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Differentiating Histologie Malignancy of Primary Brain Tumors: Pentavalent Technetium-99M-DMSA

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Differentiating Histologie Malignancy of Primary Brain Tumors: Pentavalent Technetium-99M-DMSA Differentiating Histologie Malignancy of Primary Brain Tumors: Pentavalent Technetium-99m-DMSA Tsuneo Mirano, Hidenori Otake, Takashi Shibasaki, Masaru Tamura and Keigo Endo Department of Nuclear Medicine and Department of Neurosurgery, Gunma University, School oj Medicine, Gunma, Japan This study assessed pentavalent 99mTc-DMSA uptake in primary tumor appeared to exhibit a prolonged washout phase of radioactivity when compared to the blood pool (16). We brain tumors and evaluated the relationship between retention and thought that there were several factors affecting tumor uptake, histologie malignancy. Methods: SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of but only a prolonged washout phase may be hypothetically approximately 555 MBq 99mTc(V)-DMSA in patients with brain specific to tumor histology and histologie grade. Uptake ratios tumors. Sixty studies were performed in 57 patients and 63 (early and delayed), retention ratio and retention index were lesions were demonstrated: 11 glioblastomas, 13 anaplastia astro- calculated to evaluate and differentiate tumor-specific from cytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and nontumor-specific components. These numerical values were 10 schwannomas. Uptake ratios, retention ratio and retention index compared statistically with tumor histology and histologie were calculated and compared with tumor histology and malignancy grade of the primary brain tumors. grade. Results: Approximately 95% of both benign and malignant primary brain tumors were demonstrated by ""TcfVJ-DMSA SPECT images. False negative was noted in three cases. The early uptake MATERIALS AND METHODS ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor histology or histologie Patients malignancy. The delayed uptake ratio, retention ratio and retention Patients with a brain tumor on x-ray computed tomography index were higher in the malignant tumors than the benign tumors. (X-CT) or MRI were selected for this imaging. A [99nTc](V)- Conclusion: Technetium-99m(V)-DMSA washout from the tumor DMSA SPECT study was performed before surgical resection or was highly dependent upon its histology and histologie malignancy. stereotactic biopsy. Tumor size was measured by surgical speci The delayed uptake ratio considerably reflected tumor histology and men, contrast-enhanced CT and gadolinium-enhanced MR images. differentiated benign tumors from malignant tumors. The retention Tumor vascularity was also evaluated by dynamic SPECT images ratio and retention index significantly reflected tumor histology and ([123I]IMP or 99mTc-HMPAO), contrast-enhanced CT and gadolin histologie grade of primary brain tumors and clearly distinguished ium-enhanced MR image and classified into three groups: hyper- between benign and malignant tumors with statistically significant difference (p < 0.05). These results could suggest the clinical utility vascular, normovascular and hypovascular tumors. of 