Nuclear Medicine

Single-Photon Emission Tomography

SPECT images are produced by rotation of the gamma camera(s) around the patient to obtain and reconstruct three-dimensional data. By using appropriate collimators and energy windows, SPECT cameras can be employed to image a variety of lower- and higher-energy radionuclides. SPECT scanners can be equipped with CT imaging capability. The CT technology can vary widely—some SPECT/CT scanners have CT detectors built into the rotating gamma camera so that acquisition is slow, and CT images are subject to respiratory motion artifact. Newer SPECT/CT scanners incorporate full multidetector CT technology (similar to PET/CT), enabling faster and higher-quality CT scans to be obtained as part of SPECT/CT imaging. The data obtained from the CT images can be used for attenuation correction of the SPECT images, which enables quantification of the tracer activity. The most recent SPECT technology includes solid-state detectors replacing the previous photomultiplier tubes.

Positron Emission Tomography

PET is a nuclear medicine modality that uses positron emitters such as ¹⁸ F, ¹⁵ O, ¹³ N, ¹¹ C, and ⁶⁸ Ga. The fact that these nuclides are components of common biological molecules makes PET particularly suitable for probing a wide range of biological pathways. With the exception of ¹⁸ F, most positron-emitting radionuclides have a relatively short half-life and generally require an on-site cyclotron or a generator for availability. The longer half-life (110 minutes) of ¹⁸ F has enabled ¹⁸ F PET tracers to be produced commercially at centralized cyclotron facilities and distributed widely for PET imaging.

Currently, the most widely used PET tracer is the glucose analog 2-deoxy-2-[ ¹⁸ F]fluoro-D-glucose (fluorodeoxyglucose [FDG]). FDG-PET has proven efficacy as a general-purpose tracer for staging and restaging a variety of malignancies. FDG-PET can be used to evaluate early response to therapy and is routinely used to guide therapy for some malignancies, most notably lymphoma. While FDG will likely remain a “workhorse” oncology tracer in the foreseeable future, additional PET tracers are available and have recently been approved by the US Food and Drug Administration (FDA) in the United States for imaging of prostate cancer and neuroendocrine tumors. Additional PET biomarkers for hypoxia and receptor imaging are also under investigation.

PET imaging with FDG and other tracers can also provide information about tumor heterogeneity, which can be intratumoral or intralesional. For example, in patients presenting with adenopathy, PET may help define the biopsy target most likely to be diagnostic. In the future, PET imaging with specific target probes can be used as predictive biomarkers prior to targeted therapy.

Basic Physics of Positron Emission Tomography

The radioisotope portion of the molecule used in PET imaging emits a positron (i.e., positively charged electron), which travels a distance of a few millimeters in tissue before it collides with a negatively charged electron. This collision annihilates the entire mass of the positron and electron, generating two photons with energy of 511 keV each. These two photons travel at the speed of light in exactly opposite directions (i.e., 180 degrees apart). Coincident detection of these two photons by two oppositely positioned detectors in the PET scanner results in images with a much higher resolution compared with the conventional, single-photon nuclear medicine studies. More recently, with time-of-flight PET imaging, the detectors have fast time resolution to enable localization along each line of response between the coincidence detectors, further improving quality of the PET images.

PET/CT allows metabolic information from PET to be combined with the anatomic information from CT. PET/CT increases the diagnostic accuracy compared with stand-alone PET. In PET/CT, the patient undergoes a CT scan, followed by a PET scan, without changing the patient's position. PET for most oncological indications is acquired from the base of the skull through the upper thighs. In some instances, such as in melanoma patients, PET is acquired from the vertex of the skull through the toes. The CT portion of PET/CT is acquired within seconds, whereas the PET acquisition time for each bed position (about 15 cm) is several minutes; the total PET acquisition time in newer machines is 15 to 25 minutes.

In addition to delivering anatomic information, the CT portion of PET/CT is used to measure the attenuation of the x-ray photons traveling through the patient to produce the so-called attenuation map and correct the PET data for tissue attenuation. During PET acquisition, photons from structures deep in the abdomen or pelvis are more strongly attenuated than those from superficial structures and the chest. The intensity of uptake in deeper structures is underestimated on nonattenuation-corrected PET images; the intensity of uptake in the deeper structures is normalized to the intensity of uptake in the superficial structures on the attenuation-corrected PET images ( Fig. 12.1 ). Attenuation correction of the PET data is also a prerequisite for quantification of radiotracer uptake in PET/CT scans.

