Researchers test an integrated molecular imaging procedure at a scale closer to the human body
Detecting very small bladder cancer lesions, including tissue that may remain after surgery, can be challenging. PHIRE international research team composed of Ospedale San Raffaele (IT), Ascend Technologies (UK), Fujifilm Visualsonics (NL), University of Bologna (IT) and META Group (BE) has reached an important preclinical milestone, testing its complete imaging procedure in a pig model whose anatomy more closely resembles that of humans than smaller animal models.
The study provides information about whether the different parts of the technology can work together in a more realistic setting. It helps the team to understand what must be addressed before clinical investigation can be considered.
From individual technologies to an integrated procedure
PHIRE developed molecular photoacoustic imaging for bladder cancer. The approach combines imaging with molecular information, with the longer-term aim of helping clinicians identify tissue characteristics that may not be apparent through conventional visualisation alone. This could be relevant when looking for very small lesions or residual tumour tissue after resection.
The technologies behind PHIRE have previously been studied in laboratory settings and small-animal models. The latest test focused on the complete procedure: whether its components could be brought together safely and feasibly at a larger anatomical scale, and what technical limitations might emerge in a living system.
“The broader challenge for PHIRE was no longer simply demonstrating that its individual components work, but demonstrating that the integration of all components is safe and feasible”
– Dr Massimo Alfano, project coordinator of PHIRE and research group leader at Ospedale San Raffaele of Milan
Pigs were chosen because their body size and anatomy, including the dimensions of the bladder and abdominal wall, allow the procedure to be reproduced more realistically than in smaller animals. The test examined safety, reproducibility and feasibility, while also helping the researchers identify issues that may not be apparent in simplified laboratory conditions.
As the team’s experience illustrates, results from laboratory experiments do not always translate directly to a living system. Testing the full workflow helps reveal which variables need to be controlled, adapted or investigated further.
“Performance measured in simplified laboratory conditions does not translate directly to a living large-animal system”
– Dr Massimo Alfano, project coordinator of PHIRE and research group leader at Ospedale San Raffaele of Milan
Why large-animal testing matters
A large-animal study can address questions that cannot be fully answered using cell cultures, tissue phantoms or smaller animals. It provides an intermediate step between proof-of-concept research and potential future clinical investigation, allowing the integrated procedure to be assessed at a scale closer to that of human patients.
Animal welfare was considered throughout the experimental design. The study followed the principles of the 3Rs (Replacement, Reduction and Refinement) and the approved animal-study protocol. Trained personnel and veterinary professionals oversaw the animals, with anaesthesia and physiological monitoring during the procedure. Large-animal testing is used only when the relevant questions cannot be adequately answered through alternative methods.
“Animal welfare is a fundamental part of the experimental design rather than an additional consideration”
– Dr Massimo Alfano, project coordinator of PHIRE and research group leader at Ospedale San Raffaele of Milan
What comes next?
The findings will help the PHIRE team refine the system, define specifications for the next generation of the technology and address technical risks identified during testing. Further development and preclinical evidence will be needed before the approach can move towards clinical investigation and any potential use in patients.
In the longer term, PHIRE aims to give urologists additional molecular information during bladder cancer procedures. If the technology can be successfully translated into clinical practice, it could complement conventional visualisation and potentially help clinicians identify small or residual lesions that are difficult to detect with current techniques.
“Our goal is to give urologists a new way of identifying disease — not only by what the eye can see, but also by the molecular characteristics of the tissue”
– Dr Massimo Alfano, project coordinator of PHIRE and research group leader at Ospedale San Raffaele of Milan
By testing the complete procedure in a setting closer to the human body, PHIRE is contributing to defining the evidence and technical refinements still needed on the path towards clinical translation for bladder cancer early-detection.
