Comparative Pharmacokinetics, Biodistribution and Dosimetry of ²¹²Pb labeled Antibody vs Peptide vs Small Molecule

We study the impact of carrier molecules in biodistribution and absorbed dose in normal tissue and tumors using ²¹²Pb radionuclide. ²¹²Pb (T_1/2 =10.64 hrs) decays to ²¹²Bi (T_1/2 = 60.6 mins) via β emission then finally stable ²⁰⁸Pb via α and γ decays. The effective T_1/2 could vary a lot depending on the carrier molecule. In this study, rats and mice data of ¹³¹I, ¹⁶⁶Ho, ¹⁵³Sm and ¹⁷⁷Lu labeled DOTATATE, ¹¹¹In and ²¹²Pb labelled trastuzumab and ¹⁸⁸Re-HEDP were utilized and fitted via SAAM II software. To calculate absorbed doses, the AUC of each organ was multiplied by the S values provided in MIRD scheme. RBE value of 5 was used to take into account the biological effect of the doses.
The highest level of radioactivity indicating the amount of absorbed dose was detected in bladder, pancreas, intestines, bone and kidneys for DOTATATE, while it was cleared out of the blood within a few hours post injection. In contrast to the peptide carrier, the antibody carrier, remained in the blood significantly longer with increased uptake in the liver after 78 hrs while decreasing everywhere else steadily. For the small molecule carrier HEDP, the main concentration was found in bone followed by kidney, thyroid, stomach, liver and blood. Quantitative analysis of effective doses is in progress.