Spatial alignment between the PET and CT scans is crucial both for correct anatomic localization and accurate quantification. Misalignment may be caused by the changed position of a body part (e.g., neck, legs) or physiological changes in the position of an organ (e.g., respiratory movement, bladder filling, bowel peristalsis) between the CT scan and PET scan. The most commonly encountered problem occurs at the lung bases because CT is obtained over a short time interval and PET images are acquired with the patient quietly breathing. This respiratory misregistration can be minimized by acquiring the CT scan with respiration suspended in quiet end expiration. Because the degree of misalignment and resulting mislocalization can be significant, the radiologist must be cautious when interpreting or quantifying the attenuation-corrected PET/CT images or using PET/CT images for radiation therapy planning. The magnitude of this misalignment can be assessed by using the fusion display of the nonattenuation-corrected PET images with CT. In the case of significant misalignment, the nonattenuation-corrected PET images should be reviewed without fusion with CT, and the metabolic findings on PET should be correlated side by side with the anatomic findings on CT ( Fig. 12.2 ).

Current PET/CT scanners are equipped with multidetector CT (MDCT) and have full diagnostic CT capabilities that are equivalent to stand-alone CT scanners. This enables comprehensive PET/CT examinations to be performed that combine PET with fully diagnostic contrast-enhanced CT. MDCT allows reconstruction to be performed using isotropic voxels, enabling multiplanar display of CT images with full spatial resolution. This provides optimal definition of target lesions as well as morphological characterization and, therefore, can maximize the diagnostic capabilities of combined PET/CT imaging.

PET-MR has been introduced clinically relatively recently, which offers the ability of obtaining PET images with MRI and fusion of that information. MRI provides superior soft-tissue contrast compared with CT. In addition, advanced imaging sequences—such as diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE-MRI) permit quantitative physiological information to complement the PET radiotracer information. MRI is also used to calculate attenuation correction for the PET images. Because MRI is limited in its ability to visualize bone and does not use photons, quantification of uptake on PET images may be less accurate compared with PET/CT. However, MRI has diagnostic advantages over CT in evaluating the brain, head and neck, and pelvis; clinical applications for PET/MRI are currently being developed. Another advantage of MRI is that there is no associated ionizing radiation; thus, PET/MRI may have additional applications in the pediatric population.

General Aspects of Tumor Visualization on FDG-PET

FDG is currently the most widely used radiotracer in clinical PET imaging. Tumor imaging with FDG is based on the principle of increased glucose metabolism of cancer cells, which are more dependent on anaerobic glycolysis (Warburg effect). Like glucose, FDG is taken up by the cancer cells through facilitative glucose transporters (GLUTs). Once in the cell, glucose or FDG is phosphorylated by hexokinase to glucose-6-phosphate or FDG-6-phosphate, respectively. Expression of GLUTs and hexokinase, as well as the affinity of hexokinase for phosphorylation of glucose or FDG, is generally higher in cancer cells than in normal cells. Glucose-6-phosphate travels farther down the glycolytic or oxidative pathways to be metabolized, in contrast to FDG-6-phosphate, which cannot be metabolized. In normal cells, glucose-6-phosphate or FDG-6-phosphate can be dephosphorylated and exit the cells. In cancer cells, however, expression of glucose-6-phosphatase is usually significantly decreased, and glucose-6-phosphate or FDG-6-phosphate therefore can become only minimally dephosphorylated and remains in large part within the cell. Because FDG-6-phosphate cannot be metabolized, it is trapped in the cancer cell as a polar metabolite; thus, it constitutes the basis for tumor visualization on FDG-PET scans.

The intensity of a malignant tumor on PET is dependent on the histology and number of malignant cells in the tumor mass. Hodgkin lymphoma and melanoma are markedly intense on FDG-PET. Other tumors, such as bronchioloalveolar lung cancer, mucinous adenocarcinomas, or mucosal-associated lymphoid tissue (MALT) lymphomas, may have only modest FDG activity. In addition, FDG is also taken up in benign processes such as infection and inflammation because white blood cells and fibroblasts are highly avid for FDG. The major causes for false-positive and false-negative FDG-PET activity are summarized in Box 12.1 .