Evaluation of three different 99m Tc-based mock-venom agents for lymphoscintigraphy studies in preclinical models of peripheral snakebite envenomation

Snakebite envenomation is one of the major public health concerns across many countries; with the WHO designating it as a 'priority neglected tropical disease' and stressing for a need to develop novel therapeutic strategies to reduce death and disability rate by end of 2030. Since a major...

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Published in:Journal of pharmacological and toxicological methods 2023-07, Vol.122, p.107280
Main Authors: Tiwari, Nidhi, Jaimini, Abhinav, Jain, Gaurav Kumar, Aggarwal, Geeta, Mittal, Gaurav
Format: Article
Language:English
Subjects:
Animals
Humans
Lymph Nodes
Lymphoscintigraphy
Radiopharmaceuticals - pharmacology
Rats
Rats, Sprague-Dawley
Snake Bites - diagnostic imaging
Sulfur Compounds
Technetium Tc 99m Sulfur Colloid
Venoms
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Summary:Snakebite envenomation is one of the major public health concerns across many countries; with the WHO designating it as a 'priority neglected tropical disease' and stressing for a need to develop novel therapeutic strategies to reduce death and disability rate by end of 2030. Since a major component of venom; the high molecular weight (HMw) toxins enter the bloodstream through lymphatic system, research is focusing on modulating the lymphatic flow rate after topical application of suitable drug candidates. Present study compared the suitability of three radiopharmaceutical agents, namely Tc-Sulfur colloid (SC), Tc-Phytate (Phy) and Tc-Human serum albumin (HSA), to be used as mock-venom agent in studying modulation in lymphatic flow rate in preclinical models of peripheral snakebite envenomation using lymphoscintigraphy studies. The study was performed in 72 Sprague Dawley rats; divided into six groups of 12 rats each. Control groups were given intradermal injection (1.29-1.48 MBq in 100 μl normal saline) of either Tc-Phy/ Tc-SC/ Tc-HSA into the tail as 'mock-venom'. In respective test groups, commercially available topical formulation (Anobliss® Cream) containing Nifedipine (Nif; 0.3% w/w) and Lidocaine (Lid; 1.5% w/w) was applied topically over the animals' lower body (tail and hind limbs) immediately within 20s of administering intradermal injection of the radiopharmaceutical. Any modulation in lymph transit time from periphery to systemic circulation was assessed using lymphoscintigraphy by taking dynamic gamma-scintigraphy images of 60s each till 1 h post-injection of the test radiopharmaceuticals. Significant difference in movement of the three radiopharmaceuticals was noted in terms of their lymphatic movement. Tc-Phy did not show significant travel through the lymphatics and the liver was faintly visualized in control as well as test intervention groups. In case of Tc-SC, significant changes in movement of the radiotracer after topical application of Nif/Lid in the test intervention groups were clearly noted in comparison to control (P 
ISSN:1873-488X