Eric C Ehman1, M Samir El-Sady1, Marie F Kijewski1, Yiu Ming Khor1, Sophia Jacob1, Frederick L Ruberg2, Vaishali Sanchorawala2, Heather Landau3, Andrew J Yee4, Giada Bianchi5, Marcelo F Di Carli1,6, Rodney H Falk7, Hyewon Hyun1, Sharmila Dorbala8,6,7. 1. Division of Nuclear Medicine, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. 2. Amyloidosis Center, Boston University School of Medicine, Boston, Massachusetts. 3. Division of Medical Oncology, Memorial Sloan Kettering Medical Center, New York, New York. 4. Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 5. Division of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts. 6. CV Imaging Program, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts; and. 7. Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 8. Division of Nuclear Medicine, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts sdorbala@bwh.harvard.edu.
Abstract
Immunoglobulin light-chain (AL) amyloidosis affects multiple systemic organs. However, determination of the precise extent of organ involvement remains challenging. Targeted amyloid imaging with 18F-florbetapir PET/CT offers the potential to detect AL deposits in multiple organs. The primary aim of this study was to determine the distribution and frequency of AL deposits in the various organs of subjects with systemic AL amyloidosis using 18F-florbetapir PET/CT. Methods: This prospective study included 40 subjects with biopsy-proven AL amyloidosis including active AL amyloidosis (n = 30) or AL amyloidosis in hematologic remission for more than 1 y (n = 10). All subjects underwent 18F-florbetapir PET/CT, skull base to below the kidney scan field, from 60 to 90 min after injection of radiotracer. Volume-of-interest measurements of SUVmax were obtained using Hermes software for the parotid gland, tongue, thyroid, lung, gastric wall, pancreas, spleen, kidney, muscle, abdominal fat, lower thoracic spine, vertebral body, and humeral head. Uptake in each organ was visually compared with that in spine bone marrow. An SUVmax of at least 2.5 was considered abnormal in all organs other than the liver. Results: Compared with the international consensus definition of organ involvement, 18F-florbetapir PET/CT identified amyloid deposits in substantially higher percentages of subjects for several organ systems, including parotid gland (50% vs. 3%), tongue (53% vs. 10%), and lung (35% vs. 10%). In several organ systems, including kidney (13% vs. 28%) and abdominal wall fat (10% vs. 13%), PET identified involvement in fewer subjects than did international consensus. Quantitative analysis of 18F-florbetapir PET/CT revealed more frequent organ involvement than did visual analysis in the tongue, thyroid, lung, pancreas, kidney, muscle, and humeral head. Extensive organ amyloid deposits were observed in active AL as well as in AL remission cohorts, and in both cardiac and noncardiac AL cohorts. Conclusion: 18F-florbetapir PET/CT detected widespread organ amyloid deposition in subjects with both active AL and AL hematologic remission. In most instances, amyloid deposits in the various organs were not associated with clinical symptoms and, thus, were unrecognized. Early recognition of systemic organ involvement may help tailor treatment, and noninvasive monitoring of organ-level disease may guide management with novel fibril-resorbing therapies.
Immunoglobulin light-chain (AL) amyloidosis affects multiple systemic organs. However, determination of the precise extent of organ involvement remains challenging. Targeted amyloid imaging with 18F-florbetapir PET/CT offers the potential to detect AL deposits in multiple organs. The primary aim of this study was to determine the distribution and frequency of AL deposits in the various organs of subjects with systemic AL amyloidosis using 18F-florbetapir PET/CT. Methods: This prospective study included 40 subjects with biopsy-proven AL amyloidosis including active AL amyloidosis (n = 30) or AL amyloidosis in hematologic remission for more than 1 y (n = 10). All subjects underwent 18F-florbetapir PET/CT, skull base to below the kidney scan field, from 60 to 90 min after injection of radiotracer. Volume-of-interest measurements of SUVmax were obtained using Hermes software for the parotid gland, tongue, thyroid, lung, gastric wall, pancreas, spleen, kidney, muscle, abdominal fat, lower thoracic spine, vertebral body, and humeral head. Uptake in each organ was visually compared with that in spine bone marrow. An SUVmax of at least 2.5 was considered abnormal in all organs other than the liver. Results: Compared with the international consensus definition of organ involvement, 18F-florbetapir PET/CT identified amyloid deposits in substantially higher percentages of subjects for several organ systems, including parotid gland (50% vs. 3%), tongue (53% vs. 10%), and lung (35% vs. 10%). In several organ systems, including kidney (13% vs. 28%) and abdominal wall fat (10% vs. 13%), PET identified involvement in fewer subjects than did international consensus. Quantitative analysis of 18F-florbetapir PET/CT revealed more frequent organ involvement than did visual analysis in the tongue, thyroid, lung, pancreas, kidney, muscle, and humeral head. Extensive organ amyloid deposits were observed in active AL as well as in AL remission cohorts, and in both cardiac and noncardiac AL cohorts. Conclusion:18F-florbetapir PET/CT detected widespread organ amyloid deposition in subjects with both active AL and AL hematologic remission. In most instances, amyloid deposits in the various organs were not associated with clinical symptoms and, thus, were unrecognized. Early recognition of systemic organ involvement may help tailor treatment, and noninvasive monitoring of organ-level disease may guide management with novel fibril-resorbing therapies.
