Identifying sentinel nodes near the primary tumor remains a problem in, for example, head and neck cancer because of the limited resolution of current lymphoscintigraphic imaging when using 99m Tc-nanocolloidal albumin. This study describes the development and evaluation of a nanocolloidal albumin-based tracer specifically dedicated for high-resolution PET detection. Methods: 89 Zr was coupled to nanocolloidal albumin via the bifunctional chelate p-isothiocyanatobenzyldesferrioxamine B. Quality control tests, including particle size measurements, and in vivo biodistribution and imaging experiments in a rabbit lymphogenic metastasis model were performed. Results: Coupling of 89 Zr to nanocolloidal albumin appeared to be efficient, resulting in a stable product with a radiochemical purity greater than 95%, without affecting the particle size. PET showed distinguished uptake of 89 Zr-nanocolloidal albumin in the sentinel nodes, with visualization of lymphatic vessels, and with a biodistribution comparable to 99m Tc-nanocolloidal albumin. Conclusion: 89 Zr-nanocolloidal albumin is a promising tracer for sentinel node detection by PET.Key Words: sentinel node; PET/CT; 89 Zr; Nanocoll; head and neck cancer Thesent inel node (SN) procedure is applied in a variety of tumor types, including head and neck squamous cell carcinoma (HNSCC) (1,2). Although, in general, results in HNSCC are good, adequate detection of the SN in floor-ofmouth tumors, compared with other sites, appeared problematic, as illustrated by significantly lower sensitivity and negative predictive value (1). This is probably due to the short distance between the primary tumor and the first draining lymph nodes (SNs) in combination with the limited resolution of planar lymphoscintigraphy and SPECT. The injection site (around the primary tumor) produces a large focus of intense activity on planar lymphoscintigraphy, possibly hiding SNs near the primary tumor. As a result, second-echelon lymph nodes may erroneously be considered SNs; this is also true for SPECT: the added value of detecting foci hidden at planar scintigraphy may be offset by its lack of dynamic information with the typically fast kinetics of lymph drainage in HNSCC.PET provides dynamic 3-dimensional information at a higher spatial resolution than achievable with a g-camera.Theoretically, these characteristics may better differentiate between the first-and second-echelon nodes. To the best of our knowledge, no PET radiocolloids specifically dedicated to lymphatic mapping are clinically available yet. The aim of this study was to develop and evaluate in a rabbit lymphogenic metastasis model a 89 Zr (half-life, 78 h)-nanocolloidal albumin (Nanocoll; GE Healthcare)-based PET radiocolloid dedicated to SN detection. Results were compared with 99m Tc-nanocolloidal albumin ( 99m Tc half-life, 6 h).
MATERIALS AND METHODSPreparation of 89 Zr-and 99m Tc-Nanocolloidal Albumin A 0.5-mg kit for the labeling of colloidal human serum albumin with 99m Tc was premodified with p-isothiocyanatobenzyldesferriox...