Oncological molecular imaging: nuclear medicine techniques

Abstract

With the expanding interest and development in molecular biology, nuclear medicine imaging, essentially a molecular imaging technique studying biological processes at the cellular and molecular level, has much to offer. As other non-isotope techniques develop there has also been an opportunity for nuclear medicine to broaden its horizons in this field. Nuclear medicine’s involvement in molecular imaging has been enhanced by the improvement in single photon emission computed tomography (SPECT), the wider availability of positron emission tomography (PET) and a greater input and new developments in radiochemistry. Nuclear medicine can be regarded as a method by which biological processes may be non-invasively monitored by radiopharmaceuticals delivered in tracer amounts. By measuring radioactive concentrations in tissue samples, either directly or by means of imaging, it is possible to explore and quantify biological processes in health and disease at the molecular or cellular level. The major advantage of nuclear medicine methods is that only picomolar concentrations of radiotracers are required to provide a measurable signal without interfering with the process under investigation. It is often true that biochemical or metabolic changes can therefore be identified before a significant change in structure or anatomy can be determined. In oncology this has the potential advantage of not only being able to detect abnormal function related to malignant tissue at diagnosis but also to identify changes as a result of therapy earlier than is possible with anatomical techniques alone. However, this high sensitivity is often at the expense of inferior spatial resolution. Here PET techniques show advantages over SPECT, as not only is spatial resolution better, but positron emitting radionuclides include isotopes of carbon (C), nitrogen (N) and oxygen (O), allowing radiolabelling of biological compounds of interest. SPECT relies more frequently on the use of radiolabelled analogues. The spatial resolution of PET remains inferior to that of anatomical techniques including CT, MRI and ultrasound but with the advent of combined dual-modality scanners, such as PET/CT, it is possible that some of the disadvantages of the two techniques may be minimized and the advantages maximized. Another potential disadvantage of SPECT and PET techniques is that the measured signal is not chemically specific; for example, it is not possible to differentiate signal between the administered radiopharmaceutical and its metabolites without more complex metabolite analysis in blood. Due to the spatial resolution advantages of PET over SPECT, coupled with an ability to more accurately correct for attenuation of photons, quantitative accuracy is superior with PET. Absolute measurements of radioactive concentrations in tissue over time allow the measurement of dynamic processes in absolute units such as ml min ml. Realistic goals of nuclear medicine in oncological molecular imaging are to develop high affinity, high specific activity radiopharmaceuticals, allowing quantitation of molecular processes in whole tumour in a reproducible and repeatable manner. In oncology there are a number of areas where nuclear medicine techniques may give information on molecular and cellular events, many of which are already absorbed into routine clinical practice and others that are at a more developmental stage. These applications include the detection and measurement of a number of events in untreated tumours, including glycolysis, proliferation, membrane synthesis and receptor expression, amongst many others. In treated tumours there are methods to nonspecifically measure the downstream effect of cytotoxic therapies but with the development of molecular therapies targeting specific aspects of cancer cell biology there is a greater interest in the development of markers aimed at specifically measuring the molecular consequence of each therapeutic agent. For example, a marker to measure the amount of tumour angiogenesis is likely to be a more sensitive measure of response to an antiangiogenic agent than a non-specific marker of downstream effects such as tumour cell viability. Molecular imaging techniques may also allow us to tailor therapy to individual patients. Visualization of specific molecular targets prior to therapy may identify patients most likely to benefit from a particular molecular therapy. Many novel anticancer therapies are cytostatic rather than cytotoxic and conventional methods of measuring treatment response may be particularly insensitive when tumour shrinkage is not anticipated but where functional changes may be marked. It is here that nuclear medicine techniques also have a role to play and it is important that molecular imaging techniques are developed in conjunction with molecular therapeutics for some of the reasons stated above. Additionally, in nuclear medicine there is the opportunity to label specific molecular probes with a or b emitting radionuclides to deliver a therapeutic dose of targeted radiation to abnormal cells that concentrate these radiopharmaceuticals whilst minimizing radiation dose to normal tissues.