Ga-68- and Cu-64-Labeled NOTA-Albumin Conjugates for PET Sentinel Lymph Node Imaging

Our objective was to develop and evaluate Ga-68- and Cu-64-labeled albumin conjugates for PET imaging of sentinel lymph nodes. Four different albumin conjugates were prepared starting from NOTA-HSA. The lymph node uptake of Ga-68- and Cu-64-labeled albumin conjugates was investigated after subcutaneous injection into the foot pad of Wistar rats. A pig model was utilized for further biological evaluation of the lymph node uptake. For all the four conjugates, radiolabeling with Ga-68 and Cu-64 resulted in >95% radiochemical yield. Denatured and mannosylated Ga-68 NOTA-HSA revealed the highest popliteal lymph node uptake in rats ( % ID and % ID 10 min and 60 min p.i., resp.). The popliteal lymph node reached its maximum activity after approximately 120 min and remained constant for denatured and mannosylated Cu-64 NOTA-HSA at least up to 240？min p.i. In a pig model, 2% of the injected dose of this compound was found in the sentinel lymph node 60 min after subcutaneous injection. In conclusion, PET imaging of sentinel lymph nodes with Ga-68- and Cu-64-labeled denatured NOTA-Man-HSA could be successfully demonstrated and deserves further investigations. 1. Introduction Sentinel lymph node (SLN) diagnosis is an important field in nuclear medicine, and its benefit has been proven in many cancer types, mainly breast cancer and melanoma. The sentinel lymph node is the first lymph node in the drainage basin of a primary tumor. SLN detection is a two-step procedure. In the first step, SLNs are imaged by means of planar lymphoscintigraphy. Recently, the advantage of SPECT/CT in cases with difficult anatomical location of sentinel nodes was reported as an alternative imaging modality [1, 2]. In the second step of the procedure, SLNs are intraoperatively detected by a hand-held gamma camera, excised and pathologically examined. If the sentinel node is free of metastatic cells, the likelihood of general nodal metastasis is very low. In general, technetium-99m-labeled colloids in combination with blue dyes are used to detect the sentinel lymph node. The labeled colloids are injected beneath the skin surrounding the primary tumor or alternatively directly into the tumor. After entering the lymphatic vessels, colloids use the same drainage pathway as potential metastatic cancer cells and are eventually retained in the first draining lymph node (sentinel node) by phagocytosis or mechanical trapping. In Europe, mainly the colloids based on denatured human serum albumin are used, whereas in USA; sulphur colloid is preferred. There are two crucial factors in the performance