Purpose of the Report
Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein, which is not only overexpressed in prostate cancers but also in variety of solid tumors including glioblastoma multiforme. The aim of the present study was to demonstrate PSMA expression in gliomas using 68Ga-PSMA-HBED-CC(PSMA 11) PET/CT.
Patients and Methods
Ten patients with initially MRI suspected and eventually histopathologically proven gliomas [8 males (age range 30–73 yr; mean age 51.8 yr); 2 females aged 39 and 55 years] were subjected preoperatively to regional brain PET scan with 68Ga-PSMA-11 and 18F-FDG PET/CT. Final histopathology of brain lesions, their MIB-1 proliferation index (MIB-1 PI) were compared with PSMA and FDG PET findings.
Results
FDG PET/CT showed distinct FDG uptake in high-grade gliomas, whereas low-grade gliomas were non-FDG-avid amidst physiological tracer uptake. In vivo PSMA expression was seen in all patients with glioma. Of these, the 7 patients of glioblastoma harboring 8 lesions showed significantly higher PSMA expression than those with low-grade gliomas, average SUVmax being 16.93 and 2.93, respectively. Similarly, average tumor-to-background ratios (13.95 and 3.42, respectively) and MIB-1 PI (17.31 and 3.3, respectively) were substantially more in high-grade versus low-grade gliomas.
Conclusions
The results of this pilot study show that 68Ga-HBED-CC-PSMA PET/CT can be used to characterize the PSMA expression in gliomas, high-grade ones demonstrating higher SUVmax, MIB-1 PI tumor-to-background ratio than the low-grade ones. With these results as basis, certain patients may benefit from potential PSMA-targeted radionuclide therapy.
Purpose of the Report
Prostate-specific membrane antigen (PSMA) is a member of superfamily of zinc-dependent exopeptidases that is robustly expressed in prostate cancer cells and nonprostatic solid tumor neovasculature including microvessels of thyroid tumors. Its expression in differentiated thyroid cancer (DTC) has been confirmed in many recent studies, but systematic studies exploring PSMA expression in patients with DTC with thyroglobulin elevation and negative iodine scintigraphy (TENIS) are lacking. The aim of the present study was to evaluate the role of PSMA scan in TENIS patients with DTC.
Methods
Nine consecutive patients with DTC with proven TENIS syndrome (6 men and 3 women with age range 29–68 years and mean age of 48 years) underwent 18F-FDG PET/CT as per the institution protocol. Thereafter, they were subjected to 68Ga-PSMA-HBED-CC PET/CT as per the institution protocol within a week of FDG PET imaging. Prostate-specific membrane antigen expression (SUVmax) in the lesions was compared with 18F-FDG PET and CT scan findings.
Results
In 5 of 9 patients with TENIS, the metastatic lesions showed PSMA expression. A total of 14 lesions were seen on the CT scan. Prostate-specific membrane antigen PET detected 9 of 14 lesions (64.28%) (SUVmax ranging from 10.1 to 45.67; median SUVmax of 16.31), whereas FDG PET was positive in 11 of 14 lesions (78.57%). The lesions that showed PSMA uptake was localized to bones (5 of 9) and lungs (4 of 9). Two lesions that were localized to iliac crest and acetabulum were missed on FDG PET but were seen on CT and PSMA PET scan.
Conclusions
The results of this pilot study indicate that 68Ga-HBED-CC-PSMA PET/CT demonstrates PSMA expression in TENIS patients with lesions being localized to the bones and lungs. 68Ga-PSMA PET/CT could be useful for the identification of TENIS patients who might benefit from PSMA-targeted radionuclide therapy.
The present investigation was aimed to evaluate the possibility of using diŠerent concentrations and polymeric grades of hydroxypropyl methylcellulose (K4M, K15M and K100M) for transdermal delivery of methotrexate, an immunosuppressant drug for rheumatoid arthritis. The matrixˆlms were evaluated for their physicochemical characterization followed by in vitro and in vivo evaluation. Selected formulations were subjected for their in vivo studies on healthy rabbits following balanced incomplete block design. The relevance of diŠerence in the in vitro dissolution rate proˆle and pharmacokinetic parameters (C max , t max , AUC (s) , t 1/2 , K el , and MRT) were evaluated statistically. The thickness and weight of the patch increased with the increase in polymeric grade and content. Fourier transform infrared spectroscopy and diŠerential scanning calorimetry results conˆrm that there is no interaction between drug and polymer used. X-ray diŠraction study reveals an amorphous state of drug in the matrixˆlms. The in vitro drug release followed Higuchi kinetics (r=0.972 997; p<0.001) as its coe‹cient of correlation values predominates over zero order andˆrst order release kinetics. In vitro dissolution proˆles and pharmacokinetic parameters showed a signiˆcant diŠerence between test products ( p<0.01), but not within test products. A quantitatively good correlation was found between per cent of drug absorbed from the transdermal patches and AUC (s) . A signiˆcant in vitro/in vivo correlation was observed when per cent drug released was correlated with serum drug concentration. Out of the various formulations made, the selected formulations are better in their in vitro dissolution and pharmacokinetic characteristics and thus hold potential for transdermal delivery.
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