EVALUATION OF BONE DISEASE

 

 

PET

Positron emission tomography with 2-deoxy-2-[18]fluoro-D-glucose (FDG-PET) imaging is useful in MM because:
 - It provides a whole body image
 - It shows sites of occult disease
 - It is of particular value in patients with non-secretory myeloma
 - It is of particular value in patients with solitary plasmacytoma

Bone lesions should be at least 5-10 mm in size to be visualized at PET.

While x-rays are unable to differentiate between old and inactive bone lesions and new lesions, the PET scan shows only active myeloma lesions. This is particularly useful when evaluating treatment response.

PET/CT is better than MRI in determining the remission status, because inactive lesions may persist and lead to a false-positive MRI.

The following picture shows numerous bone lesions with active metabolic uptake at the FDG-PET scan (my personal archive):

 

 

The PET scan is an excellent test to monitor response to therapy, as lesions seen at X-rays and MRI may persist indefinitely, even with persistent remission of the disease, while PET scan shows only areas of active disease. The following picture shows numerous bone lesions in the bones of a patient with multiple myeloma before and after a single course of chemotherapy, documenting disease response (my personal archive):

 

 

 

PET scan may be combined with CT scan. The following PET/CT scan shows multiple areas of active metabolic uptake by the bone lesions in multiple myeloma (my personal archive):

 

 

In the following picture, the PET/CT scan easily identifies the area of active metabolic uptake in the thoracic spine in a patient with multiple myeloma (my personal archive):

 

 

The PET/CT scan is an excellent imaging test to document extramedullary disease, as seen in the following picture, taken from a patient with multiple myeloma involving the pancreas (my personal archive):

 

 

 

 

FDG PET or PET/CT for Detecting Intramedullary and Extramedullary Lesions in Multiple Myeloma: A Systematic Review and Meta-analysis.
Clin Nucl Med. 2012 Sep;37(9):833-7.
Lu YY, Chen JH, Lin WY, Liang JA, Wang HY, Tsai SC, Kao CH.
[Review]
This is a review of 14 studies with 395 patients with multiple myeloma.
The pooled estimates of sensitivity of PET were: 61% for intramedullary lesions and 96% for extramedullary lesions.
The pooled estimates of specificity of PET were: 94% for intramedullary lesions and 78% for extramedullary lesions.

 

 

Initial results in the assessment of multiple myeloma using 18F-FDG PET.
Eur J Nucl Med Mol Imaging. 2002 Mar;29(3):361-6.
Schirrmeister H, Bommer M, Buck AK, Müller S, Messer P, Bunjes D, Döhner H, Bergmann L, Reske SN.
This study investigated the appearance of bone lesions on FDG-PET in 28 patients with multiple myeloma and 15 patients with solitary plasmacytoma, and related the findings to those of radiographs, MRI, and CT. Focally increased tracer uptake was observed in 38 of 41 (93%) osteolytic bone lesions in 23 patients. In addition, 71 additional bone lesions were detected in 14 patients with negative radiographs. Findings at FDG-PET influenced clinical management in 5 (14%) patients. FDG-PET proved highly accurate in detecting multiple myeloma, and it revealed a greater extent of disease than routine radiographs in 14 of 23 (61%) patients with lytic bone lesions. FDG-PET is useful in the initial staging of solitary plasmacytoma.

Fluoro-deoxyglucose positron emission tomography imaging for the detection of occult disease in multiple myeloma.
Br J Haematol. 2002 Apr;117(1):133-5.
Orchard K, Barrington S, Buscombe J, Hilson A, Prentice HG, Mehta A.

Whole-body (18)F-FDG PET identifies high-risk myeloma.
J Nucl Med. 2002 Nov;43(11):1457-63.
Durie BG, Waxman AD, D'Agnolo A, Williams CM.
This study evaluated the clinical utility of whole-body PET with (18)F-FDG in 52 patients with multiple myeloma at various disease stages and 14 patients with MGUS, and it compared the results with routine clinical and staging information, including CT and MRI scans. Negative PET reliably predicted MGUS. All 16 untreated patients with active myeloma had focal or diffusely positive PET scan findings, and 4 (25%) of them had positive PET and negative radiologic skeletal surveys. Another 4 (25%) of those 16 patients had focal extramedullary disease evident at PET. Extramedullary disease was also detected at PET in 6 of 26 (23%) patients with MM in relapse. Persistent positive PET after induction therapy predicted early relapse. PET was particularly helpful in identifying focal recurrent disease in patients with nonsecretory or hyposecretory disease.

Diagnostic utility of FDG PET in multiple myeloma.
Skeletal Radiol. 2002 Dec;31(12):690-4.
Jadvar H, Conti PS.
In this study, PET scans showed development of new lesions or higher lesion glucose uptake in patients with progressive disease, while the other imaging studies showed no significant interval changes. Therefore, PET is very useful in assessing the extent of active disease and in evaluating treatment response.

Value of FDG PET in the assessment of patients with multiple myeloma.
AJR Am J Roentgenol. 2005 Apr; 184(4):1199-204.
Bredella MA, Steinbach L, Caputo G, Segall G, Hawkins R.
In this study of 17 FDG PET scans in 13 MM patients, sensitivity of FDG PET in detecting myelomatous involvement was 85% and specificity was 92%.

