Comparison of the averaged biodistribution and pharmacokinetics between [99mTc]Tc-HYNIC-TOC and [177Lu]Lu-DOTA-TATE in neuroendocrine tumor patients.

BACKGROUND

Accurate pre-therapeutic dosimetry can potentially help optimize peptide receptor radionuclide therapy in patients with neuroendocrine tumors. While positron emission tomography (PET) imaging with [68Ga]Ga-DOTA-peptides has been previously studied for predicting therapeutic absorbed dose, it is limited by its single-time-point nature. In contrast, [99mTc]Tc-HYNIC-TOC offers advantages such as lower cost and multi-time-point imaging capability, but its potential to predict [177Lu]Lu-DOTA-TATE biodistribution remains underexplored. The study objective was to evaluate pharmacokinetics, isolating biological clearance from physical decay effects, and compare relative organ uptake ratios between the compounds. This work lays the foundation for future studies exploring [99mTc]Tc-HYNIC-TOC as a predictive tool for treatment planning - particularly in regions where [68Ga] Ga-DOTA-peptides are less accessible.

MATERIAL AND

METHODS

The study compared the biodistribution and pharmacokinetics of [99mTc]Tc-HYNIC-TOC and [177Lu]Lu-DOTA-TATE in neuroendocrine tumor (NET) patients by modeling pharmacokinetics, analyzing time-integrated activity coefficients, and biological half-lives in the kidneys, liver, spleen, and lesions from 11 diagnostic and 8 therapeutic studies.

RESULTS

[177Lu]Lu-DOTA-TATE showed significantly higher kidney-to-spleen and lesion-to-spleen uptake ratios compared to [99mTc]Tc-HYNIC-TOC, indicating greater relative accumulation in these organs. There was no statistically significant difference in liver-to-spleen uptake between the two compounds. The biological half-life in the kidneys was longer for [99mTc]Tc-HYNIC-TOC than for [177Lu]Lu-DOTA-TATE, suggesting faster renal clearance of the therapeutic agent. Liver and spleen kinetics were comparable between the two tracers.

CONCLUSIONS

While [99mTc]Tc-HYNIC-TOC and [177Lu]Lu-DOTA-TATE show similar biodistribution patterns in the liver and spleen, they differ in renal and lesion uptake and clearance kinetics. The ability of [99mTc]Tc-HYNIC-TOC to capture dynamic behavior through multi-time-point imaging may offer improved prediction of [177Lu]Lu-DOTA-TATE absorbed dose.