Evaluation of Radiation dosimetry of 99mTc-HYNIC-PSMA and imaging in prostate cancer

Abstract

This study aims to evaluate the radiation dosimetry of a new technetium-99m-labelled small-molecule inhibitor of prostate-specific membrane antigen (HYNIC-Glu-Urea-A, 99m tc-HYnic-pSMA) and its feasibility as a tumor-imaging agent in prostate cancer (PCa) patients. A total of 15 PCa patients were enrolled in this study. For the dosimetry study, 5 PCa patients received whole-body planar scans at 0.5 h, 1 h, 2 h, 4 h and 8 h after 99m Tc-HYNIC-PSMA injection. The Dosimetry Toolkit (GE, Milwaukee) was used to process the data and segment the organs in the SPECT/CT images, which were then projected onto planar images. The organ-specific absorbed doses, total-body absorbed doses and 99m tc-HYnic-PSMA effective doses of patients were calculated using OLINDA/EXM 1.1 software. Whole-body SPECT/ CT images were also acquired from additional 10 prostate patients to investigate the feasibility of 99m tc-HYNIC-PSMA for imaging tumors by calculating the ratio of tumor-to-background tracer uptake at 2 h after 740 MBq administration. The total-body absorbed dose was 1.54E-03 ± 2.43E-04 mGy/MBq, and the effective dose was 3.72E-03 ± 4.5E-04 mSv/MBq. Compared to published studies of other similar pSMA tracers and 99m Tc-targeted conventional tracers, the absorbed doses of 99m tc-HYnic-pSMA in all organs showed that it could be used safely in the human body. In addition, 99m tc-HYnic-pSMA showed high tracer uptake (with a tumor-to-background ratio of 9.42 ± 2.62) in the malignant lesions of PCa patients, making it a promising radiopharmaceutical imaging method for site-specific management of PCa.

Dose estimates of occupational radiation exposure during radioguided surgery of Tc-99m-PSMA-labeled lymph nodes in recurrent prostate cancer

“…With 4.15 ± 0.86 h, the observed effective half-life of [ 99m Tc]Tc-PSMA-I&S is significantly below the physical half-life of 99m Tc. A recent study analyzed the internal radiation exposure of [ 99m Tc]Tc-HYNIC-PSMA, which exhibits a similar biodistribution as [ 99m Tc]Tc-PSMA-I&S as it is also excreted mainly through the urinary system [12]. By means of whole-body scintigraphies up to 8 h p. i. the colleagues observed an effective half-life [ 99m Tc]Tc-HY-NIC-PSMA of clearly < 4 h which is in line with our result of 4.15 h derived from dose rate measurements.…”

One-step, kit-based radiopharmaceuticals for molecular SPECT imaging: a versatile diphosphine chelator for 99mTc radiolabelling of peptides

“…This contrasts existing molecular 99m Tc radiotracers that have recently entered late-stage clinical trials, such as 99m Tc-MIP-1404, which requires (i) radiochemical synthesis of fac-[ 99m Tc(CO)3(H2O)3] + , prior to (ii) reaction with the tridentate MIP-1404 chelator-peptide, and (iii) further purification and formulation before administration. 6 Additionally, the coordination sphere of [ 99m TcO2(DP-RGD)2] + is structurally well-defined; the structures of other recently described 99m Tc radiopharmaceuticals based on the HYNIC chelator (such as 99m Tc-3PRGD2 9 and 99m Tc-HYNIC-PSMA, 10 which have both demonstrated clinical utility), are more ambiguous. 11,12 We are currently developing new diphosphine-peptide bioconjugates based on BMA, and further optimising kit-based 99m Tc-radiolabelling of such derivatives.…”

“…8 Co-ligands such as ethylenediamine or tricine occupy remaining coordination sites on the Tc. Some of these HYNIC-based radiopharmaceuticals can be prepared from a single kit, 9,10 but their structures remain ill-defined: it is unknown whether HYNIC coordinates to Tc via the hydrazino group only, or as a bidentate ligand, via the hydrazino and pyridyl groups. 11,12 The radiopharmaceutical "Myoview" is used to image cardiac perfusion.…”

Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging

“…In this regard, scintigraphic imaging can be used for the tracking of gamma-emitting (photon) radionuclide compounds in vivo for diagnostic and therapeutic purposes (Boerman et al, 2000;Patel et al, 2016). The γ-ray emissions from the radionuclides can be detected by singlephoton emission computed tomography (SPECT) to construct an image or be used to estimate radiation dosimetry (Jackson et al, 2020;Zhang et al, 2020).…”