Role of 18F-FDG PET/CT in the assessment of bone involvement in newly diagnosed multiple myeloma: preliminary results.
Eur J Nucl Med Mol Imaging. 2006 May;33(5):525-31.
Nanni C, Zamagni E, Farsad M, Castellucci P, Tosi P, Cangini D, Salizzoni E, Canini R, Cavo M, Fanti S.
In this study, (18)F-FDG PET/CT detected more lesions in 16 of 28 (57%) MM patients. Of these 16 patients, 9 had a completely negative skeletal survey. In 12 of 28 43%) patients, the two methods yielded equivalent findings. When comparing (18)F-FDG PET/CT and MRI, 7 of 28 (25%) patients were found to have more lytic bone lesions, all of which were located outside the field included in the MRI. In 7 of 28 (25%) patients, skeletal MRI detected an infiltrative pattern in the spine whereas the (18)F-FDG PET/CT was negative. In conclusion, PET scans are more sensitive than skeletal survey in detecting lytic bone lesions, and skeletal MRI may be superior to PET in diagnosing an infiltrative pattern in the spine. MM bone disease should be evaluated with both MRI of the spine and PET/CT.

18F-FDG PET/CT, 99mTc-MIBI, and MRI in evaluation of patients with multiple myeloma.
J Nucl Med. 2008 Feb;49(2):195-200.
Fonti R, Salvatore B, Quarantelli M, Sirignano C, Segreto S, Petruzziello F, Catalano L, Liuzzi R, Rotoli B, Del Vecchio S, Pace L, Salvatore M.
This is a prospective study comparing imaging findings in 33 newly diagnosed patients with MM, who underwent whole-body (18)F-FDG PET/CT, whole-body (99m)Tc-MIBI, and MRI of the spine and pelvis within 10 days.
 - FDG PET/CT was positive in 32 patients (16 with focal uptake, 3 with diffuse uptake, and 13 with both focal and diffuse uptake)
   Total: 196 focal lesions (178 in bones and 18 in soft tissues), of which 121 in areas other than the spine and pelvis
 - (99m)Tc-MIBI was positive in 30 patients (6 focal, 11 diffuse, 13 focal and diffuse uptake)
   Total: 63 focal lesions (60 in bones and 3 in soft tissues), of which 53 in areas other than the spine and pelvis
 - MRI of the spine and pelvis was positive in 27 patients (6 focal, 13 diffuse, 8 focal and diffuse uptake)
   Total: 51 focal lesions (40 in spine and 11 in pelvis)
PET/CT performed better than (99m)Tc-MIBI in the detection of focal lesions, whereas (99m)Tc-MIBI was superior in the visualization of diffuse disease. In the spine and pelvis, MRI was comparable to FDG PET/CT and (99m)Tc-MIBI. Since myelomatous lesions often develop out of spinal and pelvic areas, MRI should be reserved to the evaluation of bone marrow involvement of these regions.

F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma.
Blood. 2009 Sep 3;114(10):2068-76.
Bartel TB, Haessler J, Brown TL, Shaughnessy JD Jr, van Rhee F, Anaissie E, Alpe T, Angtuaco E, Walker R, Epstein J, Crowley J, Barlogie B.
This study evaluates the use of PET scans in 239 patients with newly diagnosed myeloma. The presence of >3 active focal lesions was associated with inferior prognosis, including overall survival. Normalization of the PET scan before the first stem cell transplant was associated with better prognosis.

Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation.
Blood. 2011 Dec 1;118(23):5989-95.
Zamagni E, Patriarca F, Nanni C, Zannetti B, Englaro E, Pezzi A, Tacchetti P, Buttignol S, Perrone G, Brioli A, Pantani L, Terragna C, Carobolante F, Baccarani M, Fanin R, Fanti S, Cavo M.
This study analyzed the prognostic relevance of PET in 192 patients with multiple myeloma. At multivariate analysis, independent variables for poor prognosis were:
  - SUV >4.2 at baseline (46%)
  - EMD at baseline (6%)
  - Persistent uptake after autologous stem cell transplant (35%)

 

FALSE-NEGATIVE PET

Low expression of hexokinase-2 is associated with false-negative FDG-positron emission tomography in multiple myeloma.
Blood. 2017 Jul 6;130(1):30-34.
Rasche L, Angtuaco E, McDonald JE, Buros A, Stein C, Pawlyn C, Thanendrarajan S, Schinke C, Samant R, Yaccoby S, Walker BA, Epstein J, Zangari M, van Rhee F, Meissner T, Goldschmidt H, Hemminki K, Houlston R, Barlogie B, Davies FE, Morgan GJ, Weinhold N.
Among 227 patients with newly diagnosed multiple myeloma, the rate of false-negative FDG-PET was 11%. Interestingly, the false-negativity was not correlated to the tumor load (as represented by percentage of plasma cells infiltrating the bone marrow, or the plasma cell proliferation rate), but it was found to be associated with low expression of hexokinase-2, an enzyme involved in the glycolysis. This would explain the low uptake of fluorodeoxyglucose by the malignant cells.

 

 


PET/MRI

 

Comparison of (18)F-FDG PET/CT and PET/MRI in patients with multiple myeloma.
Am J Nucl Med Mol Imaging. 2015 Oct 12;5(5):469-78.
Sachpekidis C, Hillengass J, Goldschmidt H, Mosebach J, Pan L, Schlemmer HP, Haberkorn U, Dimitrakopoulou-Strauss A.

 

 


Giampaolo Talamo, M.D.