Toxicity and dosimetry of177Lu-DOTA-Y3-octreotate in a rat model

Abstract

; 92:628 -633). In the current study, the toxicity and dosimetry of 177 Lu-DOTA-Y3-TATE were determined in both normal and tumor-bearing rats. Doses of 177 Lu-DOTA-Y3-TATE ranging from 0 to 123 mCi/kg were administered to rats and complete blood counts (CBCs) and blood chemistries were analyzed out to 6 weeks. No overt signs of toxicity were observed with 177 Lu-DOTA-Y3-TATE (i.e., lethargy, weight loss, scruffy coat or diarrhea) at any of the dose levels. Blood chemistries and CBCs were normal except for the white blood cell counts, which showed a dose-dependent decrease. The maximum tolerated dose was not reached at 123 mCi/kg. The biodistribution of 177 Lu-DOTA-Y3-TATE was determined in CA20948 rat pancreatic tumor-bearing rats, and the data were used to estimate human absorbed doses to normal tissues. The dose-limiting organ was determined to be the pancreas, followed by the adrenal glands. The absorbed dose to the rat CA20948 tumor was estimated to be 336 rad/mCi (91 mGy/MBq). These data demonstrate that 177 Lu-DOTA-Y3-TATE is an effective targeted radiotherapy agent at levels that show minimal toxicity in this rat model.

αvβ3 Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

“…32, 33 Lewis et al showed kidney absorbed dose (0.670 mGy/MBq) from 177 Lu-DOTA-octreotate dose not indicate any probability of finding radiation damage in the rats kidneys with an injected activity of 555 MBq, leading to a renal dose of 0.37 Gy. 34 Compared to those results, 90 Y-DOTA-c(RGDfK) has the lower kidney absorbed dosimetry (0.568 mGy/MBq). In our radionuclide therapy, a maximum administrated activity were 33.3 MBq (11.1 MBq 3 3), leading to a renal dose of 0.019 Gy.…”

Estimated human absorbed dose for 68Ga-ECC based on mice data: comparison with 67Ga-ECC

“…The discrepancy between different animal models is important, if absorbed dose estimations for humans are derived from animal models. The distribution of a radiopharmaceutical varies not only from rodents to humans, but obviously also between rats and mice [10,39,40] which is obvious even in our previous study on rats [10]. In this study, we predict and compare the absorbed dose from 68 Ga-ECC and 67 Ga-ECC.…”

213Bi-[DOTA0, Tyr3]Octreotide Peptide Receptor Radionuclide Therapy of Pancreatic Tumors in a Preclinical Animal Model

“…The somatostatin receptor -positive rat pancreatic tumor (CA20948) model used in this study is well characterized and has been used in numerous similar studies at different centers to evaluate a variety of radiolabeled somatostatin analogues (29 -31). The doses of 213 Bi-DOTATOC administered for tumor treatment, acute, and chronic toxicity studies were each divided into two injections, separated by a 1-hour interval, to avoid potential mass effects and in consideration of previously established biological half-lives of the octreotide-based somatostatin analogues (27,30). Tumor growth inhibition was observed in both smalland large-volume tumors following treatment with 12.…”