Laurie Jones-Jackson

18F-Fluorodeoxyglucose Positron Emission Tomography Contributes to the Diagnosis and Management of Infections in Patients With Multiple Myeloma: A Study of 165 Infectious Episodes

PURPOSE Correctly identifying infection in cancer patients can be challenging. Limited data suggest that positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may be useful for diagnosing infection. To determine the role of FDG-PET in the diagnosis of infection in patients with multiple myeloma (MM). PATIENTS AND METHODS The medical records of 248 patients who had FDG-PET performed for MM staging or infection work-up revealing increased uptake at extramedullary sites and/or bones and joints that would be atypical for MM between October 2001 and May 2004 were reviewed to identify infections and evaluate FDG-PET contribution to patient outcome. RESULTS One hundred sixty-five infections were identified in 143 adults with MM. Infections involved the respiratory tract [99; pneumonia (93), sinusitis (six)], bone, joint and soft tissues [26; discitis (10), osteomyelitis (nine), septic arthritis (one), cellulitis (six)], vascular system [18; septic thrombophlebitis (nine), infection of implantable catheter (eight), septic emboli (one)], gastrointestinal tract [12; colitis (seven), abdominal abscess (three), and diverticulitis and esophagitis (one each)], and dentition [periodontal abscess (10)]. Infections were caused by bacteria, mycobacteria, fungi, and viruses. FDG-PET detected infection even in patients with severe neutropenia and lymphopenia (30 episodes). The FDG-PET findings identified infections not detectable by other methods (46 episodes), determined extent of infection (32 episodes), and led to modification of work-up and therapy (55 episodes). Twenty silent, but clinically relevant, infections were detected among patients undergoing staging FDG-PET. CONCLUSION In patients with MM, FDG-PET is a useful tool for diagnosing and managing infections even in the setting of severe immunosuppression.

Imaging of Multiple Myeloma and Related Plasma Cell Dyscrasias

Multiple myeloma (MM) is an incurable plasma cell malignancy of the bone marrow. MM has 3 components: diffuse marrow infiltration, focal bone lesions, and soft-tissue (extramedullary) disease. The hallmark biomarker in blood or urine is a monoclonal immunoglobulin, the monoclonal protein. Waldenstrom macroglobulinemia is a similar disease with secretion of IgM. Staging is classically performed with the 1975 Durie–Salmon system, which includes conventional radiographs. Recently updated, the Durie–Salmon Plus staging system includes CT, MRI, and 18F-FDG PET/CT. The hallmark radiographic lesion of symptomatic MM is a well-demarcated, focal osteolytic bone lesion. The number of focal bone lesions correlates inversely with outcome. Extramedullary disease is typically an aggressive, poorly differentiated form of MM that confers inferior outcome, with median survival of less than 1 y if present at diagnosis. Achievement of a complete response on 18F-FDG PET before stem-cell transplantation correlates with a superior outcome.

Safety and Efficacy of 68Ga-DOTATATE PET/CT for Diagnosis, Staging and Treatment Management of Neuroendocrine Tumors

Our purpose was to evaluate the safety and efficacy of 68Ga-DOTATATE PET/CT compared with 111In-pentetreotide imaging for diagnosis, staging, and restaging of pulmonary and gastroenteropancreatic neuroendocrine tumors. Methods: 68Ga-DOTATATE PET/CT and 111In-pentetreotide scans were obtained for 78 of 97 consecutively enrolled patients with known or suspected pulmonary or gastroenteropancreatic neuroendocrine tumors. Safety and toxicity were measured by comparing vital signs, serum chemistry values, or acquisition-related medical complications before and after 68Ga-DOTATATE injection. Added value was determined by changes in treatment plan when 68Ga-DOTATATE PET/CT results were added to all prior imaging, including 111In-pentetreotide. Interobserver reproducibility of 68Ga-DOTATATE PET/CT scan interpretation was measured between blinded and nonblinded interpreters. Results: 68Ga-DOTATATE PET/CT and 111In-pentetreotide scans were significantly different in impact on treatment (P < 0.001). 68Ga-DOTATATE PET/CT combined with CT or liver MRI changed care in 28 of 78 (36%) patients. Interobserver agreement between blinded and nonblinded interpreters was high. No participant had a trial-related event requiring treatment. Mild, transient events were tachycardia in 1, alanine transaminase elevation in 1, and hyperglycemia in 2 participants. No clinically significant arrhythmias occurred. 68Ga-DOTATATE PET/CT correctly identified 3 patients for peptide-receptor radiotherapy incorrectly classified by 111In-pentetreotide. Conclusion: 68Ga-DOTATATE PET/CT was equivalent or superior to 111In-pentetreotide imaging in all 78 patients. No adverse events requiring treatment were observed. 68Ga-DOTATATE PET/CT changed treatment in 36% of participants. Given the lack of significant toxicity, lower radiation exposure, and improved accuracy compared with 111In-pentetreotide, 68Ga-DOTATATE imaging should be used instead of 111In-pentetreotide imaging where available.

