Blue light cystoscopy
Friday 10 December 2010
Recent research into cancer detection and treatment provides an interesting example of how connections can be made between various parts of the IB syllabus. Specifically porphyrins in hemoglobin (B.9.2), UV-VIS spectroscopy (A.8.4), enzymes (B.7.1), drug design (D.8.4), functional groups (10.9.1), esterification (20.4.1) and acid-bases (8.3.2) – to name just a few!
Protoporphyrin IX (PpIX) (left) is a porphyrin derivative that combines with Fe2+ ions to form the heme of hemoglobin, i.e. it is an intermediate in the biosynthesis of heme. It fluoresces in the red region of the spectrum with λmax of 621 nm. Mutant cancer cells, which proliferate excessively, accumulate substantially more PpIX than normal cells.
Part of the biosynthesis of PpIX involves the formation of 5-aminolevenulic acid which is catalysed by the enzyme 5-aminolevulinic acid synthase. If extraneous 5-aminolevulinic acid is added to cancerous cells it induces the biosynthesis of an excess of Pp IX. Shining blue light onto the cells photoactivates the PpIX which then fluoresces with its characteristic red light. Hence cancer cells show up in the blue light which aids in their early detection.
The effect of the aminolevulinic acid (right) is enhanced even further if it is delivered in the form of an ester (with a relatively long carbon chain) as this makes it more lipophilic which means it remains in the cancer cells longer. The ester (hexyl aminolevulinate) is delivered in the form of its hydrochloride salt, shown below, (causing protonation of the –NH2 group) to increase its solubility in water before the ion reverts back to its molecular form once inside the cell.
In the video below consultant urological surgeon Rhidian Hurle working at the Princess of Wales Hospital in Bridgend, Wales, UK shows how he is using this technique for the early detection of bladder cancer.