Whole-Body ¹⁸F-FDG PET Identifies High-Risk Myeloma

Clinical Data

Between July 1996 and July 2000, 98 whole-body ¹⁸F-FDG PET scans were obtained for 66 patients with multiple myeloma or related monoclonal gammopathies. We undertook a retrospective review of the 98 whole-body scans; 33 used dedicated PET, 39 used coincidence SPECT, and 26 used collimated SPECT. Sixteen patients had previously untreated active myeloma, 10 patients were in remission, 26 patients had relapsing disease, and 14 patients had monoclonal gammopathy of undetermined significance (MGUS) or primary systemic amyloidosis without myeloma. Twenty-five patients had 2 or more whole-body scans for monitoring.

The whole-body ¹⁸F-FDG PET was used in addition to standard testing to assess disease stage and activity for baseline evaluation or for follow-up monitoring. The whole-body ¹⁸F-FDG PET results were compared with radiologic skeletal surveys as the primary comparison. Additional imaging such as MRI and CT was used adjunctively to confirm or clarify sites of suspected disease. Six patients had direct biopsy of suspected sites as a basis for local irradiation therapy. All patients had standard blood and urine testing including use of M component measurements and serum β₂-microglobulin to determine disease status in addition to the clinical findings (12).

Whole-Body ¹⁸F-FDG PET

All patients underwent whole-body ¹⁸F-FDG surveys using either a dedicated PET system (CPET; ADAC Laboratories, Milpitas, CA [33 scans]), a coincidence camera (MCD; ADAC Laboratories [39 scans] ), or a collimated SPECT system (Meditech; Park, U.K. and Canada [26 scans]). All patients fasted for a minimum of 6 h before their ¹⁸F-FDG whole-body study. For dedicated PET, patients received a 170.2-MBq injection of ¹⁸F-FDG and were scanned 90 min after injection. A minimum of 6 bed positions was obtained, with a 50% overlap. Whole-body scans, including attenuation correction, required approximately 1 h of imaging time. Coincidence studies were performed after 222–296 MBq of ¹⁸F-FDG and a delay of approximately 3 h before scanning. Three overlapping bed positions were obtained, with scan times of approximately 2 h, for a whole-body study. Collimated studies were performed after 370–444 MBq of ¹⁸F-FDG, using 2 nonoverlapping bed positions, for a whole-body survey. The total scan time was approximately 2 h.

Images were reconstructed using iterative algorithms and were interpreted in a masked fashion by 2 observers using computer displays consisting of volume-rendered images and coronal, sagittal, and transverse images of the entire body. For the dedicated PET and coincidence studies, attenuation-corrected and non-attenuation-corrected images were interpreted.

Areas of focal uptake were interpreted as positive for myeloma unless they were at sites of known accumulation, including the kidney and bladder, gastrointestinal tract, and certain skeletal areas showing symmetric joint uptake, especially within the shoulder girdle. A diffuse increase in bone marrow activity was interpreted as positive for myeloma if the intensity of activity relative to the background was considered greater than that seen using comparable imaging in patients without bone marrow disease.

Previously Untreated Active Myeloma

All 16 patients (100%) with previously untreated active myeloma had positive scan findings. Thirteen (81%) of 16 had both focal and diffuse increased bone marrow uptake on the scan, whereas 3 (19%) of 16 had diffuse uptake only, without discrete areas of focal disease. Figures 1 and 2 are dedicated PET studies showing patients with both diffuse and focal disease with no prior therapy.

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FIGURE 1.

Patient with IgA λ-chain myeloma, stage IIIA. Radiographs revealed multiple lytic lesions in areas that showed positive findings on ¹⁸F-FDG PET imaging (e.g., spine, pelvis, and hips). Plasmacytoma in left lung was confirmed on biopsy. Plasmacytomas were noted in left apex and hilar regions on CT scanning. Splenic myeloma was also suspected but not directly confirmed.

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FIGURE 2.

Patient with Bence Jones protein λ-chain myeloma. Extensive disease is seen in spine, and plasmacytomas are seen in right lower lung and left upper abdomen.

Of particular interest, 4 (25%) of 16 patients had no evidence of multiple myeloma on a routine skeletal bone survey but had positive whole-body ¹⁸F-FDG PET findings. One patient previously considered to have stage IA disease was reconsidered to have a single (solitary) plasmacytoma. Dedicated PET showed the patient to have multiple lesions, which were subsequently confirmed by MRI and CT. The disease of this patient was restaged as IIIA. The 3 additional patients had stage III disease by other criteria but had no documented sites of discrete or focal bone disease. Again, the new sites of disease were confirmed by MRI or CT.

