Guru Bandopadhyaya

13N-Ammonia PET/CT for detection of recurrent glioma: a prospective comparison with contrast-enhanced MRI.

PurposeWe assessed the value of 13N-ammonia PET-computed tomography (PET/CT) in recurrent glioma and compared the results with those of contrast-enhanced MRI (CE MRI). Materials and methodsFifty-two (mean age, 39.8±11.6 years; male, 33; female, 19) histopathologically proven and previously treated glioma patients with clinical suspicion of recurrence were evaluated with 13N-ammonia PET/CT and CE MRI. PET/CT images were evaluated qualitatively and quantitatively (maximum standardized uptake value). Tumour to white matter (T/W), tumour to grey matter (T/G) and tumour to pituitary (T/P) ratios were calculated and cutoff levels were derived with receiver operating characteristic curve analysis. Sensitivity, specificity and predictive values were compared. A combination of clinical follow-up, repeat imaging and biopsy (when available) was taken as the reference standard. ResultsOn the basis of the reference standard, 23 out of 52 patients were seen to have recurrence. Overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 13N-ammonia PET/CT were 82.6, 86.2, 82.6, 86.2 and 84.6%, respectively, whereas those of CE MRI were 96.7, 48.3, 59.5, 93.3 and 69.2%, respectively. Overall, 13N-ammonia PET/CT was statistically superior to CE MRI (P=0.001). In low-grade tumours, 13N-ammonia PET/CT performed better than MRI with an accuracy of 86.8 versus 68.4% (P=0.003). In high-grade tumours, both the modalities had comparable performances with accuracies of 78.6% for 13N-ammonia PET/CT and 71.4% for CE MRI (P=0.250). Among the ratios, T/P was the most useful, with the largest area under the curve (0.825; P=0.0001). Conclusion13N-Ammonia PET/CT shows higher accuracy compared with contrast-enhanced MRI for detecting recurrent gliomas, particularly in low-grade tumours.

Tamoxifen–2-hydroxylpropyl-β-cyclodextrin-aggregated nanoassembly for nonbreast estrogen-receptor-positive cancer therapy

BACKGROUND Tamoxifen (Tam) is used for the treatment and prevention of estrogen-receptor-positive human breast and other cancers. Its use in ovarian cancer has not been well studied. METHOD We formulated and characterized a water-soluble Tam-2-hydroxylpropyl-beta-cyclodextrin (HPbetaCD; 1:2 M) complex. RESULTS The differential scanning calorimetery of Tam-HPbetaCD indicated the transition of Tam from crystalline to amorphous form on addition of HPbetaCD. (1)H-nuclear magnetic resonance nuclear overhauser effect cross-peaks between phenyl moieties of Tam and HPbetaCD, and downfield shifts in H-3 (0.26) and H-5 (0.29) protons of HPbetaCD suggested the inclusion of Tam in HPbetaCD cavity. Transmission-electron microscopy studies of HPbetaCD and the Tam-HPbetaCD complex revealed the formation of aggregated nanoassembly at 60-180 nm. Dimethyl thiazol diphenyltetrazolium bromide assay demonstrated 7.37 +/- 2.32% cell survival of OAW-42 cells with 3 microg/ml Tam concentration. CONCLUSION The Tam-HPbetaCD nanoassembly entered the cell owing to enhanced permeability and retention property of tumor cell and antiestrogenic Tam and, therefore, resulted in excellent anticancer efficacy in the ovarian cancer cell line.

Nanotamoxifen delivery system: Toxicity assessment after oral administration and biodistribution study after intravenous delivery of radiolabeled nanotamoxifen

Tamoxifen is the most prescribed anticancer oral drug for increasing overall survival and decreasing recurrence and the risk of contralateral disease. However, some side effects, such as endometrial and liver tumors, thromboembolic disorders, and drug resistance, are associated with long-term tamoxifen treatment. We assessed the hematologic and organ toxicity after oral administration of three different doses of nanotamoxifen formulations. We also performed biodistribution studies of Technetium-99m (99mTc)-nanotamoxifen after intravenous administration. The results demonstrated that nanotamoxifen was well-tolerated, with no adverse effect on biochemical parameters of blood and at the cellular level. Nitric oxide (NO) levels indicated no free radical formation. Oral nanotamoxifen is well-tolerated, with no hepatic or renal toxicity. Intravenous nanotamoxifen has potential to escape the liver, and is known for producing the harmful metabolite 4-hydroxytamoxifen (4OH-tamoxifen), which can cause uterine cancer.