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In recent years, radionuclide-labeled prostate-specific membrane antigen (PSMA) ligands have been used in the diagnosis and treatment of prostate cancer
.
Studies have shown that 177Lu-labeled radioligand therapy (RLT) is a promising new therapy for metastatic castration-resistant prostate cancer (mCRPC) resistant to conventional therapy
.
At the 2021 ASCO conference, the results of the VISION study were announced.
Based on this, on March 23, the FDA approved the first RLT in the mCRPC field, 177Lu-PSMA-617
.
Coincidentally, recently, the efficacy and safety results of 177Lu-PSMA-I&T for mCRPC in an Asian population led by Professor Wang Feng from Nanjing First Hospital were published in the internationally renowned journal frontiers in oncology
.
The two studies corroborate each other and show the great therapeutic advantage of targeting PSMA radioligand therapy in the field of mCRPC
.
Yimaitong specially invited Professor Wang Feng, director of the Department of Nuclear Medicine of Nanjing First Hospital, to systematically interpret the current situation and application prospects of targeted PSMA radioligand therapy
.
Professor Wang Feng, Director of the Department of Nuclear Medicine, School of Imaging, Nanjing Medical University, MD Master/Ph.
D.
Supervisor, Director, Department of Nuclear Medicine, Nanjing First Hospital, Chairman of the 2019 International Conference on Radiopharmaceuticals and Therapy Deputy head of the Radiopharmaceutical Group of the Nuclear Medicine Branch of the Medical Association Chairman of the Nuclear Medicine Branch of the Jiangsu Medical Association Vice-chairman of the Nuclear Medicine Branch of the Jiangsu Medical Association Yimaitong: On March 23, based on the VISION study, the FDA approved 177Lu-PSMA-617, the first targeted radioligand therapy in the mCRPC field
.
This study is also known as a landmark research progress in the field of mCRPC.
Could you please talk about the efficacy of this therapy in mCRPC patients and how it affects the quality of life of mCRPC patients? Professor Wang Feng: After the release of the VISION study in June last year, it caused a great response.
The VISION study is mainly a clinical study on refractory prostate cancer or mCRPC in Europe
.
The study found that 46% of patients experienced a PSA drop of ≥50%, which is a very good outcome, while approximately 70% of patients achieved a PSA drop, and the majority of patients experienced improved quality of life
.
In terms of adverse events, only grade 1-2 myelosuppressive toxicity was found, and it can be said that the safety is very good
.
On March 23 this year, the FDA approved 177Lu-PSMA-617 for the treatment of mCRPC.
I think this is indeed a milestone.
Since 2015, VISION research has progressed very fast, and it only took about 6 years.
It has completely moved towards clinical translation, which is a very remarkable achievement
.
Yimaitong: Recently, the study "Efficacy and Safety of 177Lu-PSMA-I&T in East Asian Population" led by you was published in the internationally renowned journal frontiers in oncology.
Please talk about the targeted PSMA-I&T therapy in What is the efficacy and safety in Asian populations? What are the advantages in clinical application? Prof.
Feng Wang: First, 177Lu-PSMA-I&T is similar to 177Lu-PSMA-617 therapy.
The ligands of the two are different.
PSMA-I&T may be better than PSMA-617.
Second, the study we conducted was conducted in Asian populations.
The safety of PSMA-I&T is very good, especially the incidence of salivary gland damage is lower than that of the VISION study; thirdly, our study used individualized doses, although large doses were used treatment, but there were no major adverse events, only mild myelosuppression, leukopenia, and thrombocytopenia.
The patient will recover quickly after one month or one and a half months of treatment; fourth, the patient's quality of life is very Well, both studies have equally large advantages in terms of quality of life
.
The results of the "177Lu-PSMA-I&T" study are actually similar to those of the VISION study.
About 70% of the patients experienced a decrease in PSA, and the target lesions in two patients basically completely disappeared, which is a very good result
.
The PFS and OS results of this study are immature and the study is in further follow-up
.
In terms of clinical application, first, RLT can be combined with anti-androgen therapy, which may have better efficacy; second, compared with other chemotherapy, myelosuppression has less toxicity and is easily tolerated by patients; third, The incidence of adverse events is low, and it is easier to promote; fourth, compared with other therapies, such as new androgen receptor-targeted drugs such as enzalutamide, abiraterone, and apalutamide, the efficacy of RLT may be more significant
.
In clinical practice, we found that many patients experienced a decrease in PSA after one treatment.
Although these patients may also develop drug resistance after treatment, overall, the efficacy of RLT is still better than other treatments
.
In addition, in castration-sensitive prostate cancer, the therapy was more effective in patients with oligometastases and lymphoma metastases
.
Yimaitong: PSMA-I&T and PSMA-617 are both PSMA ligands.
What do you think of these two therapies after labeling with the labelable radionuclide 177Lu, 177Lu-PSMA-617 and 177Lu-PSMA-I&T? What are the advantages of the latter in clinical practice? Prof.
