PET imaging of bone marrow function by Ga-68-labeled DTPA-mannosyl-dextran

Objectives Our clinical goal is the regional measurement of bone marrow function for radiation therapy planning and whole body imaging for the management of chemotherapy. The objective of this study is to determine if Ga-68-labeled mannosyl-dextran can provide adequate signal and regional pharmacokinetics in the pig model. Tilmanocept (Navidea BioPharm) is a mannosyl-conjugate of dextran (MW=18 kDa) with subnanomolar affinity for CD206, a receptor that resides on the surface of fixed macrophages.

Methods Tilmanocept (15 nmol) was dissolved in 0.2 ml Na acetate (2.0 M) and combined with 2.0 ml of Ga-68 eluate (Eckert & Ziegler). Three adolescent pigs (14 - 15 kg) were imaged; each was positioned with the pelvis and femurs within the field-of-view of a PET/CT scanner (G.E. DVCT). After injection (i.v.) of Ga-68-tilmanocept (12 nmol; 0.8 - 1.1 mCi), a dynamic imaging study (15 min, 0.5 min/fr), was followed by a 5-bed whole body scan (3 min/bed). Time-activity curves (TACs) of the proximal tibia were generated and SUVs were calculated.

Results Radiolabeling was complete (HPLC RCP > 98%) within 15 min and stable for 2 hr. Tibia TACs tibias reached 90% of peak value (0.12 - 0.15 uCi/cc) at ∼3.5 min. The mean SUVs of the 6 tibias, 6 femurs, and 3 lumbar vertebrae were 2.63, 2.29, and 2.04. The SUV of adjacent muscle was 0.34, which yield a marrow-to-muscle ratio of 7.8 and 6.7 for tibia and femur. The average liver and lung SUVs were 13.2 and 1.05.

Conclusions Ga-68-labeled DTPA-mannosyl-dextran provided adequate signal and appropriate pharmacokinetics for functional imaging of bone marrow. A design strategy for a clinical agent will include a chelator with greater gallium stability, and a high MW dextran to eliminate renal filtration.

Research Support NCI In Vivo Cancer and Molecular Imaging Center grant P50 CA12834