Prostate cancer is the third most common cause of cancer death in men. Most patients with localized prostate cancer will be cured with surgery or radiation therapy, but up to 35% of patients will have their prostate cancer return.Current conventional imaging modalities have limitations particularly at low prostate specific antigen levels. This study proposes to use 68Ga-HTK03149 Dynamic Whole Body (DWB) Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI) scans which targets prostate-specific membrane antigens (PSMA) to detect where in the body the prostate cancer has recurred.

开始日期2025-08-01

申办/合作机构

British Columbia Cancer Agency

NCT05570994 / Recruiting临床1/2期IIT

A Phase I/II Study of 177Lu-HTK03170 in Metastatic, Castration-Resistant Prostate Cancer Subjects With Prostate-specific Membrane Antigen-positive Disease

This study will determine the safe initial injected activity of the radioligand therapy 177Lu-HTK03170 for the measurement of dosimetry and initiation of treatment in subjects with PSMA-positive, metastatic castrate resistant prostate cancer, (mCRPC). Subjects will receive treatment which will be escalated between cycles and personalized based on dosimetry calculations and imaging. In addition, antitumour activity will be measured by radiographic response, and further assessments of the treatment will be measured by CT imaging, ctDNA/ctRNA, PSA, PSMA PET/CT, and quality of life questionnaires. Subjects will be followed for 2 years or until they have progression and are switched to another systemic treatment.

开始日期2024-01-01

申办/合作机构

British Columbia Cancer Agency

NCT04831307 / Unknown statusN/AIIT

Evaluation of the in Vivo Biodistribution and Radiation Dosimetry of 68Ga-HTK03149 for Use as a Diagnostic Radiopharmaceutical

This is a preliminary evaluation of a radiotracer's biodistribution in human subjects. It is a prospective, single-centre, open-label, single group assignment interventional study.
Prostate cancer is very common, and PSMA imaging is currently the most accurate means of localizing these tumours.
The goal is to evaluate the biodistribution and safety of [68Ga]HTK03149 PET/CT for prostate cancer imaging.

开始日期2021-08-30

申办/合作机构

British Columbia Cancer Agency

100 项与 68Ga-HTK03149 相关的临床结果

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100 项与 68Ga-HTK03149 相关的转化医学

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100 项与 68Ga-HTK03149 相关的专利（医药）

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项与 68Ga-HTK03149 相关的文献（医药）

2022-01-01·Theranostics

What a difference a methylene makes: replacing Glu with Asp or Aad in the Lys-urea-Glu pharmacophore of PSMA-targeting radioligands to reduce kidney and salivary gland uptake

Article

作者: Lin, Kuo-Shyan ; Bénard, François ; Kuo, Hsiou-Ting ; Uribe, Carlos F ; Roxin, Aron ; Zhang, Chengcheng ; Zhang, Zhengxing ; Tan, Ruiyan ; Merkens, Helen

The aim of this study was to investigate the effect of replacing Glu in the Lys-urea-Glu PSMA-targeting pharmacophore of [⁶⁸Ga]Ga-HTK03041 with a close analog on the uptake of kidneys, salivary glands and PSMA-expressing tumor xenografts. Methods: HTK03161, HTK03149 and HTK03189A/B were obtained by replacing Glu in HTK03041 with Asp, Aad (L-2-aminoadipic acid) and Api (2-aminopimelic acid), respectively. PSMA binding affinities were measured by competition binding assays. PET imaging and biodistribution studies of ⁶⁸Ga-labeled ligands were performed in LNCaP tumor-bearing mice. The best candidate HTK03149 was selected and radiolabeled with ¹⁷⁷Lu, and SPECT imaging and biodistribution studies were performed in LNCaP tumor-bearing mice. Radiation dosimetry calculation was conducted using the OLINDA software. Radioligand therapy study was performed in LNCaP tumor-bearing mice treated with [¹⁷⁷Lu]Lu-HTK03149 (9.3-148 MBq), [¹⁷⁷Lu]Lu-PSMA-617 (37 MBq) or ^natLu-HTK03149 (500 pmol). Results: PSMA binding affinities (K_i) of Ga-HTK03161, Ga-HTK03149, Ga-HTK03189A and Lu-HTK03149 were 3.88±0.66, 6.99±0.80, 550±35.7 and 1.57±0.42 nM, respectively. PET imaging showed that all ⁶⁸Ga-labeled HTK03161, HTK03149 and HTK03189A/B were excreted mainly via the renal pathway and had minimal uptake in all organs/tissues including kidneys and salivary glands. Tumor xenografts were clearly visualized in PET images of [⁶⁸Ga]Ga-HTK03161 and [⁶⁸Ga]Ga-HTK03149 but were barely visualized using [⁶⁸Ga]Ga-HTK03189A/B. Tumor uptake values for [⁶⁸Ga]Ga-HTK03161, [⁶⁸Ga]Ga-HTK03149, [⁶⁸Ga]Ga-HTK0189A and [⁶⁸Ga]Ga-HTK03189B were 12.7±1.91, 19.1±6.37, 2.10±0.28 and 0.67±0.15 %IA/g, respectively at 1h post-injection, and their average kidney and salivary gland uptake values were 2.13-4.41 and 0.20-0.23 %IA/g, respectively. Longitudinal SPECT imaging studies showed that [¹⁷⁷Lu]Lu-HTK03149 was excreted mainly through the renal pathway with high uptake in LNCaP tumors and minimal uptake in all normal organs/tissues. The tumor uptake of [¹⁷⁷Lu]Lu-HTK03149 peaked at 4h post-injection (20.9±2.99 %IA/g) and the uptake was sustained over time. Compared to [¹⁷⁷Lu]Lu-PSMA-617, [¹⁷⁷Lu]Lu-HTK03149 had 145% increase in tumor absorbed dose but 70% less in kidney absorbed dose, leading to an 7.1-fold increase in tumor-to-kidney absorbed dose ratio. Radioligand therapy studies showed that only half of the [¹⁷⁷Lu]Lu-PSMA-617 injected dosage was needed for [¹⁷⁷Lu]Lu-HTK03149 to achieve the same median survival. Conclusion: Replacing Glu in the PSMA-targeting Lys-urea-Glu pharmacophore of [⁶⁸Ga]Ga-HTK03041 with Asp and Aad generates [⁶⁸Ga]Ga-HTK03161 and [⁶⁸Ga]Ga-HTK03149, respectively, and the new derivatives retain high uptake in LNCaP tumors and have minimal uptake in normal organs/tissues including kidneys and salivary glands. [¹⁷⁷Lu]Lu-HTK03149 also retain high uptake in LNCaP tumors and has minimal uptake in normal organs/tissues, and is, therefore, promising for clinical translation to treat prostate cancer.

100 项与 68Ga-HTK03149 相关的药物交易

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