Abstract
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Objectives: Glioma constitutes approximately 30% of the CNS tumours and approximately 80% of all the malignant brain tumours. Magnetic resonance imaging (MRI) is the most commonly used procedure in the follow-up of GBM patients. However, molecular imaging (SPECT, PET) is often required for the tumour characterization and detection of active recurrent/residual disease. The currently available PET tracers i.e. 18F-FET and 11C-methionine have proven high diagnostic efficacy in GBM. A strong association has been reported between CXCR4 chemokine receptors, with the development of an invasive phenotype in malignant GBM and eventually resulting in poor prognosis. The aim of this study was to evaluate the patient outcome with escalated radiation dose derived from the accurate residual/ recurrent glioma disease mapping using CXCR4 targeting 68 Ga-Pentixafor PET imaging.
Methods: 68Ga-Pentixafor PET/CT imaging was performed in 9 patients (7M; 2F; mean age =54.3±8.9 years) at a single point pre-operatively. Tissue diagnosis in 7/9 patients was made on fixed tumor tissue and CXCR4 receptors’ expression was documented by IHC using anti-CXCR4 antibody and visual quantitative scoring. In the 11 (6M:5F; mean age = 44.3±11.7 years) patients, who presented for the clinical/radiological suspicion of recurrence/residual disease, 68Ga-Pentixafor PET/CT imaging was done at presentation (baseline) and at 3-mo post radiation treatment. About 110-150 MBq radioactivity of freshly prepared 68Ga-Pentixafor was administered intravenously. After the scan evidence of recurrent/residual disease, all these 11 patients received radical radiotherapy (67.0 Gy - escalation of 7.0 Gy) with or without concurrent temozolomide as indicated. Regional Brain CT (140Kv, 200mAs, Pitch 0.625:1, Slice thickness 2.5 mm) followed by PET acquisition (single bed position, 8min) at 1-hour post injection. Data was reconstructed using iterative method (2 iterations, 20 sub-sets) and interpreted both visually and semi-quantitatively. All the patients (n=20) underwent contrast enhanced MRI (ceMRI) and MR spectroscopy (MRS) and the data was analysed for visual scan interpretation and quantitative tumour metabolites (choline/NAA; choline/creatine) ratios.
Results: 68Ga-Pentixafor PET/CT findings with focally increased uptake of the radiotracer were interpreted as positive (Figure-1) for primary tumour in 9/9 patients in the pre-surgery group with histopathological/IHC disease evidence in 7/9 patients. The CeMRI findings were positive in 9/9 patients. The metabolites’ ratios of i.e. choline/NAA; choline/creatine on MRS were 4.82±2.5 and 3.0±2.6 respectively.The mean values (n=7) for 68Ga-Pentixafor PET/CT quantitative parameters i.e. SUVmax, SUVmean, SUVpeak, T/B ratio were 4.5±1.6, 0.6±0.26, 1.95±0.8, 6.8 ±4.5 respectively. In the post-surgery group of patients, all the patients (n=11) showed scan evidence of disease recurrence with focally increased tracer uptake. However, no significant difference was observed in the mean values of quantitative parameters (SUVmax, SUVmean, SUVpeak) between the baseline and the 3-mo post RT follow-up PET imaging (Figure-2). Likewise, no significant difference was observed for Cho/NAA; Choline/creatine ratios on MRS imaging. Conclusion: 68Ga-Pentixafor concentrated preferentially in the primary GBM tumours and this preliminary study thus indicates that the specific binding affinity of this tracer may help in the development of CXCR4 targeting radiotherapeutics (alpha/beta emitters). The diagnostic utility of this tracer for response assessment to chemo/radiotherapy and for overall prognostication however, needs to be established in a larger cohort of patients with clinical follow-up and repeat CXCR4 based imaging beyond 3-months.
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