5ALA

5-ALA, or 5-aminolevulinic acid, is a naturally occurring amino acid that serves as a key precursor in the heme biosynthesis pathway. In humans it is formed in the mitochondria from glycine and succinyl-CoA by ALA synthase and is converted through several steps to protoporphyrin IX, which becomes heme after iron insertion. When exogenous 5-ALA is administered, tissues increasingly accumulate protoporphyrin IX, particularly in malignant or metabolically active cells, due to differences in enzymatic activity and transport.

Because protoporphyrin IX is a photosensitizer, 5-ALA is used in photodynamic therapy to destroy targeted tissue after light activation. Clinically, 5-ALA is employed for dermatologic indications such as actinic keratoses and certain skin cancers, typically with blue or red light. It is also used for fluorescence-guided surgery and tumor detection: administration of 5-ALA or its esterified forms leads to PpIX accumulation that can be visualized under specific illumination, aiding resections of brain tumors and detection of bladder cancer with cystoscopy using hexaminolevulinate.

Safety considerations include photosensitivity lasting roughly 24 to 72 hours after administration, requiring avoidance of bright light. Common adverse effects include headache, nausea, vomiting, or local skin irritation. Use is guided by regional approvals and contraindications, and pregnancy should be discussed with a clinician.

Regulatory status varies by country. Marketed derivatives include Gliolan (5-ALA) for brain tumor surgery and hexaminolevulinate-based solutions for bladder cancer detection. Ongoing research explores broader imaging applications and combination therapies.