Healthcare (Commonwealth Union) – Cancerous cells have a significantly higher metabolic rate than normal cells, leading them to consume greater amounts of glucose. This trait is leveraged by Positron Emission Tomography (PET)—currently the top-tier imaging method for cancer diagnostics. In PET scans, doctors inject a radioactive glucose-based tracer such as 18F-fluoro-2-deoxyglucose (18F-FDG), which gathers at tumour sites, making them easier to locate. However, PET scans come with a high price tag and involve radiation exposure, which can build up with repeated use. As cancer cells consume much higher quantities of glucose in comparison to normal cells a PET scan gives the ability to distinguish cancer cells in comparison to healthy cells and diagnose cancer.
Now, scientists at the Department of Bioengineering, Indian Institute of Science (IISc) have introduced a new biocompatible small molecule that serves as a minimally invasive contrast agent for Photoacoustic (PA) Tomography. This imaging approach involves directing a near-infrared (NIR) laser at specific light-absorbing molecules (chromophores) delivered to the target area. These molecules absorb the light and expand, causing a change in pressure that produces an audible signal. By decoding these signals, researchers can generate 3D visuals of the area being examined. The method is especially effective for detecting tumours near the body’s surface.
“This method allows us to gather the same diagnostic insights using a much more affordable technique—less expensive than both PET and MRI,” said Sanhita Sinharay, who is Assistant Professor in Bioengineering and the lead author of the study, which was recently seen in JACS Au.
At present, clinical photoacoustic imaging relies solely on naturally occurring pigments such as haemoglobin, which are inherent to the human body. The oxygenated and deoxygenated forms of haemoglobin exhibit distinct optoacoustic patterns, serving as valuable indicators of abnormal metabolic activity.
In a recent study, researchers at IISc developed a synthetic molecule—absent in typical human cells—to enhance sensitivity and image contrast. This improvement allows for clearer distinction between diseased and healthy tissue. The molecule, named GPc, is composed of four glucose molecules attached to a zinc-phthalocyanine-based core.
Phthalocyanines are compounds that, upon excitation in the near-infrared (NIR) range, primarily release energy through nonradiative means, making them ideal for photoacoustic applications. When designing GPc, the scientists anticipated that incorporating four glucose molecules would facilitate better cellular absorption. These glucose units, each containing hydrophilic hydroxyl groups, also contributed to greater water solubility of the compound.
Pooja Patkulkar, a PhD researcher at the Department of Bioengineering and the study’s lead author pointed out that a key breakthrough for them was investigating how the probe functions using the Seahorse assay.
She further indicated that their goal was to determine whether the designed molecule was being absorbed via glucose transporters and to track what happens to it once inside the cell, so they aimed to compare its activity to that of 18F-FDG to find out if it acts like glucose or blocks glucose activity.
A compound that acts as a glucose agonist would compete with glucose for uptake and be broken down by the cell, making it unsuitable as a contrast agent. To clarify the nature of the newly developed agent, the researchers conducted a competitive assay comparing GPc and glucose. They discovered that GPc could readily enter human cells, was not metabolised, and did not rely on the GLUT1 transporters typically responsible for glucose absorption. Nonetheless, the researchers emphasized the need for further investigation to fully understand GPc’s role after it enters cells.
Sinharay indicated that one of the strengths of their study was showing, at least in part, how the probe behaves inside cells and confirming that it reaches the tumour core, which is often marked by low oxygen levels.
