor volume was delineated using the combined information of IMT-SPECT and MRI. This tumor volume was compared with the volume of contrast enhancement in T₁-weighted MRI studies and the volume defined by the hyperintensity on T₂-weighted images.

Section snippets

Patients

The study included 66 patients (31 men and 35 women, mean age 50 years, range 18–78) who underwent tumor resection for primary low- and high-grade gliomas, with a mean Karnofsky performance status of 70%. The mean follow-up time, calculated from surgical treatment, was 25 months (range 1–56). Thirty-three patients had glioblastoma, 20 patients anaplastic astrocytoma, 7 patients anaplastic oligodendroglioma, and 6 patients low-grade astrocytoma. CT, MRI, and IMT-SPECT imaging were performed in

Results

The results of the volumetric measurements are summarized in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10 and Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7.

T₂-weighted MRI changes were found in all 66 investigated patients. Fifty-nine patients (89%) had Gd-enhancement areas. In 25 patients (38%), we delineated areas with pathologic IMT uptake in SPECT, and in 19 patients (29%), these changes were located outside the abnormal areas on

Discussion

The goal of this study was to analyze the value of IMT-SPECT in the diagnosis of residual tumor after surgery of brain gliomas and to discuss the consequences for RT planning. The results demonstrate that the tumor volumes defined in fused MRI/IMT-SPECT data sets were significantly different from the abnormalities defined on T₂- and contrast-enhanced T₁-weighted images, suggesting that IMT-SPECT may provide important additional information for RT planning.

MRI is the established imaging modality

Conclusion

In surgically resected patients with brain gliomas, the size and location of residual IMT uptake differs considerably from abnormalities found on postoperative MRI. Because of the known high specificity of IMT uptake for tumor tissue, the findings on IMT-SPECT may significantly modify target volumes for RT planning. This would help to focus the high RT dose on the tumor area and spare normal brain tissue.

MRI is the best tool for describing brain and tumor anatomy, which is of great importance

Acknowledgements

The authors thank U. Pietrzyk from the Max Planck Institute, Cologne-Germany, for generously providing the software for the coregistration of the SPECT and MRI data and L. Sprague for carefully reading the manuscript.

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^☆: Supported by Technical University Munich, Germany—Förderung von Frauen im Rahmen des Dritten Hochschulprogramms.

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Clinical investigation: brainImplications of IMT-SPECT for postoperative radiotherapy planning in patients with gliomas☆

Abstract

Introduction

Section snippets

Patients

Results

Discussion

Conclusion

Acknowledgements

Mayo Clin Proc

Int Radiat Oncol Biol Phys

Int Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int Radiat Oncol Biol Phys

Imaging of gliomas

Semin Oncol

MR imaging of the brain tumors

Eur Radiol

Efficacy of neuroradiological imaging, neurological examination, and symptoms status in follow-up assessment of patients with high-grade gliomas

J Neurosurg

Imaged-based stereotaxic serial biopsies in untreated intracranial glial neoplasm

J Neurosurg

Absence of contrast enhancement on CT brain scans of patients with supratentorial malignant gliomas

Neurology

Positron emission tomography compared with magnetic resonance imaging and computed tomography in supratentorial gliomas using multiple stereotactic biopsies as reference

Acta Radiol

Cerebral gliomaEvaluation with methionine PET

Radiology

Dynamic study of supratentorial gliomas with L-methyl-11C-methionine and positron emission tomography

Am J Neuroradiol

3-(123I)Iodo-alpha-methyltyrosine and (methyl-11C)-L-methionine uptake in cerebral gliomasA comparative study using SPECT and PET

J Nucl Med

Imaging of brain tumors with L-3-(123I)iodo-alpha-methyl tyrosine and SPECT

J Nucl Med

Brain and brain tumor uptake of L-3-(123I)iodo-alpha-methyl-tyrosineCompetition with natural L-amino acids

J Nucl Med

Fluorine-18-FDG PET and iodine-123-IMT SPECT in the evaluation of brain tumors

J Nucl Med

Clinical investigation: brain
Implications of IMT-SPECT for postoperative radiotherapy planning in patients with gliomas☆

Dynamic study of supratentorial gliomas with L-methyl-¹¹C-methionine and positron emission tomography

3-(¹²³I)Iodo-alpha-methyltyrosine and (methyl-¹¹C)-L-methionine uptake in cerebral gliomasA comparative study using SPECT and PET

Imaging of brain tumors with L-3-(¹²³I)iodo-alpha-methyl tyrosine and SPECT

Brain and brain tumor uptake of L-3-(¹²³I)iodo-alpha-methyl-tyrosineCompetition with natural L-amino acids