32 Part I Chapter 2 Introduction and goals The radionuclide bone scan is the cornerstone of skeletal nuclear medicine imaging. Bone scintigraphy is a highly sensitive diagnostic nuclear medicine imaging technique that uses a radiotracer to evaluate the distribution of active bone formation in the skeleton related to malignant and benign diseases, as well as physiologic processes. Phosphate analogues can be labelled with technetium-99m (99mTc) and are used for bone imaging because of their high uptake in the skeleton and rapid clearance from soft tissues after intravenous injection. Tracer accumulation occurs in proportion to local blood flow and bone remodeling activity (dependent on osteoblast-osteoclast activity), and unbound tracer is rapidly cleared from surrounding soft tissues. Most pathologic bone conditions, whether of infectious, traumatic, neoplastic or other origins, are associated with an increase in vascularization and local bone remodeling. This accompanying bone reaction is reflected on bone scan as a focus of increased radioactive tracer uptake. Bone scintigraphy is a sensitive technique that can detect significant metabolic changes very early, often appearing several weeks or even months before they become apparent on conventional radiological images. In addition, the technique provides an overview of the entire skeleton at a relatively modest radiation exposure. While MRI has been shown to be more sensitive than planar bone scans in detecting skeletal metastases in vertebral bodies, a comparable diagnostic sensitivity was found with bone SPECT for vertebral body metastases and a higher diagnostic sensitivity for metastases localized in the pedicles [1]. Furthermore, the majority of studies that compared bone scanning with MRI did not use a reliable gold standard and typically included various solid tumors and even lymphomas which usually produce osteolytic lesions with poor osteoblastic bone reaction so that they are not detectable by bone scintigraphy. Hence, there is no reliable evidence that bone scintigraphy is generally less sensitive than whole-body MRI in all solid cancers. Multimodality SPECT/CT offers the unique opportunity to correlate the scintigraphic findings with anatomical images and introduces novel algorithms to further enhance SPECT image quality based on CT data (e.g. correction for attenuation and scatter). This results in improved correlation of areas with physiological variants or abnormal tracer accumulation to anatomical landmarks [2]. However, this has increased the complexity of this technique, increasing the need for standardization and practice guidelines in order to maximize the diagnostic yield of the exam.