Wang Feng: PSMA-I&T and PSMA-617 are actually small molecule ligands of PSMA.
PSMA is highly expressed on the surface of most prostate tumor cells.
PSMA has folate hydrolase and glutamate carboxypeptidase activities.
PSMA ligands can be used as PSMA.
The substrate of PSMA has a high affinity with PSMA, and the PSMA substrate can bind to the extracellular domain of PSMA
.
The basic structure of PSMA-I&T and PSMA-617 are similar, but the chelating agent of the two is different.
I think that the salivary gland uptake of PSMA-I&T is a little less than that of PSMA-617, so there will be less damage to the salivary glands, so the patient's quality of life It will be higher, at least in terms of taste and so on
.
If the salivary glands are severely damaged, the patient has no sense of taste when eating
.
From this perspective, PSMA-I&T still has unique advantages
.
Second, at present, PSMA-I&T is easy to produce, and China can produce it
.
In this regard, PSMA-I&T also has certain advantages
.
Yimaitong: PSMA is considered to be an ideal target for the diagnosis and treatment of prostate cancer, and the small molecule inhibitors PSMA-I&T and PSMA-617 among PSMA ligands are considered to be the two most promising small molecules in the field of prostate cancer treatment.
Molecular inhibitors, what are the current problems and challenges in targeting PMSA radioligand therapy, and what are the future research directions? Prof.
Wang Feng: Generally speaking, PSMA-targeted radioligand therapy has opened up a precedent in the field of mCRPC treatment and brought a revolutionary change to the treatment of prostate cancer.
Moreover, PSMA-targeted radioligand therapy itself is based on PSMA precise imaging.
Precision medicine, it can be said, targeting PSMA radioligand therapy is the future direction of tumor treatment; second, its application can be more extensive, it can be used for neoadjuvant therapy, and it can also treat oligometastatic patients, providing more opportunities for subsequent surgical treatment.
Multiple opportunities and directions; third, the therapy can be combined with radiotherapy or chemotherapy or targeted therapy
.
Radioligand therapy will gradually become the cornerstone of prostate cancer treatment
.
In addition, after the therapy is approved by the FDA this year, it will definitely be included in the treatment guidelines for prostate cancer next year or the year after.
Compared with radiotherapy and chemotherapy, it is well tolerated and has great advantages in treatment
.
Edit: XY Review: XY Typesetting: Wenting Execution: XY Master Classroom, scan the code to enter ▼▼▼
.
Studies have shown that 177Lu-labeled radioligand therapy (RLT) is a promising new therapy for metastatic castration-resistant prostate cancer (mCRPC) resistant to conventional therapy
.
At the 2021 ASCO conference, the results of the VISION study were announced.
Based on this, on March 23, the FDA approved the first RLT in the mCRPC field, 177Lu-PSMA-617
.
Coincidentally, recently, the efficacy and safety results of 177Lu-PSMA-I&T for mCRPC in an Asian population led by Professor Wang Feng from Nanjing First Hospital were published in the internationally renowned journal frontiers in oncology
.
The two studies corroborate each other and show the great therapeutic advantage of targeting PSMA radioligand therapy in the field of mCRPC
.
Yimaitong specially invited Professor Wang Feng, director of the Department of Nuclear Medicine of Nanjing First Hospital, to systematically interpret the current situation and application prospects of targeted PSMA radioligand therapy
.
Professor Wang Feng, Director of the Department of Nuclear Medicine, School of Imaging, Nanjing Medical University, MD Master/Ph.
D.
Supervisor, Director, Department of Nuclear Medicine, Nanjing First Hospital, Chairman of the 2019 International Conference on Radiopharmaceuticals and Therapy Deputy head of the Radiopharmaceutical Group of the Nuclear Medicine Branch of the Medical Association Chairman of the Nuclear Medicine Branch of the Jiangsu Medical Association Vice-chairman of the Nuclear Medicine Branch of the Jiangsu Medical Association Yimaitong: On March 23, based on the VISION study, the FDA approved 177Lu-PSMA-617, the first targeted radioligand therapy in the mCRPC field
.
This study is also known as a landmark research progress in the field of mCRPC.
Could you please talk about the efficacy of this therapy in mCRPC patients and how it affects the quality of life of mCRPC patients? Professor Wang Feng: After the release of the VISION study in June last year, it caused a great response.
The VISION study is mainly a clinical study on refractory prostate cancer or mCRPC in Europe
.
The study found that 46% of patients experienced a PSA drop of ≥50%, which is a very good outcome, while approximately 70% of patients achieved a PSA drop, and the majority of patients experienced improved quality of life
.
In terms of adverse events, only grade 1-2 myelosuppressive toxicity was found, and it can be said that the safety is very good
.
On March 23 this year, the FDA approved 177Lu-PSMA-617 for the treatment of mCRPC.
