Abstract
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Objectives: This study was designed to assess PET imaging using gastrin-releasing peptide receptor (GRPR) targeting tracers 68Ga-NOTA-Aca-BBN(7-14) and 68Ga-NOTA-IRDye800CW-BBN, in the detection and preoperative evaluation of glioma.
Methods: With institutional review board approval and written informed consent, 46 patients with suspected brain glioma as evaluated by contrast-enhanced MRI were recruited. Among the 46 patients, 34 patients received PET/CT and the other 12 patients received simultaneous PET/MR. A single dose of 74-148 MBq 68Ga-NOTA-Aca-BBN(7-14) or 68Ga-NOTA-IRDye800CW-BBN was injected intravenously. PET/CT and PET/MR scanning was performed at 30 min after the administration of 68Ga-NOTA-Aca-BBN(7-14), or at 30 min and 60 min after the administration of 68Ga-IRDye800CW-BBN. 3 patients accepted PET scanning with both 68Ga-NOTA-Aca-BBN(7-14) and 68Ga-IRDye800CW-BBN within one week for comparative analysis of the two tracers. Radioactivity concentrations and the mean and maximum standardized uptake values (SUVs) in these volumes of interest were obtained using the workstation software. For the patients who underwent PET/CT, PET images were co-registered to MR images with automatic image registration and manual positioning was performed. All the 46 patients underwent surgical removal of their tumor within 1 week after brain PET imaging. Among them, 24 patients also accepted GRPR targeting IRDye800CW-BBN NIRF intraoperatively. A final diagnosis was made based on the histopathologic examination with immunohistochemical staining of tumor samples against GRPR.
Results: Among the 46 patients, 80.4% (37/46) patients in this study were found positive tracer accumulation in brain lesions with excellent contrast from surrounding normal brain tissue on PET. Similar biodistributions between 68Ga-NOTA-Aca-BBN(7-14) and 68Ga-IRDye800CW-BBN PET were observed, while with additional uptake of brain blood pool on 68Ga-IRDye800CW-BBN PET at 30 and 60 min after tracer administration and lower uptake in normal brain tissues with the mean SUVs of 0.07 ± 0.03 (n=10) compared with 0.09 ± 0.04 (n=40) on 68Ga-NOTA-Aca-BBN(7-14) PET (P<0.05). 68Ga-NOTA-Aca-BBN(7-14) PET showed tracer accumulation in the 89.5% (34/38) lesions with pathological confirmed as WHO grade I optic pathway glioma in 6, WHO grade I ventricular ganglioglioma in 1, WHO grade II glioma in 3, WHO grade III glioma in 8, and WHO grade IV glioblastoma multiforme (GBM) in 16, with 100% (16/16) positive in GBM and uptake variation in overall glioma subtypes. Quantitative analysis yielded SUVmax and SUVmean values of 1.51 ± 0.57 and 1.19 ± 0.50, respectively, and tumor-to-background (T/B) ratios based on SUVmax and SUVmean were 21.0 ± 5.88 and 14.8 ± 3.01, respectively. 68Ga-IRDye800CW-BBN PET showed tracer accumulation in the 9/13 (69.2%) lesions with pathological confirmed as WHO grade I optic pathway glioma in 1, WHO grade III glioma in 1, and GBM in 7. Quantitative analysis yielded SUVmax and SUVmean values of 1.19 ± 0.47 and 0.98 ± 0.41, and T/B ratios of 15.30 ± 3.79 and 11.01 ± 2.33 at 30 min, and with SUVmax and SUVmean values of 0.95 ± 0.30 and 0.81 ± 0.25, T/B ratios of 17.10 ± 3.03 and 13.11 ± 2.01 at 60 min after injection, respectively. The lesion location matched well with MR alone and 36.5% (15/41) lesions exhibited additional larger enhancement (P<0.05) than MR with extent variation based on different cut off value. In the 24 patients who also accepted intraoperative IRDye800CW-BBN NIRF, 22 were both positive and the other 2 were negative on both PET and NIRF with pathological confirmed anaplastic astrocytoma and astrocytoma. Conclusion: This pilot study indicates that GRPR targeting 68Ga-NOTA-Aca-BBN (7-14) and 68Ga-NOTA-IRDye800CW-BBN PET imaging provides an ideal tool for the detection of glioma, which may be also useful for preoperative evaluation guiding surgery of glioma patients.