Excellent video! After watching quite a few videos, your opening music was a breath of fresh air, and your explanations of difficult concepts was creative and informative. (I also really enjoy your poster design).
Two questions, has your team begun testing on mice or small animals? If so, what kind of success have you seen with your drug delivery method?
Thank you for your very kind comments, we’re glad you enjoyed our presentation!
Right now, the 188Re-N2S2 and 188Re-N3S complexes have not progressed to the point where we can attempt mouse studies. We’re still developing the chemistry that will allow us to attach our complexes to our antibody.
We are, though, very excited about the possibilities, and eager to move this project forward to the point where we can test in vivo.
Thanks again for your feedback, and let us know if you have more questions.
Margery,
As Sam said, Thank you for the kind comments.
In addition to the N2S2 and N3S work moving closer to in vivo testing, we are planning to test the effective specific activity of our accelerator-produced 186Re product in vivo soon and compare the achievable specific activity to the specific activity of generator-produced 188Re.
Thanks and please let us know if you have more questions.
All the best,
Matt
Stellar video guys!
Thank you!
Further posting is closed as the event has ended.
Marc Porter
Faculty: Project PI
How will the Re-ligand complex by linked with the targeting antibody? Do you have an example in mind as to the first cancer to go after as a model?
Sam Groveman
Thanks for the question!
We have been exploring various means to attach the bifunctional chelate to an antibody, including active esters, thiolactones, and even a tetrazine method. We first need to determine the best ligand core before testing the various linkers, so we can’t say which linker would be best yet.
As for the cancer, the 6D2 antibody developed at our partner institution Albert Einstein School of Medicine would be well suited to 188Re, and targets melanoma, so that would likely be our first target.
Jon Kellar
Faculty: Project Co-PI
What is the toxicity of Rhenium 186 and 188 to humans?
Matthew Gott
Graduate Student
Hello Jon,
Thank you for the question.
With Re-186 and Re-188, the toxicity is going to be more associated with the radiation dose than the metal toxicity. We only need to use trace level quantities of rhenium to induce the desired effect.
As an example from a published study, Re-188 was used to treat metastatic bone pain. Each patient received 75-96 nanograms of Re-188.
Please let us know if you have further questions.
All the best,
Matt
Adriane Ludwick
Faculty: Project Co-PI
What rhenium complexes have been sythesized thus far? Or is there a particular complex synthesis underway? Please give more details on this part of the project.
Sam Groveman
Thanks for the question!
Currently, we have synthesized Re-complexes for all of the ligands described in the poster, i.e. Re-P11, Re-BAT-TECH, Re-FGC, and Re-FKC. While we have synthesized the complexes, we are still investigating the complex stabilities to determine the best ligand.
We are also adding linker groups to our ligands to develop the bifunctional chelate, this will necessitate a reevaluation of the stabilities of the ligands, so those syntheses are still underway.
Please let us know if you have further questions.
Peter Gannett
Faculty: Project Co-PI
The use of antibodies for targeting can be a very effective approach. However, they sometimes induce an immune response themselves. Has 6D2 shown any tendency to do this and do you think attachment of the Re complex will alter this?
Sam Groveman
Hi Peter, thanks for the question!
Phase I clinical trials of directly labeled 6D2 didn’t show any immune response, however, the trials were only for lethal metastatic melanoma and a small sample size of patients. While the results are encouraging, further investigation is needed before we can draw conclusions about immune response.
The 6D2 in the trial had 188Re directly labeled into the antibody, so using a bifunctional chelate would likely change the structure of the antibody even less than the direct labeling. While we can’t say for sure without further trials, there would likely be no increased chance of immune response from the addition of Re.
I hope that helps, and please let us know if you have any further questions.
Antal Jakli
Faculty: Project Co-PI
How does the half-life of 186RE relate to the localized dose to tumors?
Matthew Gott
Graduate Student
Thank you for the great question.
The ~90 hr half-life allows time for slower metabolizing biomolecules such as antibodies to circulate and localize at the tumor site. With the longer half-life, there will be less damage to healthy tissues as the radiopharmaceuticals circulate through the body compared to a short-lived isotope.
With its shorter half life (17 hr), Re-188 is better suited for faster circulating antibodies and peptides.
Please let us know if you have any further questions.
All the best,
Matt