Evidence Grade A — Regulatory approved. 5 published studies. 3 registered clinical trials.
Medically reviewed by a licensed medical professional
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Pegulicianine (sold as Lumisight) is an imaging agent injected before breast cancer lumpectomy surgery that makes residual cancer tissue glow under a special camera. It is the first fluorescence imaging agent designed specifically for breast cancer surgery. By helping surgeons see and remove cancer that might otherwise be left behind, it can reduce the need for a second operation — which currently happens in about 1 in 5 lumpectomy patients.
Pegulicianine is also known by these brand and alternate names:
5 published studies: 3 human, 0 animal, 0 in-vitro, 1 reviews
Pegulicianine is marketed as Lumisight (approved January 2025) as an adjunct for detection of residual cancer during breast-conserving surgery (lumpectomy). It is given as an intravenous infusion 2–6 hours before surgery.
In the INSITE trial, the rate of positive surgical margins (cancer left at the edge of removed tissue) was reduced from 9.6% to 3.6% when surgeons used pegulicianine fluorescence guidance. Positive margins typically require a second surgery, so reducing them has direct clinical impact. The technology represents a new approach to surgical oncology — using the tumour's own metabolic characteristics to make it visible in real time during the operation.
Cancer cells have abnormal metabolism that makes their surrounding environment more acidic than normal tissue (pH 6.2–6.8 versus 7.4). Pegulicianine exploits this difference: at normal body pH, the fluorescent dye component is chemically silenced. When it encounters the acidic environment around tumour tissue, the dye undergoes a chemical change that switches on its near-infrared fluorescence. Surgeons using a specialised camera can then see the cancer tissue glowing, guiding them to remove residual disease that is invisible to the naked eye.
In the Phase III INSITE trial, pegulicianine-guided surgery reduced the rate of cancer left at surgical margins from 17% to about 15% — with 9 patients who would have needed a second surgery being spared that procedure. The specificity (ability to correctly identify non-cancerous tissue) was 85%, though sensitivity (ability to detect all cancer) was moderate at 49%. Overall, the system improved outcomes in about 10% of patients treated. The technology exploits a fundamental difference between cancer and normal tissue: the acidic environment around tumour cells activates the fluorescent dye, while it remains dark in healthy tissue. Serious allergic reactions including anaphylaxis occurred in 0.6% of patients. The manufacturer is exploring use in other solid tumours including head and neck cancers and sarcoma.
PeptideTrace tracks 3 registered clinical trials for Pegulicianine sourced from ClinicalTrials.gov.
Post-market Evaluation of LumiSystem: Intraoperative Margin Performance and Clinical Utility (IMPACT) Registry
Study to Image Inflammatory Activity of a Fluorescence Imaging Agent in Excised Human Artery Plaques
The Impact of Surgeon-Interpreted Intraoperative Margin Assessment During Breast Conserving Surgery on Postoperative Treatment
FDA ORIG 1
Pegulicianine is a PEGylated fluorescent imaging agent: pH-activatable cyanine dye conjugated to PEG polymer. MW ~35 kDa. Fluoresces NIR (~800 nm) only in acidic tumor microenvironment (pH <6.5), quenched at physiological pH. PEG extends half-life via EPR effect for tumor accumulation. Single IV 1 mg/kg infusion 2-6 hours before surgery.
Exploits Warburg effect: tumor aerobic glycolysis creates acidic extracellular pH (6.2-6.8 vs. 7.4). At physiological pH, cyanine dye is aggregated and non-fluorescent. Acidic pH causes protonation, conformational change, and fluorescence activation. PEG enhances tumor accumulation via EPR. Under NIR imaging during surgery, residual tumor fluoresces for real-time margin visualization.
Marketed as Lumisight. Approved January 9, 2025. INSITE (Phase III; N=406): positive margin rate reduced from 9.6% to 3.6% (P=0.042). Detection sensitivity 49.3%. Specificity 86.8%. Indication: adjunct for residual cancer detection during breast cancer lumpectomy. First FDA-approved fluorescence agent for breast cancer.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Palopegteriparatide is marketed as Yorvipath (Ascendis Pharma, approved August 2024). It is the first FDA-approved PTH replacement therapy for hypoparathyroidism, a condition that previously had no approved hormone replacement and was managed only with high doses of calcium supplements and active vitamin D — an approach that does not fully normalise calcium metabolism. In the PaTHway trial, 79% of patients achieved independence from calcium and active vitamin D supplements while maintaining normal blood calcium levels, compared to 5% on placebo. This represents a fundamental shift in managing hypoparathyroidism — from supplementation to actual hormone replacement. Patients also showed improvements in kidney function markers and bone metabolism parameters.
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