Amidst the “burgeoning” interest in developing novel optical imaging drugs and imaging devices to assist various standard surgical procedures, the US Food and Drug Administration (FDA) recently issued guidance regarding clinical trial design features supporting the development and approval of optical imaging agents. According to the agency, a contributing factor propelling the advancement of these drugs is the use of minimally invasive surgical procedures, which are associated with a loss of tactile perception and a more narrowed field of view.
As explained in the FDA’s new draft guidance for industry Developing Drugs for Optical Imaging published in January 2025, optical imaging is the use of light in conjunction with imaging drugs and devices during medical procedures to assist in the detection of tumours or other pathology and delineation of normal anatomical structures. Surgeons employ these drug/device pairings to help with the direct visual inspection and palpation of tissue in the surgical field. Because imaging drugs enhance the surgeon’s ability to discern tumours from normal tissue, they can augment the likelihood of safe and complete removal of cancers and minimise the risk of unintended injury to the normal structures.
Optical imaging is advantageous as an imaging modality because it significantly reduces patient exposure to harmful radiation by using non-ionising radiation, which includes visible, ultraviolet, and infrared light, the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (NIH), explains. Since it is much safer than techniques that require ionising radiation such as X-rays, optical imaging can be used for repeated procedures to monitor disease progression or the results of treatment.
The new guidance focuses on the use of optical imaging for tumour detection (surgery, endoscopic resection of neoplasm), lymph node staging (lymphatic mapping, Sentinel lymph node identification), and the enhanced delineation of normal anatomy to decrease risk of injury (e.g., nerve structures in head and neck surgery). The FDA notes that optical imaging drugs are generally governed by the same regulations as other drugs.
Moreover, its recommendations to developers of other medical imaging drugs – published in three separate guidance documents more than 20 years ago– remain applicable to optical imaging drugs.
Strengthening Surgical Success
In 2024, the FDA approved 50 “novel” drugs, either as new molecular entities (NMEs) under new drug applications (NDAs) or as new therapeutic biologics under biologics license applications (BLAs), as summarised in the agency’s 14th annual report, Advancing Health Through Innovation: New Drug Therapy Approvals 2024 issued in January 2025. In novel drugs, the active ingredients have not been previously approved in the US. Patrizia Cavazzoni, MD, then directorof the Center for Drug Evaluation and Research (CDER), FDA, stated in the report that it features “notable” drug approvals that CDER considers “likely to have a significant impact on patient care and public health.”
Among the 50 agents, CDER highlighted the optical imaging prodrug pegulicianine as one of the notable first-in-class approvals. Granted marketing authorisation under the trade name Lumisight from Lumicell, Inc, pegulicianine is optically inactive when intact but produces a fluorescent signal after its peptide chain is cleaved by cathepsins and matrix metalloproteases. The levels of these enzymes are higher in and around tumour and tumour-associated cells than normal cells. This enzymatic cleavage generates two optically active metabolites that fluoresce and another fragment that contains the fluorescence quencher that maintains the intact molecule optically inactive.
Pegulicianine is administered as an intravenous injection for fluorescence imaging in adults with breast cancer as an adjunct for the intraoperative detection of cancerous tissue within the resection cavity following removal of the primary specimen during lumpectomy surgery. It was approved for use with the Lumicell Direct Visualisation System (DVS) or another fluorescence imaging device that is FDA approved for use with pegulicianine in the indicated population.
