Feasibility of [99mTc]Tc-Mannosylated Human Serum Albumin for Lymphoscintigraphy: A Phase 1/2 Clinical Trial

Abstract Purpose Lymphoscintigraphy is crucial for diagnosis of lymphatic abnormality and sentinel lymph node (SLN) detection in surgery. We investigated the feasibility of [ 99m Tc]Tc-mannosylated human serum albumin (MSA) as a new imaging agent for lymphoscintigraphy. Methods In the first part, three healthy volunteers were enrolled to evaluate the safety and basic efficacy of [ 99m Tc]Tc-MSA, using [ 99m Tc]Tc-phytate as a comparator. In the volunteers, the two radiopharmaceuticals were injected into the interphalangeal web of bilateral feet on different days. Whole-body scans were performed serially until 24 h after the injection. The biodistribution, radiation dosimetry, and safety were evaluated. In the second step, six breast cancer patients planned for operation were enrolled. SLN imaging was performed using [ 99m Tc]Tc-MSA two days before operation, and again on the day of operation using [ 99m Tc]Tc-phytate. The efficacy of SLN detection was evaluated using a visual grade system and compared between the two different radiopharmaceuticals. Results [ 99m Tc]Tc-MSA and [ 99m Tc]Tc-phytate show comparable biodistribution in evaluated organs and inguinal lymph node stations. [ 99m Tc]Tc-MSA showed relatively slower migration speed through lymphatic vessels and clearer visualization of lymphatics than [ 99m Tc]Tc-phytate. No abnormality was observed in safety parameters. In the radiation dosimetry, whole body dose at usual injection dose (74 MBq) was estimated to be 236 µSv. In SLN imaging in breast cancer patients, [ 99m Tc]Tc-MSA showed higher target-to-background ratio than [ 99m Tc]Tc-phytate, with clear visualization of SLN with both imaging agents. Conclusion [ 99m Tc]Tc-MSA is a safe and effective imaging agent for lymphoscintigraphy. Particularly, [ 99m Tc]Tc-MSA can be a more effective radiopharmaceutical for SLN imaging than [ 99m Tc]Tc-phytate.