Prostate Cancer Medical Imaging Drugs

Prostate Cancer

Medical Imaging Drugs from Lab to Human Exposure

New techniques: Medical imaging drugs

Currently, drugs used for Positron Emission Tomography (PET) are subject to additional regulations by the FDA. "PET images show the chemical functioning of an organ or tissue and are unlike X-ray or MRI images, which show only body structure" (PET: Q&A, 2011, FDA). These drugs have been deemed to be sufficiently distinct by the FDA from traditional pharmaceuticals, regarding their potential for complications, that they warrant their own regulations due to the fact that "PET drug exhibits spontaneous disintegration of unstable nuclei by the emission of positrons" (Guidance, 2009, FDA). All drugs must proceed through a series of phases of testing from lab to market. Clinical trials must demonstrate that PET drugs are harmless despite the fact that the drugs contain small amounts of radioactive materials.

According to the FDA a "diagnostic radiopharmaceutical means: (a) An article that is intended for use in the diagnosis or monitoring of a disease or a manifestation of a disease in humans and that exhibits spontaneous disintegration of unstable nuclei with the emission of nuclear particles or photons; or (b) Any nonradioactive reagent kit or nuclide generator…. The amount of new safety data required will depend on the characteristics of the product and available information regarding the safety of the diagnostic radiopharmaceutical, and its carrier or ligand, obtained from other studies and uses. Such information may include, but is not limited to, the dose, route of administration, frequency of use, half-life of the ligand or carrier, half-life of the radionuclide, and results of clinical and preclinical studies. (CFR, 2010, FDA)

Before testing on humans, PET drugs are commonly tested on rats. Because PET drugs involve submitting the patient to a specific procedure, the pre-human clinical trials must not simply test the drugs, but also examine the drug's utility and safety over the course of the procedure. More sophisticated tests have been enabled by new technology. Now "in pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals. The uptake of the drug, the tissues in which it concentrates, and its eventual elimination, can be monitored far more quickly and cost effectively than the older technique of killing and dissecting the animals to discover the same information. A miniature PET tomograph has been constructed that is small enough for a fully conscious and mobile rat to wear on its head while walking around" (PET, 2011, New World Encyclopedia). The animals can then be tested for short-term and long-term health effects as a consequence of the drug's administration and the trials have the advantage of featuring the experience of testing the drug under real-world conditions. Rats are commonly used for their size (creating the animal-sized scanners is so expensive they are commonly not used in veterinary medicine even for dogs and cats) and the fact that rats breed quickly (PET, 2011, New World Encyclopedia). Lab rats have also been bred to ensure that they have similar enough genetic profiles to the humans the drugs will eventually be used upon, and even more specific populations have been bred to manifest the types of cancers detected by PET scans. Acute toxicity studies are ideally conducted using the means of transmission deployed with the eventual human subjects, which this new technology permits.

According to FDA guidelines, the minimum amount of animals should be used to determine toxicity, contrary to previous ways of determining potential lethality. "Animals should be observed for 14 days after pharmaceutical administration. All mortalities, clinical signs, time of onset, duration, and reversibility of toxicity should be recorded. Gross necropsies should be performed on all animals, including those sacrificed moribund, found dead, or terminated at 14 days" (Guidance, 2006, CDER).