Synthesis and Preclinical Evaluation of Imaging Abilities of 99mТс-DTPA-GDOF as a New Original Russian Hepatotropic Agent for Scintigraphy and SPECT Studies

Purpose: Was to obtain a radiopharmaceutical (RPH) ‒ 99mTc bound with DTPA-GDOF (2-(2-carboxymethyl-(4-hexa-decyloxyphenyl-carbamoyl-methyl)-aminoethyl)-aminoethyl-(4-hexadecyl-oxyphenyl-carbamoyl methyl)-aminoacetic acid) and evaluate in an in vivo experiment on laboratory rats the possibility of using as hepatotropic RPH for scintigraphy and SPECT. Material and methods: The synthesis of DTPA-GDOF was carried out according to the original method of M.L. Belyanin e.a. at the N.M. Kizhner Center of TPU, by the interaction of 4-hexadecyloxyaniline with diethylenetriaminopentaacetic acid (d-DTPA) anhydride in dimethylformamide medium. Then 2 mg of GDOF-DTPA powder was mixed with 0.5 ml of 5 % sodium bicarbonate solution and heated to 100 oC until completely dissolved. 2 mg of tin dichloride powder were added to the solution, stirred and incubated at 25 oC for at least 20 minutes. The resulting solution was mixed with 99mTc eluate with an activity of 3 MBq and incubated for 10 min at 25 oC. Control of the labelling efficiency of 99mTc with DTPA-GDOF was carried out by chromatography on paper, according to the method of Zimmer and Pavel (1977). An in vivo study of the absorption kinetics of 99mTc-DTPA-GDOF was performed on male rats of the Wistar line (n = 12) 300–350 g. 99mTc-DTPA-GDOF at a dosage of 0.025 mmol/kg, 3 MBq was injected into the femoral vein. All scans are performed using the SPECT/CT Siemens Symbia T. Dynamic planar study included recording 4 sec/frame for the first two minutes, 128 × 128 pixels, and then up to 20 min – as 15 s/frame, followed by a SPECT/CT of the whole body. The value of the fraction of extraction (retention) of RPH in the liver was calculated. The values of the organ accumulation of RPH were determined as the organ fraction of uptake of the agent relative to the total dose administered to the animal Results. The labeling efficiency of DTPA-GDOF with 99mTc in fresh eluate of a standard molybdenum generator was in all cases more than 94 % (on average 95.6 ± 2.1 %, thus the proportion of free technetium was up to 4‒4.5 %). When storing 99mTc-DTPA-GDOF at room temperature on a shelf for up to 5 hours, the release of 99mTc-from the complex with DTPA-GDOF did not exceed 3.1 ± 0.3 %. The extraction fraction of 99mTc-DTPA-GDOF in the liver is as high as 0.78 ± 0.04. The fraction of the injected dose taken up by the liver is up to 70 % (68.9 ± 8.9). The quota of the spleen uptake is 14.1 ± 4.2 %. The level of accumulation of 99mTc-DTPA-GDOF in the liver was then maintained steadily without a significant decrease for up to 16‒18 hours. Conclusion: The 99mTc-DTPA-GDOF complex is a original RFP, with a high 99mTc labeling efficiency, long-lasting stability after labelling, and providing in vivo highly specific long-term imaging of the liver and spleen with gamma scintigraphy and SPECT.