99mTc(V)-DMSA in imaging primary brain tumors and differenti Final diagnosis was made by histopathology of the specimens ating their histological malignancy grade noninvasively. obtained by surgical procedure or stereotactic biopsy according to Key Words: pentavalent technetium-99m-DMSA; histologiemalig the WHO histological classification: glioblastoma, anaplastic as- nancy; brain tumors; retention index; SPECT trocytoma (astrocytoma Grade 3), astrocytoma (astrocytoma Grade J NucíMed 1997; 38:20-26 2), pilocytic astrocytoma (astrocytoma Grade 1), meningioma and schwannoma. \^T and MRI can demonstrate smaller lesions due to their fine Imaging spatial resolution. Furthermore, their contrast enhancement, Technetium-99m(V)-DMSA was prepared using a commercially which is mainly dependent upon the disrupted blood-brain available dimercaptosuccinic acid (DMSA) kit. Briefly, the barrier, has been used to localize the tumors, but prediction of Techne®DMSA kit (Daiichi Radioisotope, Tokyo, Japan) contains histopathological diagnosis is difficult. One of the most widely 1.4 mg dimercaptosuccinic acid and 0.5 mg SnCl2 •2H20. A used radiopharmaceuticals, [2°'Tc]chloride, has been reported DMSA kit added with 200 ju.17% of sodium bicarbonate solution to differentiate, to some extent, benign lesions from malignant (NaHCO3) was reconstituted with 2 ml of 99rnTc-pertechnetate lesions of the lung (/), thyroid gland (2) and brain tumors (3-7), depending upon the uptake ratio and prolonged washout solution (approximately 740 MBq) (15). phase of radiotracer from the tumor tissue (5-7). SPECT images of the brain were obtained at 30 min and 3 hr Pentavalent 99mTc-dimercaptosuccinic acid (99mTc(V)- after intravenous administration of approximately 555 MBq 99mTc(V)-DMSA, using a ring-type SPECT scanner dedicated for DMSA) was developed as a tumor imaging agent (8-9), and its brain studies (Headtome, Schimadzu Corp., Kyoto, Japan). Image accumulation has been reported in the medullary carcinoma of acquisition was performed for approximately 0.4 to 0.7 X IO6 the thyroid (¡0), soft tissue tumors (11-12), lung cancers (13) and osseous metastatic tumors (13-14). We have established a counts per slice on 64 X 64 matrix with a 20% symmetric window simple and easy method to prepare 99mTc(V)-DMSA from at 140 keV. Butterworth and Ramachandran filters were used to reconstruct images in the transverse plane. Each image was commercially available DMSA kits (75) and have imaged corrected for tissue attenuation with the standard method using primary brain tumors to assess clinical usefulness. [99nTc]pertechnetate in a phantom. In-plane spatial resolution was Watkinson et al. reported that there was no evidence of active uptake of 99mTc(V)-DMSA by squamous cell cancer, and the 9.6 mm (FWHM). Image Analysis Received Oct. 18, 1995; revision accepted June 15, 1996. Technetium-99m(V)-DMSA SPECT images were compared For correspondence or reprints contact: Tsuneo Mirano, MD, Department of Nuclear Medicine, Gunma University, School of Medicine, 3-39-15 Showa-machi, Maebashi, with X-CT and MR images and tumor histology. Accumulation in Gunma 00371, Japan. the brain tumors was evaluated visually on SPECT images, and a 20 THE JOURNALOFNUCLEARMEDICINE•Vol. 