Also known as: Lumisight · LUM015
Pegulicianine (Lumisight, LUM015) is a protease-activatable fluorescent imaging peptide used with the Lumicell Direct Visualization System to detect residual breast cancer at surgical margins during lumpectomy. FDA-approved in April 2024, it stays optically "dark" until tumor-associated proteases cleave its peptide linker, unquenching a far-red fluorophore precisely where cancer tissue remains.
Pegulicianine is not a therapeutic drug but an intraoperative imaging agent, built from four covalently linked parts: a Cy5 far-red fluorophore, a QSY21 quencher, a short protease-cleavable peptide linker (reported as Gly-Gly-Arg), and a ~20 kDa PEG chain that increases solubility and lets the agent dwell at tissue surfaces long enough to be useful during surgery.
As administered, the molecule is optically silent — the quencher sits close enough to the fluorophore to suppress its signal. Tumor-associated proteases, particularly cathepsins and matrix metalloproteinases that are overexpressed at the invasive tumor margin, cleave the peptide linker and physically separate the fluorophore from its quencher, producing a bright, localized fluorescent signal specifically where cancer-associated protease activity is present.
The FDA approved pegulicianine (brand name Lumisight) in April 2024, alongside the Lumicell Direct Visualization System, for use during lumpectomy: after the surgeon removes the primary tumor specimen, a handheld imaging probe scans the resection cavity walls in real time, flagging residual cancer tissue that visual inspection alone would miss — potentially avoiding a second surgery to re-excise positive margins.
Approval was supported by the Phase 3 INSITE trial (406 patients), which found pegulicianine-guided imaging identified residual tumor in roughly 7.6% of patients and helped avoid a second surgery in a subset of those with positive margins, alongside earlier first-in-human data published in Science Translational Medicine in 2016.
Pegulicianine's peptide linker is a substrate for cathepsins and matrix metalloproteinases — enzyme classes markedly overexpressed by tumor cells and tumor-associated macrophages, especially at the invasive tumor front. Cleavage of this linker separates the Cy5 fluorophore from its QSY21 quencher, switching the signal from "off" to "on" specifically at sites of elevated tumor-associated protease activity.
The attached ~20 kDa PEG chain slows systemic clearance and increases the molecule's effective size, helping it accumulate and remain at the resection-cavity surface long enough for intraoperative imaging, rather than washing away before the surgeon can scan the tissue.
Administered by IV 2–6 hours before surgery, pegulicianine circulates and is preferentially activated in tumor tissue. During lumpectomy, after removing the primary specimen, the surgeon uses the Lumicell Direct Visualization System — a handheld optical probe — to scan the cavity walls; far-red (Cy5) fluorescence at ~670 nm penetrates tissue well and stands out from background autofluorescence, flagging spots for additional excision in the same operation.
Pegulicianine (Lumisight) is used with the Lumicell Direct Visualization System to detect residual breast cancer at surgical margins during lumpectomy. The most notable safety risk is anaphylaxis (~0.6% of patients across pooled studies) — facilities must have resuscitation equipment available during administration. Chromaturia (blue-green urine) is a common, benign side effect. Contraindicated in patients with a history of hypersensitivity to pegulicianine, including anaphylaxis.
Pegulicianine is a one-time diagnostic imaging agent administered before a specific surgery, not a repeated-dose therapeutic — cycling concepts don't apply. It would only be re-administered ahead of a separate future surgical procedure.
INSITE (Phase 3, NCT03686215): 406 patients enrolled (357 with full image-guided assessment). Residual tumor was identified via pegulicianine-guided margins in about 7.6% of patients (27 of 357); a second surgery was avoided in 9 of 62 patients who had positive margins. Reported sensitivity/specificity figures vary slightly by source (approximately 49% sensitivity, ~85–87% specificity) — treated here as approximate pending direct confirmation against the primary trial publication. A separately cited "84% diagnostic accuracy" figure appears to come from a pooled analysis across five studies and 700+ patients (NEJM Evidence), and should not be conflated with the single-trial sensitivity/specificity numbers above.
Safety: the most notable risk is anaphylaxis, reported in roughly 0.6% of patients across pooled studies (4 of 726); facilities administering pegulicianine are expected to have resuscitation equipment on hand. Chromaturia (blue-green urine discoloration) is a common, benign side effect.
Dosing: 1 mg/kg IV over 3 minutes, administered 2–6 hours before intraoperative imaging.
An earlier first-in-human co-clinical trial (Whitley et al., Science Translational Medicine, 2016) tested LUM015 in 15 patients (12 soft-tissue sarcoma, 3 breast cancer) at 0.5–1.5 mg/kg, and was well tolerated.
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