Conceptual image for viral ethiology of prostate cancer

A first-in-man study, by researchers at the Nuffield department of surgical sciences and the department of oncology, at the University of Oxford, Oxford University Hospitals and Oxford NIHR Biomedical Research Center University of Oxford, and at Oxford University Hospitals NHS Trust, demonstrates how a fluorescent marker dye that sticks to prostate cancer (PC) cells acts like a “second pair of eyes” during surgery, helping surgeons to visualize and remove cancer cells that might otherwise be missed, while preserving healthy tissue.

The study is published in the European Journal of Nuclear Medicine and Molecular Imaging.

The approach uses a humanized prostate-specific membrane antigen (PSMA)-targeting antibody fragment minibody, IAB2M, attached to a near infrared (NIR) dye, IRDye800CW-NHS ester, to generate the construct IR800-IAB2M. The cancer cell-targeting dye was first tested in preclinical models, and then evaluated in 23 men with prostate cancer, who were injected with the marker dye to help surgeons visualize prostate cancer cells during subsequent robot-assisted laparoscopic radical prostatectomy (RARP), using fluorescence molecular imaging (FMI). The marker dye found areas of cancerous tissue not picked up by the naked eye or other clinical methods, and allowed the surgeons to remove all cancerous tissues. This ability could reduce the chances of cancer coming back, whilst preserving healthy tissues.

Freddie Hamdy, PhD, Nuffield Professor of Surgery at the University of Oxford explained, “We are giving the surgeon a second pair of eyes to see where the cancer cells are and if they have spread.  It’s the first time we’ve managed to see such fine details of prostate cancer in real-time during surgery. With this technique, we can strip all the cancer away, including the cells that have spread from the tumor which could give it the chance to come back later. It also allows us to preserve as much of the healthy structures around the prostate as we can, to reduce unnecessary life-changing side-effects like incontinence and erectile dysfunction.”

The IR800-IAB2M molecule combination was developed by Oxford scientists in collaboration with ImaginAb. The tracer was considered safe for clinical applications as the minibody had already been used in the clinic, and the fluorophore has been used in numerous clinical applications.

The tracer’s use effectively allows surgeons to see the edges of the tumor and identify any clusters of cells that have spread from the tumor into nearby pelvic tissues and lymph nodes. This guides the surgeon to remove all cancerous tissues and preserve healthy areas around the prostate. This ability substantially reduces the chances that the cancer will come back in future but also minimizes the possibility of life changing side-effects for the patient after the operation.

In the first stage of the Prostate MOlecular Targeting to Enhance surgery (ProMOTE) study, 23 men diagnosed with prostate cancer were injected with the fluorescent dye before undergoing robot-assisted radical prostatectomy). Surgeons used an imaging system that shines a special type of light on the prostate and nearby areas, to make the prostate cancer cells glow. The imaging system was developed by an engineering team led by Borivoj Vojnovic, PhD, at the University of Oxford.

While the trial included 23 patients, the published report presents detailed results from six cases as exemplars. For multiple patients in the study, the dye identified clusters of cells which had spread away from the tumor which couldn’t be seen by the naked eye. “Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity,” the investigators reported. There were no side-effects associated with the administration of the tracer.

This marker dye is in its early stages of clinical development, but in future it could be used routinely by surgeons to see every part of the cancer while they perform surgery to remove the prostate. The imaging system to see glowing cancer cells could be integrated into the robot-assisted tools used for prostate surgery. The marker dye could also be used for other types of cancer, by changing the protein it uses to attach itself to the cancer cells.

Further clinical trials are already underway in larger groups of patients to find out if the technique removes more prostate cancer, and preserves more healthy pelvic tissue, compared to existing surgical methods. “Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP,” the team wrote. “Findings from our study and others should pave the way for a systematic and simultaneous evaluation of multiple molecularly targeted agents using the most cutting-edge fluorescence platforms integrated in robot-assisted surgical equipment, in order to reach consensus and change future practice based on robust evidence,” the authors wrote in their paper.

“Prostate surgery is life changing,” Hamdy said. “We want patients to leave the operating theatre knowing that we have done everything possible to eradicate their cancer and give them the best quality of life afterwards. I believe this technique makes that possibility a reality.”

Executive director of research and innovation at Cancer Research UK, Iain Foulkes, PhD, said, “Surgery can effectively cure cancers when they are removed at an early stage. But, in those early stages, it’s near impossible to tell by eye which cancers have spread locally and which have not. We need better tools to spot cancers which have started to spread further. The combined marker dye and imaging system that this research has developed could fundamentally transform how we treat prostate cancer in the future. We hope that this new technique continues to show promise in future trials. It is exciting that we could soon have access to surgical tools which could reliably eradicate prostate and other cancers and give people longer, healthier lives free from the disease.”

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