68Ga[Ga]-Galmydar: Biodistribution and radiation dosimetry studies in rodents.

Abstract

INTRODUCTION:

68Ga[Ga]-Galmydar is an avid transport substrate of ABCB1 (P-Glycoprotein; 170kDa plasma membrane protein), breast cancer resistance protein (BCRP; ABCG2; 72kDa), penetrates human epidermal carcinoma (KB3-1), breast cancer (MCF7), embryonic kidney (HEK 293) tumor cells and rat cardiomyoblasts, and localizes within the mitochondria of tumor and myocardium cells. 68Ga[Ga]-Galmydar excretes from blood pool quickly, and shows stable retention within rat myocardium in vivo for extended periods, therefore, the agent shows potential to enable myocardial perfusion imaging. The PET tracer also demonstrates ability to probe viability of the blood brain barrier (BBB) in WT mice compared with their mdr1a/1b(-/-) (dKO) and mdr1a/1b/ABCG2(-/-/-) (t-KO) counterparts. Herein, we report dosimetry data for 68Ga[Ga]-Galmydar in mice, and extrapolate that information to determine effective dose (ED) for human studies.

METHODS:

To further assess safety profiles of 68Ga[Ga]-Galmydar for enabling its deployment as a PET imaging probe for biomedical imaging in vivo, we estimated human radiation dosimetry extrapolated from mice biodistribution data. To accomplish this objective, 68Ga[Ga]-Galmydar was injected intravenously into tails, mice were euthanized, organs harvested (5min, 15min, 30min, 60min, 120min), counted, radiation doses to each organ, and whole body were also determined.

RESULTS:

The effective dose (ED) have been found to be 0.021mGy/MBq in males and 0.023mGy/MBq in females. The highest radiation dose was estimated to the kidneys with a value of 0.17mGy/MBq for males and 0.19mGy/MBq for females with contribution from activity in the urine prior to excretion. The critical organ in humans has been determined to be the gall bladder. These data provide preliminary projections on human dosimetry derived from rodent estimates thus providing platform for further validation of dosimetry analysis in human subjects.

CONCLUSIONS:

Combined data obtained from radiation dosimetry studies in mice indicate that 68Ga[Ga]-Galmydar would be safe for further evaluation of dosimetry toxicity and myocardial perfusion PET imaging in humans.

• Authors: Jothilingam Sivapackiam, Richard Laforest, Vijay Sharma
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 59 Pg. 29-35 (04 2018) ISSN: 1872-9614 [Electronic] United States
• PMID: 29454148 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• ((ENB-3-isopropoxy-PIDMP)Ga(III))
• Coordination Complexes

Topics

• Animals
• Coordination Complexes (pharmacokinetics)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Radiometry
• Tissue Distribution