There were also 4 (25%) of 16 patients, already documented to have stage III disease, who were found to have additional foci of extramedullary disease. The nature of the focal uptake was confirmed both by other imaging and by direct biopsy in 2 instances (pulmonary [Fig. 1] and periorbital). The predilection for extramedullary spread was also confirmed by the subsequent development of additional extramedullary disease, including subcutaneous lesions. One patient died with fulminant disease at 4 mo after the study, and another with aggressive relapse after stem cell transplantation died at 23 mo. The other 2 patients with extramedullary disease are still alive and undergoing therapy at 6 and 18 mo, although the disease of 1 has already relapsed after transplantation.

MGUS

Fourteen patients had a working diagnosis of MGUS (13) and negative scan findings, showing neither diffuse marrow uptake nor areas of focal disease in marrow sites. Current follow-up is between 3 and 43+ mo from the time of the first ¹⁸F-FDG PET scan. All but 2 patients had a new diagnosis of MGUS. The 2 prior diagnoses were of 3 and 9 y duration. Both patients have negative scan findings and still have MGUS 23 and 31 mo later. In 1 (7%) of 14 patients, multiple myeloma has since developed after 8 mo and was associated with the development of multifocal positive scan findings. Of interest, 4 patients have been documented to have primary systemic amyloidosis in association with the MGUS in the absence of myeloma. At the time of the first study, all sites of amyloid were also negative on scans. However, in 1 patient, treated with stem cell transplantation for amyloidosis, focal uptake at the site of a plasmacytoma subsequently developed, with amyloid located in the distal esophagus (Fig. 3). This solitary relapse site has been treated with local irradiation. One other patient with IgA κ-chain MGUS had an ¹⁸F-FDG PET scan that was negative at bone marrow sites but revealed a renal mass. This proved to be a renal carcinoma (previously unsuspected), which was resected and has not recurred at more than 2 y later. The whole-body ¹⁸F-FDG PET scan remains negative in bone marrow sites, and the IgA κ-chain MGUS is persistent but stable.

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FIGURE 3.

Patient with relapse after stem cell transplantation. Dysphagia developed and was associated with positive finding in distal esophagus. Direct biopsy showed plasma cells with local amyloid deposition. This responded well to local irradiation.

Remission Monitoring

Ten patients have been monitored with baseline and follow-up ¹⁸F-FDG PET scans for 6–42+ mo. New focal sites of disease have developed in 6 (60%) of the 10 patients. Because patients with nonsecretory disease were preferentially enrolled for monitoring in this initial study of whole-body ¹⁸F-FDG PET, the establishment of specific sites of focal relapse was especially helpful for this subset of patients. In all 6 instances of focal relapse, local irradiation was feasible and used as a first step in management. Four (67%) of 6 had nonsecretory disease and no other methodology available to adequately screen the whole skeleton for early relapse.

Relapsing Disease

Twenty-six patients were evaluated at the time of suspected relapse. Twenty-one (81%) of the 26 patients had new, previously unsuspected sites of disease documented by whole-body scanning. This was extremely helpful in assessing the extent and exact anatomic distribution of the disease. Six (23%) of the 26 patients showed evidence of new extramedullary disease, which was subsequently documented by other imaging and biopsy plus further follow-up. Extramedullary sites included skin, bladder, retroperitoneum (with ureteral obstruction), liver, lung (Fig. 2), and mediastinum. As noted for the previously untreated patients, the onset of extramedullary disease indicated a poor prognosis. Currently, subsequent survival has been 3, 4, 6+, 8, 11, and 13+ months: that is, a median of 7 mo.

For the patients showing relapse in bone, the new sites of disease were widely scattered and typical for myeloma; including the spine, scapulae, ribs, clavicle, base of the skull, pelvis, and femora. The whole-body ¹⁸F-FDG PET scans showed new sites of active disease. Again, in patients with nonsecretory disease, studied for the first time at relapse, focal disease was amenable to radiation in 2 additional instances. When necessary, sites of disease were confirmed by bone marrow or tissue biopsy, MRI, or CT, especially around joints such as the shoulder to exclude inflammatory disease.

Impact of Dedicated ¹⁸F-FDG PET

The dedicated ¹⁸F-FDG PET system has been in use at Cedars-Sinai Medical Center since September 1999. Approximately one third of the scans performed as part of this study used this system and involved 50% of the patients. The dedicated system significantly improved the quality of the images. However, serial studies involving earlier coincidence or collimated studies did not affect the serial follow-up conclusions (Table 2) or the algorithm for further evaluation (Table 3). For example, the patient in whom myeloma developed at 8 mo (Table 2) underwent initial scanning with the coincidence technique. The findings were negative, and the patient was clinically stable. At the time of follow-up with the dedicated system, new changes reflective of myeloma were seen and showed a correlation with other changes in the laboratory results and clinical status. It is obvious that the dedicated system has superior resolution and should be used whenever possible to maximize the data.