Development of freeze-dried kit for the preparation of [99mTc]Tc-HYNIC-ALUG: A potential agent for imaging of prostate specific membrane antigen

Document Type : Original Article

Authors

1 Department of Chemistry, Government College University, Faisalabad, Pakistan

2 Isotope Production Division, Pakistan Institute of Nuclear Science and Technology, Nilore, Islamabad, Pakistan

3 Karachi Institute of Radiotherapy and Nuclear Medicine, Karachi, Pakistan

Abstract

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.

Keywords

Main Subjects

References

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