I think this is indeed a milestone.
Since 2015, VISION research has progressed very fast, and it only took about 6 years.
It has completely moved towards clinical translation, which is a very remarkable achievement
.
Yimaitong: Recently, the study "Efficacy and Safety of 177Lu-PSMA-I&T in East Asian Population" led by you was published in the internationally renowned journal frontiers in oncology.
Please talk about the targeted PSMA-I&T therapy in What is the efficacy and safety in Asian populations? What are the advantages in clinical application? Prof.
Feng Wang: First, 177Lu-PSMA-I&T is similar to 177Lu-PSMA-617 therapy.
The ligands of the two are different.
PSMA-I&T may be better than PSMA-617.
Second, the study we conducted was conducted in Asian populations.
The safety of PSMA-I&T is very good, especially the incidence of salivary gland damage is lower than that of the VISION study; thirdly, our study used individualized doses, although large doses were used treatment, but there were no major adverse events, only mild myelosuppression, leukopenia, and thrombocytopenia.
The patient will recover quickly after one month or one and a half months of treatment; fourth, the patient's quality of life is very Well, both studies have equally large advantages in terms of quality of life
.
The results of the "177Lu-PSMA-I&T" study are actually similar to those of the VISION study.
About 70% of the patients experienced a decrease in PSA, and the target lesions in two patients basically completely disappeared, which is a very good result
.
The PFS and OS results of this study are immature and the study is in further follow-up
.
In terms of clinical application, first, RLT can be combined with anti-androgen therapy, which may have better efficacy; second, compared with other chemotherapy, myelosuppression has less toxicity and is easily tolerated by patients; third, The incidence of adverse events is low, and it is easier to promote; fourth, compared with other therapies, such as new androgen receptor-targeted drugs such as enzalutamide, abiraterone, and apalutamide, the efficacy of RLT may be more significant
.
In clinical practice, we found that many patients experienced a decrease in PSA after one treatment.
Although these patients may also develop drug resistance after treatment, overall, the efficacy of RLT is still better than other treatments
.
In addition, in castration-sensitive prostate cancer, the therapy was more effective in patients with oligometastases and lymphoma metastases
.
Yimaitong: PSMA-I&T and PSMA-617 are both PSMA ligands.
What do you think of these two therapies after labeling with the labelable radionuclide 177Lu, 177Lu-PSMA-617 and 177Lu-PSMA-I&T? What are the advantages of the latter in clinical practice? Prof.
Wang Feng: PSMA-I&T and PSMA-617 are actually small molecule ligands of PSMA.
PSMA is highly expressed on the surface of most prostate tumor cells.
PSMA has folate hydrolase and glutamate carboxypeptidase activities.
PSMA ligands can be used as PSMA.
The substrate of PSMA has a high affinity with PSMA, and the PSMA substrate can bind to the extracellular domain of PSMA
.
The basic structure of PSMA-I&T and PSMA-617 are similar, but the chelating agent of the two is different.
I think that the salivary gland uptake of PSMA-I&T is a little less than that of PSMA-617, so there will be less damage to the salivary glands, so the patient's quality of life It will be higher, at least in terms of taste and so on
.
If the salivary glands are severely damaged, the patient has no sense of taste when eating
.
From this perspective, PSMA-I&T still has unique advantages
.
Second, at present, PSMA-I&T is easy to produce, and China can produce it
.
In this regard, PSMA-I&T also has certain advantages
.
Yimaitong: PSMA is considered to be an ideal target for the diagnosis and treatment of prostate cancer, and the small molecule inhibitors PSMA-I&T and PSMA-617 among PSMA ligands are considered to be the two most promising small molecules in the field of prostate cancer treatment.
Molecular inhibitors, what are the current problems and challenges in targeting PMSA radioligand therapy, and what are the future research directions? Prof.
Wang Feng: Generally speaking, PSMA-targeted radioligand therapy has opened up a precedent in the field of mCRPC treatment and brought a revolutionary change to the treatment of prostate cancer.
Moreover, PSMA-targeted radioligand therapy itself is based on PSMA precise imaging.
Precision medicine, it can be said, targeting PSMA radioligand therapy is the future direction of tumor treatment; second, its application can be more extensive, it can be used for neoadjuvant therapy, and it can also treat oligometastatic patients, providing more opportunities for subsequent surgical treatment.
Multiple opportunities and directions; third, the therapy can be combined with radiotherapy or chemotherapy or targeted therapy
.
Radioligand therapy will gradually become the cornerstone of prostate cancer treatment
.
In addition, after the therapy is approved by the FDA this year, it will definitely be included in the treatment guidelines for prostate cancer next year or the year after.
Compared with radiotherapy and chemotherapy, it is well tolerated and has great advantages in treatment
.
Edit: XY Review: XY Typesetting: Wenting Execution: XY Master Classroom, scan the code to enter ▼▼▼
