Small animal SPECT and its place in the matrix of molecular imaging technologies

Abstract

Molecular imaging refers to the use of non-invasive imaging techniques to detect signals that originate from molecules, often in the form of an injected tracer, and observe their interaction with a specific cellular target in vivo. Differences in the underlying physical principles of these measurement techniques determine the sensitivity, specificity and length of possible observation of the signal, characteristics that have to be traded off according to the biological question under study. Here, we describe the specific characteristics of single photon emission computed tomography (SPECT) relative to other molecular imaging technologies. SPECT is based on the tracer principle and external radiation detection. It is capable of measuring the biodistribution of minute (<10(-10) molar) concentrations of radio-labelled biomolecules in vivo with sub-millimetre resolution and quantifying the molecular kinetic processes in which they participate. Like some other imaging techniques, SPECT was originally developed for human use and was subsequently adapted for imaging small laboratory animals at high spatial resolution for basic and translational research. Its unique capabilities include (i) the ability to image endogenous ligands such as peptides and antibodies due to the relative ease of labelling these molecules with technetium or iodine, (ii) the ability to measure relatively slow kinetic processes (compared with positron emission tomography, for example) due to the long half-life of the commonly used isotopes and (iii) the ability to probe two or more molecular pathways simultaneously by detecting isotopes with different emission energies. In this paper, we review the technology developments and design tradeoffs that led to the current state-of-the-art in SPECT small animal scanning and describe the position SPECT occupies within the matrix of molecular imaging technologies.

Quantification of GABAA receptors in the rat brain with [123I]Iomazenil SPECT from factor analysis-denoised images

“…Long half-lives of radionuclides used in SPECT (e.g. 13.2 h for 123 I, 59.9 days for 125 I, 6 h for 99m Tc) can be exploited for imaging slow kinetic processes, while an in-house radionuclide production facility is not necessary (as opposed to PET, which uses radionuclides with a much shorter half-life) [6]. Furthermore, using isotopes that emit photons with different energy windows enables a simultaneous study of two different processes (e.g.…”

“…Furthermore, using isotopes that emit photons with different energy windows enables a simultaneous study of two different processes (e.g. cerebral blood flow and GABA A receptor distribution for the study of cerebral ischemia) [4,6].…”

“…In the field of translational neuroscience, the potential for in vivo quantification of these receptors in picomolar concentrations with a sub-millimeter resolution can be a powerful tool, given the importance of rodent studies for research on the aforementioned neuropsychiatric conditions [6]. Iomazenil is a high-affinity GABA A receptor antagonist with high brain uptake and specific binding [7,8].…”

“…Labeled with 123 I or 125 I, it has been used as a tracer in human and non-human single-photon emission computed tomography (SPECT). SPECT in small animal research has gained popularity during the past few years as significant progress has been made in the field of small animal imaging instrumentation that has most notably resulted in improvement of its major drawback, limited spatial resolution [6,9,10]. Despite this technical development, several factors degrade SPECT images and limit the potential for quantitative estimations.…”

An enhanced high-resolution EMCCD-based gamma camera using SiPM side detection

“…For introductions to pinhole and small-animal SPECT imaging see e.g. King et al (2002), Meikle et al (2005) and Beekman and Van der Have (2007).…”