ABSTRACT
Purpose@#177Lu-DKFZ-PSMA-617 is a promising treatment for patients with metastatic prostate cancer. Specific dosimetry for each patient is an important factor in planning the patient’s treatment process. This study aimed to perform an image-based absorbed dose calculation for the treatment of metastatic prostate cancer with 177Lu-DKFZ-PSMA-617. @*Methods@#The individualized patient dosimetry calculations were based on whole-body planar scintigraphy images acquired in 10 patients with a mean age of 71.4 ± 6.07 years (range 63–85 years) at approximately 0–2 h, 4–6 h, 18–24 h, and 36–48 h after administration of the mean 6253 ± 826.4 MBq (range 5500–7400 MBq) of 177Lu-DKFZ-PSMA-617. Time-activity curves were generated for various organs. For count conversion to activities, calibration factors were calculated. Finally, the absorbed dose for an individual cycle was calculated using IDIAC-DOSE 2.1 software. @*Results@#On average, the calculated absorbed dose for the kidneys and salivary glands were 0.46 ± 0.09 mGy/MBq and 0.62 ± 0.07 mGy/MBq, respectively. @*Conclusions@#Based on the results, the 177 Lu-PSMA-617 therapy is a safe method for the treatment of castration-resistant prostate cancer patients. Large inter-individual variations in organ dose were found, demonstrating the need for patientspecific dosimetry and treatment planning.
ABSTRACT
The secreted aspartic proteinases [Sap2] of Candida albicans has prominent role on Candida adherence, invasion, and pathogenicity. The aim of this study was cloning, expression and characterizing of Sap2 enzyme. Also in this study for the first time, the expression system P. pasturis was used for expressing the recombinant protein. C. albicans Sap2 gene was amplified by PCR with sticky ends, EcoR1 and SacII, and it was subcloned into the T/A vector. The sequencing of this gene was done with universal primers and then the Sap2 gene was cloned into pGAPZ?A expression vector. The construct was transformed into P. pasturis yeast; the Sap2 gene integration into the yeast genome was accomplished by the homologous recombination. The expressed protein was confirmed by western blotting using monoclonal antibody against Sap2 protein. Finally, the recombinant protein was purified by Ni-NTA chromatography column, and the activity of the enzyme was confirmed. In this study, we successfully amplified C. albicans Sap2 gene and subsequently integrated into the yeast pichia pasturis genome by homologous recombination. Moreover, we were able to identify a yeast clone secreting the recombinant protein. The optimum over expression of sap2 protein was obtained after 96 h, at 30 C. Expression of Sap2 gene in P. pasturis, in comparison to bacterial expression system, leads to a high-level expression, and also need for post translation modifications, that might be required for the activity of enzyme, is obviated in the yeast system. Based on our results, the purified acid aspartyl proteinase purified from P. pasturis was capable of degrading BSA as a substrate in-vitro. The recombinant Sap2 protein had maximum activity in an acidic pH