Comparison of carrier-added [99mTc] EDTMP and carrier-free preparations of [99mTc] EDTMP and [99mTc] DPD

Full text: High uptake of bone-seeking radiopharmaceuticals in malignant bone lesions is a prerequisite for adequate bone scanning. Visual image analysis is impaired due to high soft-tissue activity with currently available [99mTc]-EDTMP-kits. This study aimed to compare carrier-added [99mTc]-EDTMP with carrier-free [99mTc]-EDTMP and [99mTc]-DPD preparations in clinical routine. 15 μg and 150 μg perrhenic acid respectively were added to [99mTc]-pertechnetate (>6 GBq in 3 ml phys. saline). The solution was then transferred into a vial, containing 1 mg of EDTMP, 3.6 mg stannous(II)chloride and 10 mg ascorbic acid under inert conditions. Under vigorous stirring the reaction mixture was heated to 45 oC for 10 min. After cooling down to room temperature the labelling mixture was sterile filtrated (millipore 0.22 μm). Quality control was performed using radio-ITLC (Whatman SG; acetone or ethanol: Rf perrhenate/pertechnetate 0.87, colloid/product 0.05; phys. saline: Rf colloid 0.00, perrhenate/pertechnetate and product 0.9) allowing rapid and efficient assessment of the product. Carrier free [99mTc]-EDTMP and [99mTc]-DPD were prepared according to instructions of the manufacturer. Clinical studies were performed in 29 patients according to a routine bone scanning protocol by injecting 700-800 MBq of the respective tracer and whole body imaging 3 h thereafter. Radiochemical purity and radiochemical yield relied on various parameters such as concentration of carrier and reducing agent and reaction conditions (pH, reaction time, temperature). Means of the labelling yield were 22 % for the preparation using 150 μg of carrier (5 preparations), 80 % for the preparation using 15 μpg of carrier (10 preparations) and 91 % for the carrier free products (5 preparations). Radiochemical purity was >96 % in all experiments. Colloid was formed in very low amounts, and was completely removed by sterile filtration. In clinical studies quantitative analysis demonstrated a significant (p < 0.05) increase in bone/soft tissue ratio and bone lesion/normal bone ratio especially for the preparation using 15 μg of carrier compared to carrier-free products, resulting in a better image quality in patients. This finding of a better uptake in bone tissue could be explained by different complex-parameters such as size, polymerization grade of the radioligand and a mixture of central atoms in the complex as well as stability parameters in the blood compartment. Our new method of 'co-labelling' with a different central atom allows fast and efficient preparation of Re/[99mTc]-EDTMP with high stability, good radiochemical purity and sufficient radiochemical yield. The product offers promising properties for clinical application. (author)