USP Specifications for Routine PET Radiopharmaceuticals

Tests for pyrogens include a rabbit test, in which rabbits are administered with the radiopharmaceutical and their rectal temperatures are monitored. From the rise in temperature in the rabbits, pyrogenicity of a sample is determined. However, a simpler and quicker method is the so-called limsulus amebocyte lysate (LAL) test, also called the bacterial endotoxin test (BET). In this test, the lysate of amebocytes from the blood of the horseshoe crab (Limulus polyphemus) is mixed with the sample and incubated at 37° C. An opaque gel is formed within 15-60 min depending on the concentration of pyrogens. 

Toxicity. The toxicity of a radiopharmaceutical causes alteration in the histology or physiologic functions of an organ or even death of a species after in vivo administration. It is commonly characterized by LD50/60, which is defined as the quantity of a sample that kills 50% of the species within 60 days after administration. It must be established at least in two species before human administration, and the dosage to the humans is decided by a large safety factor. Toxicity arises from the pharmaceutical part and most PET radiopharmaceuticals are not toxic for human administration. 

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