%0 Journal Article %A Nina Eberhardt %A Jessica Loeffler %A Marco Raabe %A Hao Li %A Alireza Abaei %A Hendrik Herrmann %A Christoph Solbach %A Tanja Weil %A Ambros Beer %A Volker Rasche %A Gordon Winter %T Biodistribution studies of 89Zr-labeled nanodiamonds in mice using PET and MRI %D 2020 %J Journal of Nuclear Medicine %P 1085-1085 %V 61 %N supplement 1 %X 1085Objectives: Nanodiamonds (NDs) are of paramount interest for medical applications as chemically-inert particles due to their biocompatibility [1]. NDs with nitrogen vacancies (NV centers) further have the potential for sensitive MRI after hyperpolarization. For assessment of the long-term biodistribution of the NDs, additional labeling by radiotracers appears promising. The objective of this study was to combine PET imaging and high-resolution anatomic MRI for sensitive assessment of the longitudinal ND biodistribution with accurate anatomical localization. As NDs cannot be directly radio-labeled, a PEGylated HSA (human serum albumin) protein coating, additionally functionalized with desferal for radiotracer binding, was applied. First studies of 68Ga- and 89Zr-labeled NDs in mice were performed. Methods: Fluorescent NDs (Ø 100 nm, Microdiamant, IOM Leipzig, Germany) surface coated by HSA with the chelator p-SCN-Bn-deferoxamine (Macrocyclics, USA) and PEG-2000 groups were radioactively labeled using zirconium-89 or gallium-68. For biodistribution and tumor accumulation studies a CB17/Icr-Prkdc scid/Crl (Charles River) mouse model was used. Tumor xenografts were established in the subscapular region of the SCID mice using 1 x 106 cells of the prostate carcinoma cell lines LNCaP C4-2 and PC-3. In a subgroup, additional anatomic MR imaging was performed at 11.7 T (BioSpec 117/16, Bruker Biospin, Ettlingen, Germany). For PET imaging, 42.4 ± 4.4 µg of radio-labeled NDs were injected intravenously. Dynamic 60-min duration PET scans (Focus 120, Concorde Microsystems Inc.) were performed directly after injection (0 h), and 1 h and 3 h (68Ga-labeled), or 3 h, 24 h, 3 days and 7 days (89Zr-labeled) post injection. Excised organs were measured in the gamma counter (Cobra II, Perkin Elmer, Waltham, USA) for accurate quantification of the accumulated dose at each time point (n = 4). Images were reconstructed using an OSEM3D/MAP algorithm with 2 OSEM3D iterations and 18 MAP iterations. Cross modal PET-MRI image fusion and data analysis was performed with Slicer3D and AsiPro. Results: The 89Zr-labeling for NDs was stable in sodium chloride (0.9 %), cell culture medium and serum during a 4-day observation period. By superposition of PET and MR images an increase of activity in the first 60 min was observed in liver and spleen, while in the heart region the activity signal decreased. After 1 h, 3 h, 24 h, 3 days and 7 days of incubation in the mouse model accumulation was observed only in liver and spleen. Marginal accumulation was observed in both tumorxenografts. There was a slight increase of activity detected in LNCaP C4-2 tumors starting at (0.4 ± 0.3) %ID up to (1.5 ± 0.6) %ID after 3 days followed by a decrease of the signal to (0.9 ± 0.6) %ID after 7 days. In PC-3 there was a short peak in the first measurement of (0.6 ± 0.4) %ID followed by a constant accumulation level of (0.2 ± 0.1) %ID. From 0 h to 7 days incubation time the activity in the blood decreased from (5.2 ± 2.0) %ID to (0.02 ± 0.01) %ID, whereas in the liver there is a fast increase (40.4 ± 17.7) %ID to (66.9 ± 3.4) %ID after 1 h and a slow decrease over time to (49.5 ± 8.6) %ID after 7 days. In the spleen an increase starting from 0 h (2.1 ± 0.5) %ID to 24 h with (6.0 ± 1.4) %ID followed by a slight decrease at 7 days (3.4 ± 0.9) %ID was observed. Conclusions: NDs with specific protein coating were successfully radioactively labeled and analyzed regarding biodistribution and accumulation for the first time in mice. Accumulation was observed mainly in organs of the reticuloendothelial system. These data are used as a base for the further optimization of the surface modifications to improve the pharmacokinetic and pharmacodynamic properties of the protein-coated NDs. References: [1] Zhu Y, Li J, Li W, et al. The biocompatibility of nanodiamonds and their application in drug delivery systems. Theranostics. 2012;2(3):302-312. %U