Abstract
491
Objectives: Glioma constitutes approximately 30% of the CNS tumors and approximately 80% of all the malignant brain tumors. The median survival in high grade glioma (GBM) is 15 months and the 5-year survival is approximately 10%. Magnetic resonance imaging (MRI) is the most commonly used procedure in the follow-up of such patients. However, molecular imaging (SPECT, PET) is often required for the tumor 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. Nevertheless, the clinical applications of 68Ga-labeled compounds are on the rise as this radionuclide has the potential for an on-demand production via generator technologies for routine production of various PET tracers without the need for expensive cyclotron operations. A strong association has been reported between CXCR4 chemokine receptor, with the development of an invasive phenotype in malignant GBM and eventually resulting in poor prognosis.
Methods: In this study, we used 68Ga-Pentixafor PET/CT for quantitative imaging of CXCR4 expression in GBM patients having clinical suspicion of recurrent/residual disease. Fourteen patients (8M: 6F; Mean Age- 51 ±12 yrs) with histopathologically proven GBM disease on surgical excised samples and with clinical suspicion of recurrent/residual GBM disease during post surgical follow-up were recruited prospectively. All the patients received radical radiotherapy (54.0-60.0 Gy) after surgery with or without concurrent temozolomide as indicated and underwent 68Ga-Pentixafor PET/CT and conventional ceMRI of the brain. About 110-150 MBq radioactivity of freshly prepared 68Ga-Pentixafor (synthesized by using Scintomics Germany, automated chemistry module, procured under DST-FIST Project Funding) was administered intravenously. Regional Brain CT (140Kv, 200mAs, Pitch 0.625:1, Slice thickness 2.5 mm) followed by PET acquisition (single bed position of 8min) at 1-hour post injection. Data was reconstructed using iterative method (2 iterations, 20 sub-sets) and interpreted both visually and semi-quantitatively.
Results: 68Ga-Pentixafor PET/CT findings with focally increased uptake of the radiotracer were interpreted as positive for recurrent/residual disease in 13/14 patients. The mean SUVmax value in these patients (n=13) was 5.25 ± 2.07 (range: 2.71 -9.69). PET/CT findings were concurrent with MRI findings in all the 14 patients. A representative 68Ga-Pentixafor PET image in a patient (58 yrs, Female) with recurrent tumor in central primary GBM disease showing intense uptake of the radiotracer (SUVmax=7.9) is presented in Figure-1. The only (1/14) patient who had no focal uptake anywhere in the brain on 68Ga-Pentixafor PET was interpreted as negative for any residual/recurrent disease. The ceMRI finding in this patient was also negative and reported as gliosis.
Conclusions: It has been proven in few recent preclinical and clinical studies (mainly multiple myeloma, isolated solid tumors including lung cancer) that 68Ga-Pentixafor uptake is tied up specifically to CXCR 4 expression. The results of this preliminary study demonstrate that 68Ga-Pentixafor PET imaging in GBM (know to have high CXCR4 expression) is viewed to open-up new theranostics applications (with beta and alpha radionuclides) for long term survival benefits. However, the diagnostic utility of this tracer needs to be validated in a large cohort of patients through multi-centric trials.
