RE:Lutetium in NYTimes this morningWino,
It targets a protein, not a gene. It would be very easy to attach Lu177 or Ga68 to TH19P01. Actually, it can be made through what is called a peptide bond. So the reaction between an amino group (NH2) and a carboxylic acid (COOH) to form CONH +H2O. The same bond that allows linking amino acids in peptides or proteins. The DOTA linker used in Dotatate, has four carboxylic acid groups, and TH19P01 has at least two free amino group, maybe three.
I know I said it here numerous times, but it would be so easy for Thera to at least make the preliminary work on that with Gallium 68. A radioisotope emitting only positrons. University of Sherbrooke here in the province of Quebec are working on that. Thera would only need to provide the with the peptide with the linker on it and they would put Gallium 68 on the linker. Then you inject it to a cancer xenograft mouse and do a PET scan.
The imaging part with Ga68 would be the first step. If all goes well, then the door would be open to replicate it with Lu177, and in the future, with Actinium 225. Is there somebody at Thera reading this board? Not sure after all the cr*p written here about them in the last few months. That being said, they are competent, so I am sure they are aware of the radioisotopes possibilities. They probably wait for the proof of concept in humans and much more money coming in before starting other things.
Wino115 wrote: Lutetium made the NYTimes this morning. This only targets a gene seen on the prostate so you'd need another target to use it for other tumors....Sortilin here we come! I gather from JFM you could attach Lute to the TH peptide.
New Therapy for Aggressive Prostate Cancer Improves Survival
The experimental treatment relies on radioactive molecules that seek out tumor cells, a strategy that may be useful against other cancers.
Among men who received the new therapy, there was a nearly 40 percent reduction in deaths over the course of the clinical trial, compared with similar patients who received only standard treatment, researchers reported on Wednesday.
Prostate cancer is the second-leading cause of cancer death among American men, after lung cancer; an estimated 34,130 men will die of prostate cancer this year. One in eight men will be diagnosed with the disease at some point in their lives. The risk increases with age, and the cancer is more common in Black men.
The new treatment relies on a radioactive molecule to target a protein found on the surface of prostate cancer cells. The study, which followed 831 patients with advanced disease in 10 countries for a median period of 20 months, was published in The New England Journal of Medicine.
“This is something new — you’re driving radiation right to the cancer itself,” said Karen Knudsen, president and chief executive of the American Cancer Society. “It’s a much more sophisticated strategy for targeting the tumor.”
“You’re not just destroying the cancer cells — you’re smart-bombing the place that the tumor has found for itself to live.”
There is no definitive cure for metastatic prostate cancer, and there is an urgent need for new therapies, Dr. Knudsen said. Most life-extending treatments rely on suppressing or blocking androgens, the male hormones that fuel prostate cancer.
“This opens the door to precision radiotherapy targeted at other molecules that are on the surface of other cancer cells,” said Dr. Philip Kantoff, chairman of medicine at Memorial Sloan Kettering Cancer Center in New York.
The investigational treatment, called lutetium-177-PSMA-617, combines a compound that targets a protein on the surface of prostate cancer cells, called prostate-specific membrane antigen, or P.S.M.A., with a radioactive particle that attacks the cells.
The P.S.M.A. protein, which can be detected by imaging scans, is almost exclusively on prostate cancer cells, and so the treatment causes less damage to surrounding tissue, said Dr. Oliver Sartor, the trial’s co-principal investigator and medical director of Tulane Cancer Center in New Orleans.
Though the protein is not ubiquitous in prostate tumors, it is found in more than 80 percent of cases. Among patients screened for the trial, 87 percent were P.S.M.A.-positive. Only those men who were positive for the marker were included in the trial.
The study enrolled men with a form of metastatic prostate cancer called castration-resistant prostate cancer. All the patients had disease that progressed despite treatments with chemotherapy and hormonal therapy to suppress and block androgens.
Participants were randomly assigned to receive the experimental treatment, given every six weeks in up to six doses along with standard treatment, or to continue standard care alone, but without chemotherapy or other isotopes.
After a median follow-up period of 20.9 months, patients given the experimental treatment survived for a median of 15.3 months, compared with 11.3 months for those who received only standard care, a reduction of 38 percent.
Their tumors were more likely to shrink, their prostate-specific antigen levels were more likely to fall, and the risk of their cancer progressing was reduced by 60 percent.
Side effects — most commonly fatigue, dry mouth and nausea — were more prevalent among those receiving the compound than among those who did not, but did not appear to significantly affect quality of life, the researchers said.
The study had some limitations. It was a randomized trial, but because of the difficulties of running a double-blinded trial with a radioactive treatment, the trial was open-label: Both patients and physicians knew whether or not they were getting the treatment. That caused some problems early on, as patients who were disappointed by their assignment withdrew from the trial.
The investigational drug worked where other approaches had failed, Dr. Sartor emphasized. “These patients had received essentially all the available therapies,” he said. “This is the first drug targeted to the tumor that actually results in overall survival benefit among incredibly, heavily pretreated patients.”
Dr. Sartor was a co-principal investigator of the trial, along with Dr. Bernd Krause, of Rostock University Medical Center in Germany. The trial was sponsored by Endocyte Inc. and Advanced Accelerator Applications, which are Novartis companies; Dr. Sartor is a paid consultant to the company. The data were analyzed by the sponsor and provided confidentially to the authors.
Officials with Novartis said the company will apply to the Food and Drug Administration for approval of the new treatment later this year.