Uptake of 99mTc-labeled monocationic tracers in thyroid tissue. A comparison of in-vitro and in-vivo data

Tetrofosmin and furifosmin are 99mTc-labeled, lipophilic, monocationic tracers originally developed for myocardial perfusion imaging. Both radiopharmaceuticals found additional applications as they are taken up by different types of tumor tissue, enabling imaging of these lesions in patients. In particular 99mTc-tetrofosmin was found to have an elevated in-vivo uptake with high sensitivity and specificity for breast- and lung cancer, parathyroid adenomas and melanoma. In the follow-up of differentiated thyroid cancer after thyroidectomy 99mTc-tetrofosmin scintigraphy meanwhile became a reliable alternative to iodine-131 scintigraphy. For primary diagnosis, in contrast, the in-vivo data available so far, are very poor. Very little is, however, known about the uptake mechanisms of these tracers in thyroid tissue. In this study thyroid tissue, collected from patients who underwent thyroidectomy, was incubated in-vitro with 99mTc-tetrofosmin and 99mTc-furifosmin up to 60 minutes at constant conditions of 37oC, 95 % O2 and 5 % CO2 with a total tracer activity of 10μCi per sample. The in-vitro uptake was measured in the gamma counter and the results were then compared with the in vivo scintigraphy of the patients the tissue was derived from. The results of the in-vitro experiments show a very low uptake for tetrofosmin and furifosmin for all the incubation periods. In struma nodosa tissue the mean uptake of tetrofosmin was 0.07 % ± 0.02 % per mg tissue, 0.06 % ± 0.042 % was the mean uptake of furifosmin, remaining unchanged from 5 to 60 minutes of incubation. The in-vitro uptake of 99mTc-tetrofosmin in papillary and follicular cancer tissue is low, but significantly elevated when compared to struma nodosa tissue. The mean uptake in thyroid cancer tissue is ranging between 0.38 % and 1.31 %, however, statistical analysis does not reveal significant differences when comparing the uptake in papillary and in follicular thyroid cancer tissue. Comparing 99mTc-tetrofosmin and 99mTc-furifosmin, the in-vitro uptake of furifosmin in papillary cancer tissue is quite low, but even significantly higher than the uptake of tetrofosmin. In-vivo studies, however, reveal a clear superiority of 99mTc-tetrofosmin scintigraphy. Both tracers show a low, but continuously increasing in-vitro uptake ratio from 5 to 60 minutes incubation in thyroid cancer tissue. The results of the in-vitro experiments with 99Tc-tetrofosmin have then been compared to the 99mTc-tetrofosmin in-vivo scintigraphy of the same patient. No significant correlation between results of the in-vivo 99mTc-tetrofosmin scintigraphy and the findings in-vitro could be discovered. Conclusions for an optimal in-vitro imaging protocol or the biochemical uptake mechanism can therefore not be drawn. (author)