Authors: Vittorio Bellotti; Mario Nuvolone; Sofia Giorgetti; Laura Obici; Giovanni Palladini; Paola Russo; Francesca Lavatelli; Vittorio Perfetti; Giampaolo Merlini Journal: Ann Med Date: 2007 Impact factor: 4.709
Authors: Giampaolo Merlini; Raymond L Comenzo; David C Seldin; Ashutosh Wechalekar; Morie A Gertz Journal: Expert Rev Hematol Date: 2013-12-18 Impact factor: 2.929
Authors: Maria Teresa Cibeira; Vaishali Sanchorawala; David C Seldin; Karen Quillen; John L Berk; Laura M Dember; Adam Segal; Frederick Ruberg; Hans Meier-Ewert; Nancy T Andrea; J Mark Sloan; Kathleen T Finn; Gheorghe Doros; Joan Blade; Martha Skinner Journal: Blood Date: 2011-08-09 Impact factor: 22.113
Authors: Tricia R Andrews; Gerardo Colon-Otero; Kenneth T Calamia; David M Menke; Kevin B Boylan; Robert A Kyle Journal: Mayo Clin Proc Date: 2002-12 Impact factor: 7.616
Authors: Morie A Gertz; Ray Comenzo; Rodney H Falk; Jean Paul Fermand; Bouke P Hazenberg; Philip N Hawkins; Giampaolo Merlini; Philippe Moreau; Pierre Ronco; Vaishali Sanchorawala; Orhan Sezer; Alan Solomon; Giles Grateau Journal: Am J Hematol Date: 2005-08 Impact factor: 10.047
Authors: Shaji K Kumar; Morie A Gertz; Martha Q Lacy; David Dingli; Suzanne R Hayman; Francis K Buadi; Kristen Short-Detweiler; Steven R Zeldenrust; Nelson Leung; Philip R Greipp; John A Lust; Stephen J Russell; Robert A Kyle; S Vincent Rajkumar; Angela Dispenzieri Journal: Mayo Clin Proc Date: 2011-01 Impact factor: 7.616
Authors: Christopher M Clark; Julie A Schneider; Barry J Bedell; Thomas G Beach; Warren B Bilker; Mark A Mintun; Michael J Pontecorvo; Franz Hefti; Alan P Carpenter; Matthew L Flitter; Michael J Krautkramer; Hank F Kung; R Edward Coleman; P Murali Doraiswamy; Adam S Fleisher; Marwan N Sabbagh; Carl H Sadowsky; Eric P Reiman; P Eric M Reiman; Simone P Zehntner; Daniel M Skovronsky Journal: JAMA Date: 2011-01-19 Impact factor: 56.272
Authors: Abhinay D Joshi; Michael J Pontecorvo; Lee Adler; Michael G Stabin; Daniel M Skovronsky; Alan P Carpenter; Mark A Mintun Journal: EJNMMI Res Date: 2014-01-08 Impact factor: 3.138
Authors: Rudolf A Werner; James T Thackeray; Johanna Diekmann; Desiree Weiberg; Johann Bauersachs; Frank M Bengel Journal: J Nucl Med Date: 2020-04-17 Impact factor: 11.082
Authors: Riemer H J A Slart; Andor W J M Glaudemans; Olivier Gheysens; Mark Lubberink; Tanja Kero; Marc R Dweck; Gilbert Habib; Oliver Gaemperli; Antti Saraste; Alessia Gimelli; Panagiotis Georgoulias; Hein J Verberne; Jan Bucerius; Christoph Rischpler; Fabien Hyafil; Paola A Erba Journal: Eur Heart J Cardiovasc Imaging Date: 2020-12-01 Impact factor: 6.875
Authors: Riemer H J A Slart; Andor W J M Glaudemans; Olivier Gheysens; Mark Lubberink; Tanja Kero; Marc R Dweck; Gilbert Habib; Oliver Gaemperli; Antti Saraste; Alessia Gimelli; Panagiotis Georgoulias; Hein J Verberne; Jan Bucerius; Christoph Rischpler; Fabien Hyafil; Paola A Erba Journal: Eur J Nucl Med Mol Imaging Date: 2020-10-27 Impact factor: 9.236