scholarly journals Modular Approaches in PET-tracer Development: Radiotracer Design, Synthesis and Automation for Prostate Cancer and Heart Failure

2020 ◽  
Author(s):  
◽  
Verena Böhmer
2021 ◽  
Vol 14 (3) ◽  
pp. 188
Author(s):  
Ines Katzschmann ◽  
Heike Marx ◽  
Klaus Kopka ◽  
Ute Hennrich

For the PET imaging of prostate cancer, radiotracers targeting the prostate-specific membrane antigen (PSMA) are nowadays used in clinical practice. [18F]PSMA-1007, a radiopharmaceutical labeled with fluorine-18, has excellent properties for the detection of prostate cancer. Essential for the human use of a radiotracer is its production and quality control under GMP-compliance. For this purpose, all analytical methods have to be validated. [18F]PSMA-1007 is easily radiosynthesized in a one-step procedure and isolated using solid phase extraction (SPE) cartridges followed by formulation of a buffered injection solution and for the determination of its chemical and radiochemical purity a robust, fast and reliable quality control method using radio-HPLC is necessary. After development and optimizations overcoming problems in reproducibility, the here described radio-HPLC method fulfills all acceptance criteria—for e.g., specificity, linearity, and accuracy—and is therefore well suited for the routine quality control of [18F]PSMA-1007 before release of the radiopharmaceutical. Recently a European Pharmacopeia monograph for [18F]PSMA-1007 was published suggesting a different radio-HPLC method for the determination of its chemical and radiochemical purity. Since the here described method has certain advantages, not least of all easier technical implementation, it can be an attractive alternative to the monograph method. The here described method was successfully validated on several radio-HPLC systems in our lab and used for the analysis of more than 60 batches of [18F]PSMA-1007. Using this method, the chemical and radiochemical purity of [18F]PSMA-1007 can routinely be evaluated assuring patient safety.


2014 ◽  
Vol 111 (20) ◽  
pp. 7254-7259 ◽  
Author(s):  
N. T. Viola-Villegas ◽  
S. D. Carlin ◽  
E. Ackerstaff ◽  
K. K. Sevak ◽  
V. Divilov ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Bishesh Shrestha ◽  
Sugam Gouli ◽  
Asis Shrestha

Introduction: Prostate cancer is the second most common cancer in males. Its risk increases with age. So does the risk for cardiovascular disease. Androgen receptor-targeted therapy is now recommended to be added to androgen-deprivation therapy in the treatment of prostate cancer. We present common cardiovascular adverse events seen with the use of anti-androgens medication: abiraterone, enzalutamide, apalutamide, and darolutamide. Methods: We conducted a meta-analysis of 13 multinational randomized phase III clinical trials looking for cardiovascular adverse events in groups that received abiraterone, enzalutamide, apalutamide and darolutamide for treatment of prostate cancer. We analyzed a cohort of 9867 patients in these trials. Results: In the abiraterone usage group (n= 3492), most common cardiovascular adverse event was hypertension reported in 16.03%. Atrial fibrillation was reported in 0.97% and other cardiovascular events (IHD, MI, SVT, VT, and heart failure) were seen in 9.56%. In the enzalutamide usage group (n=4094) hypertension was seen in 10.6%, IHD in 1.88%, and atrial fibrillation was seen in 0.39%. Other unspecified cardiovascular adverse events were reported in 5.98%. In the apalutamide usage group (n=1327) hypertension was seen in 22%. Other cardiovascular adverse events (atrial fibrillation, MI, cardiogenic shock) were seen in 0.96%. In the darolutamide usage group (n=954) hypertension was seen in 6.6%, coronary artery disorders (coronary artery disease, coronary artery occlusion and stenosis) in 3.24%, and heart failure in 1.88%. Conclusions: The most common cardiovascular adverse event with use of anti-androgen medication seen in this large cohort analysis was hypertension with highest incidence seen in apalutamide group. Other cardiovascular side-effects noted were atrial fibrillation, SVT, VT, ischemic heart disease, MI, heart failure, and cardiogenic shock. Abiraterone and enzalutamide are the drugs that have been used in most trials. FDA adverse reaction reporting system (FAERS) shows hypertension as the most commonly reported cardiovascular adverse event with abiraterone and enzalutamide use. More prospective studies are needed to further access cardiovascular risk with use of anti-androgen therapy.


Author(s):  
Xin Chen ◽  
Changqing Xu ◽  
Yuxia Li ◽  
Xiaoming Duan ◽  
Guisen Zhao

Background: The androgen receptor (AR) signaling functions is a critical driving force for the progression of prostate cancer (PCa) to bring about anti-prostate cancer agents, and AR has been proved to be an effective therapeutic target even for castration-resistant prostate cancer (CRPC). Objective: In order to discover novel anti prostate cancer agents, we performed structural modifications based on the lead compounds T3 and 10e.Methods: A set of 1-methyl- 1H-pyrazole-5-carboxamide derivatives were synthesized and evaluated for their inhibitory activities against both expressions of prostate-specific antigen(PSA) and growth of PCa cell lines. Results: Compound H24 was found to be able to completely block PSA expression at 10 µM, and showed prominent antiproliferative activity in both the LNCaP cell line (GI 50 = 7.73 µM) and PC-3 cell line (GI 50 = 7.07 µM). Conclusions: These preliminary data supported a further evaluation of compound H24 as a potential agent to treat prostate cancer.


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