We offer a state-of-the-art service for all kinds of early phase trials that involve radiolabelled IMP or ‘challenge agents’ – sometimes known as ‘non-IMP’.
We have our own ARSAC (Administration of Radioactive Substances Advisory Committee) licence holder with more than 30 years’ experience of the clinical use of radiolabelled substances, and HMR has been executing trials of radiolabelled materials successfully since the company was founded.
Our ADME (Absorption, Distribution, Metabolism, Elimination) trials mostly involve 14C(carbon-14)-labelled IMP, but we also have experience with radionuclides such as 125I (iodine-125) and 3H (tritium). Unusually, we’ve also worked with the stable isotope 2H (deuterium). In all of our 50 or so ADME trials, we’ve invariably succeeded in recovering almost all the administered dose of radioactivity. That immaculate record is a reflection of our attention to detail and our dedicated efforts to ensure that all our faecal and urine collections are 100% complete.
Microdosing and ‘light label’ radioactivity
It’s very helpful to measure the absolute bioavailability of an IMP as early as possible in its development. We now have substantial experience of doing just that, using a therapeutic oral dose of unlabelled (‘cold’) IMP followed by an intravenous microdose of IMP bearing a ‘light label’ of radioactivity. The ‘cold’ IMP is assayed by conventional methods such as LC/MS/MS, and the radiolabelled IMP is assayed using Accelerated Mass Spectrometry (AMS). The microdose is so small that it neither interferes with the assay of the oral, ‘cold’ IMP, nor does it pose any threat to health; the tiny amount of radioactivity used is equally safe, and approval by the regulatory authority (ARSAC) is usually a formality.
Microdoses of ‘lightly labelled’ IMP can also be used to select, from among competing compounds, the one with the most favourable pharmacokinetics.
Radiolabelled challenge agents
We use our expertise and experience to minimise the exposure of our volunteers and patients to ionising radiation. So, whenever possible, we use non-radioactive substances as challenge agents and probes. However, some techniques depend upon the use of radionuclides, and we have plenty of experience of using materials labelled with the lowest feasible quantities of 51Cr, 99mTc and 125I.
We have a dedicated radiopharmacy, including an aseptic suite for preparing radiopharmaceuticals. We prepare injections and intravenous infusions, and do terminal sterilisation by a validated filtration procedure.
We use on-site liquid scintillation counting (LSC) to QC our radiolabelled formulations. We also use LSC to quantify IMP adsorbed to the materials used in its preparation, such as plastic tubing and filters.
On our wards, we strictly segregate areas used for trials of ‘light label’ radioactivity and conventional doses of radionuclides. The same strict segregation is applied in the HMR laboratory, where the samples are processed.
In every department, we have highly experienced staff: clinical, pharmacy, laboratory and quality assurance. We have an ARSAC licence holder and several Radiation Protection Supervisors on-site, and an external Radiation Protection Adviser with University Hospital experience at a senior level.
We hold an Environment Agency licence to store and dispose of radioactive materials. Our ARSAC licence holder is on-site.
From HMR, it’s a short walk to the Central Middlesex Hospital, where we commission a wide range of radiographic examinations.
Positron emission tomography (PET)
PET can yield invaluable information about the receptor affinity and occupancy of an IMP, and may guide both size and frequency of therapeutic doses. We use our expertise to select, screen, dose and supervise the experimental subjects, and we do the PET scans in collaboration with Invicro at Hammersmith Hospital. Invicro have extremely sophisticated skills and equipment, and offer a world-class imaging service in drug development.
Functional Magnetic Resonance Imaging (fMRI)
In addition to PET, Invicro are also highly experienced in fMRI. Our remarkable combination of facilities allows us to do trials that combine PET with fMRI, whenever required.
We collaborate with academic, NHS and private units as necessary, to offer a comprehensive echocardiography service – including cardiac and transvaginal examinations.