New imaging tools for the diagnosis of infection

Infection imaging became widespread in 1971 with the release of 67Ga citrate. Multiphase skeletal scintigraphy and radiolabeled white blood cells (WBCs) have since become the most widespread clinically used agents for the imaging of infection. A wide variety of other radiolabeled probes are under investigation, based on antibodies, cytokines, assorted proteins and other molecules, alone or in various combinations. However, these latter agents, with a few exceptions, are not routinely used clinically. Radiolabeled ciprofloxacin represents the first attempt to develop an infection-specific imaging agent (most infection-imaging probes localized nonspecifically to inflammation as well), but it has not proven superior to radiolabeled WBCs or 18F-fluoro-deoxy-glucose (FDG) PET. Because of the ability to combine exquisite anatomic detail with focal uptake of 18F-FDG, PET-computed tomography has achieved great success in the detection and localization of infection, including in clinically adverse conditions. Despite these advances, at this time an infection-specific imaging agent does not exist.

PET and PET/CT Imaging in Multiple Myeloma, Solitary Plasmacytoma, MGUS, and Other Plasma Cell Dyscrasias

In MM and related plasma cell dyscrasias, FDG-PET or PET/CT imaging are useful and reliable techniques for assistance in the diagnosis by identifying optimal sites for biopsy, for staging and restaging the tumor, for detecting extramedullary disease, and for monitoring response to treatment. They are equally effective in secretory or nonsecretory disease, with the latter developing with an increasing frequency during the course of the disease, causing difficulty in monitoring disease response or progression.

Imaging of Multiple Myeloma, Solitary Plasmacytoma, MGUS, and Other Plasma Cell Dyscrasias

The significance of medical imaging in multiple myeloma was established in 1975 with the classic description of the Durie–Salmon staging system which incorporated the presence and number of focal osteolytic lesions in the staging scheme. A third of a century later, this staging system remains in use, though augmented by advances in medical imaging. By the early 1980s, CT imaging demonstrated more focal bone lesions than were seen with standard radiographs as well as extramedullary disease. By the 1980s, MRI imaging revealed skeletal disease that was not apparent by either standard x-rays or CT, focal plasmacytomas in bone that had not yet produced focal osteolysis, and diffuse marrow infiltration. Subsequent work throughout the 1990s developed and established MRI as a very powerful tool to demonstrate the full extent of skeletal disease with resolution approaching a few millimeters. MRI was also used to direct biopsies of focal lesions which increased the detection rate of clinically relevant information compared to random marrow biopsies. However, standard MRI lacked the wide field of view of CT and was both considerably more expensive and less widely available than CT. An additional weakness of standard x-rays, CT, and MRI was their limited utility in the demonstration of response to treatment. By the mid- to late 1990s, the utility of 18F-FDG PET and (after 2000) PET/CT was apparent. PET/CT was particularly powerful since it provided a “whole-body” examination combining the utility of CT (“anatomy”) with a “metabolic” image that was linked to the Warburg physiology of tumors, at a fraction of the cost of an extensive MRI. Thus, PET and PET/CT can demonstrate both active disease and, very importantly, response to treatment. The PET image fused to the CT portion of the PET/CT also provides a “free” whole-body metastatic bone survey that can reveal not only focal bone lesions but also additional clinically relevant findings (fractures or impending fractures, additional malignancies, occult infections, unsuspected regions of tumor involvement such as extramedullary tumor). Recent work has established the fundamental importance of 18F-FDG PET and PET/CT for the baseline evaluation of patients with multiple myeloma and related plasma cell dyscrasias, as well as for subsequent evaluations related to patient management. Future directions for imaging research in multiple myeloma will include PET imaging with isotopes other than 18F-FDG and whole-body MRI.

PET-CT Imaging in Multiple Myeloma, Solitary Plasmacytoma, and Related Plasma Cell Dyscrasias

In multiple myeloma and related plasma cell dyscrasias, either FDG PET or PET-CT imaging is useful and reliable technique for diagnosis by identifying optimal sites for biopsy, for staging and restaging the tumor, for detecting extramedullary disease and monitoring response to treatment, though PET-CT is superior for precise localization of regions of involvement, discrimination between infection and tumor, and detection of important additional findings, such as epidural disease, spinal cord compression, lytic bone disease (including areas at risk for fracture), etc. FDG PET and PET-CT are equally effective in either secretory or nonsecretory disease, with the latter developing with an increasing frequency during the course of the disease, causing difficulty in monitoring disease response or progression via laboratory means. FDG PET or PET-CT imaging is also useful techniques for detecting occult infection in patients with hematologic malignancies, for finding the source of infection and documenting response to treatment of infection, even in the setting of severe neutropenia/immunosuppression.