Development of freeze-dried kit for the preparation of [99mTc]Tc-HYNIC-ALUG: A potential agent for imaging of prostate specific membrane antigen
نویسندگان
1 Department of Chemistry, Government College University, Faisalabad, Pakistan
2 Isotope Production Division, Pakistan Institute of Nuclear Science and Technology, Nilore, Islamabad, Pakistan
3 Department of Chemistry, Government College University, Faisalabad, Pakistan
4 Department of Chemistry, Government College University, Faisalabad, Pakistan
5 Department of Chemistry, Government College University, Faisalabad, Pakistan
6 Isotope Production Division, Pakistan Institute of Nuclear Science and Technology, Nilore, Islamabad, Pakistan
7 Department of Chemistry, Government College University, Faisalabad, Pakistan
8 Karachi Institute of Radiotherapy and Nuclear Medicine, Karachi, Pakistan
9 Karachi Institute of Radiotherapy and Nuclear Medicine, Karachi, Pakistan
10 Department of Chemistry, Government College University, Faisalabad, Pakistan
11 Isotope Production Division, Pakistan Institute of Nuclear Science and Technology, Nilore, Islamabad, Pakistan
doi
10.22034/irjnm.2024.129413.1577چکیده
Introduction: Prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of Prostate cancer (PCa). In this study, we introduce the freeze-dried kit formulation of [99mTc]Tc-HYNICALUG for easy clinical evaluation of prostate cancer.Methods: In this work, an in silico modeling of the urea-based PSMA small molecule (HYNIC-ALUG) was performed to check its interaction with human glutamate carboxypeptidase II and compared it with experimental results. The HYNIC-PSMA kit was formulated for easy preparation of [99mTc]Tc-HYNIC-ALUG. The kit contained a freeze-dried mixture of HYNIC-ALUG, coligands SnCl2.2H2O, and antioxidant D-mannitol.Results: The calculated Ki value (inhibition/dissociation constant) was 4.55 which showed excellent binding affinity of HYNIC-ALUG with PSMA. miLogP and cLogS values are -4.04 and -3.07 respectively showing its hydrophilic character and predicting its excellent distribution in biological fluids. Subsequently, the radiochemical purity of the HYNIC-PSMA kit was 99.1 ± 1.32% (n = 6) determined by radio-ITLC and by HPLC as well. In vitro stability in saline and serum was studied up to 4 h and showed high stability (≥ 96%). The distribution of [99mTc]Tc-HYNIC-ALUG was carried out in two patients and SPECT/CT planar images were acquired at 2h and 4h respectively. Bio-physiological distribution of [99mTc]Tc-HYNIC-ALUG was observed normally in lacrimal, salivary glands, liver, spleen, gut, kidneys, and urinary bladder.Conclusion: The HYNIC-ALUG freeze-dried kit could be used for easy preparation of [99mTc]Tc-HYNIC-ALUG and can be considered as a potential agent for the diagnosis, staging, and restaging of advanced prostate cancer.
