Biodistribution of ^99mTc-HYNIC-lactadherin in mice – a potential tracer for visualizing apoptosis in vivo

Abstract

Introduction. The aim of this study was to establish a radio synthesis of ^99mTc-HYNIC-lactadherin for in vivo studies and to perform biodistribution analysis studies in mice, comparing ^99mTc-HYNIC-lactadherin to ^99mTc-HYNIC-annexin V. Methods. The radiochemical purity of ^99mTc-HYNIC-lactadherin was optimized by varying the amount of SnCl₂ in the synthesis. Furthermore, the need for bovine serum albumin (BSA) as a stabilizing agent was evaluated by following the stability by radiochemical purity measurement with and without the addition of BSA. A total of 24 mice were assigned to groups of 15 and nine mice, respectively. The animals were sacrificed at different time points; 10 min, 60 min, and 180 min. Results. The synthesis of ^99mTc-HYNIC-lactadherin for in vivo studies has been optimized to give a stable product without addition of BSA and with a radiochemical purity of more than 95%. Approximately 60% of the injected dose of ^99mTc-HYNIC-lactadherin was found in the liver and 4–5% could be assigned to kidneys. In contrast, ^99mTc-HYNIC-annexin V distributes with around 13% and 45% of the injected dose in liver and kidneys, respectively. Over the experimental period (10–180 min) only small distributional changes were observed for both probes. Conclusion. In conclusion, the biodistribution of ^99mTc-HYNIC-lactadherin, a potential new tracer for in vivo quantification of apoptosis, was evaluated. The small renal uptake of ^99mTc-HYNIC-lactadherin makes it possible to image apoptosis in the kidneys, but the high liver clearance may be a disadvantage during myocardial perfusion.

Key Words::

• Annexin V
• imaging
• lactadherin
• technetium
• hydrazine nicotinamide
• apoptosis

Acknowledgement

The Danish Medical Research Council (09-060110), The Danish Cancer Society (DP07002), Milk Research Consortium (26-04-0249) and PhD school for Industrial Related Molecular Biotechnology (646-03-0011) are acknowledged for financial support. Lene Elsebeth Nielsen, Inger Marie Horsman, Pia Schjerbeck, Margit Skriver Rasmussen and Anni Bojsen are also thanked for their technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.