38 •No. 1 •January 1997 TABLE 1 Summary of 57 Patients with Primary Brain Tumors Patient Age ratio (Ratio/Index)3.06/91.65.55/1421.87/75.13.67/97.34.50/75.04.64/96.93.04/1004.18/1154.85/98.07.27/1291.79/75.95.00/1465.08/1902.34/48.87.35/1042.48/1191.28/54.91.65/57.90.32/15.33.00/1351.82/63.92.81/73.81.32/64.12.07/70.61.77/44.7(-)/-)0.93/54.11.62/71.10.40/14.50.90/33.10.34/21.10.74/14.22.38/44.80.43/20.4(-)/<-)0.93/43.9(-)/(-)0.42/10.90.61/11.00.84/14.00.42/5.650.18/6.64-0.08/-3.130.21/10.10.03/1.450.35/17.40.57/18.30.56/19.90.39/18.5-0.09/-4.190.76/38.81.33/28.50.18/6.840.15/5.620.47/13.20.05/0.770.36/10.70.06/1.19Uptakeno.(yr)1 (cm)3.8size (Early/Delayed)3.34/6.403.91/9.462.49/4.363.77/7.446.00/10.54.79/9.433.04/6.083.62/7.804.95/9.805.63/12.92.03/5.303.43/8.432.67/7.754.80/7.147.05/14.42.08/4.562.33/3.612.85/4.502.09/2.412.22/5.222.85/4.673.81/6.622.06/3.382.93/5.003.96/5.73(-)/(-)1.72/2.652.28/3.902.76/3.162.72/3.621.61/1.955.21/5.955.31/7.692.11/2.54(-X(-)2.12/3.05(-)/(-)3.86/4.285.55/6.165.98/6.827.44/7.862.71/2.892.56/2.482.08/2.292.07/2.102.01/2.363.11/3.682.82/3.382.11/2.502.20/2.111.96/2.724.67/6.002.63/2.812.67/2.823.57/4.046.51/6.563.35/3.715.05/5.11Retention 452 gangliaRt.basal 6.83.5x 4.3 x 693 lobeLt.temporal 4.73.4X 4.0 x 474 lobeLt.temporal 4.43.2x 3.9 x lobeFrontaltemporal 5.03.9x 4.2 X 725 lobesLt. 4.94.0x 4.2 x 486 lobeRt.frontal 5.62.2x 4.3 x 107 lobeRt.temporal 4.02.8x 3.5 x 638 lobeLt.pariétal 4.63.8x 3.8 x 429 lobeLt.témpora-parietal 4.84.4x 4.6 x 4110 lobeRt.témpora-parietal 5.83.5x 4.5 x 7711 lobeLt.temporal 5.33.7x 4.0 x 6712 3)Astrocytoma(G HippocampusLt. 5.01.3X2.3X4.24.9x 3.8 x 5513 3)Astrocytoma(G régionRt.fronto-parietal 5114 3)Astrocytoma(G lobeRt.temporal 5.93.5x 5.6 x 3515 3)RécurrenceAstrocytoma(G lobeRt.frontal 7.04.2x 7.0 x lobeRt.frontal 6.11.5x 5.4 x 5616 3)Glioma (G lobeBasaltemporal X2.42.6X2.0 4317 3)Astrocytoma(G gangliaLt. 3.84.5x 3.2 x 1718 3)Anaplastic (G thalamusHypothalamusLt. 6.81.5x2.3x3.42.8X 5.7 x 919 gliomaAstrocytoma 4020 3)Astrocytoma(G lobeLt.pariétal 3.82.8x 3.4 x 5321 3)Astrocytoma(G lobeRt.frontal 3.42.8x 3.0 x 5122 3)Astrocytoma(G lobeLt.frontal 4.02.3x 3.2 x 6923 3)Récurrent (G lobeRt.témpora-parietal 5.22.6X 3.5 x 6624 astrocytoma(G lobeRt.fronto-parietal 4.33.2X 3.4 x 2)Astrocytoma 5625 2)Astrocytoma(G lobeLt.temporal 5.54.1x 4.7 x 2326 2)Astrocytoma(G lobeLt.témpora-parietal 7.13.9x 5.6 x 4727 2)Astrocytoma(G cerebellumLt. 4.62.6x 4.5 x 4828 2)Astrocytoma(G lobeRt.fronto-parietal 4.33.0X 4.2 X 6729 2)OligodendrogliomaOligoastrocytomaRécurrent(G lobeRt.temporal 3.81.0x 3.4 x 6830 lobeRt.frontal 1.6X2.02.2x 5331 lobeRt.frontal 3.73.0x 3.0 x 3632 2)MixedOligoastrocytomaMixedOligoastrocytomaGangliogliomaFibrillaryglioma (G lobeLt.frontal 5.64.7x 4.9 x 4933 lobeLt.temporal 5.32.0x 5.3 x 5934 lobeLt.frontal 3.01.2x 2.4 X 2235 lobeLt.temporal 1.6x2.64.1x 3036 astrocytomaRbrillary lobeLt.temporal 6.43.6x 5.3 X 3637 astrocytomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaMeningiomaRécurrentlobeRt.frontal 4.61.8x2.4x2.65.0X 4.2 X 4538 lobeTorcularF/T 7139 régionFaixPlural 6.02.8x 5.0 x 6640 3.61.4x2.1x 3.2 X 7341 lésionsPlural X2.32.8 lessionsPlural 3.80.7x 3.1 x lessionsRt.
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