Early Detection of Multiorgan Light-Chain Amyloidosis by Whole-Body 18F-Florbetapir PET/CT

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 SUV_max 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 SUV_max 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.

Keywords: 18F-florbetapir; AL; PET/CT; organ; systemic light chain amyloidosis.

FIGURE 1.

Detection of organ involvement by ¹⁸F-florbetapir uptake. Distribution of SUV_max values is shown for each organ. Each marker corresponds to single subject. Dotted line indicates assigned threshold of 2.5 SUV_max between normal and abnormal. Hum. = humeral.

FIGURE 2.

Proportion of subjects demonstrating ¹⁸F-florbetapir uptake by organ. Visual involvement was defined as uptake greater than bone marrow. Quantitative assessment was deemed positive if SUV_max for volume of interest within organ was ≥ 2.5. Vertebral body uptake was visual reference; therefore, subjective assessment of abnormal bone marrow uptake was not possible.

FIGURE 3.

Normal ¹⁸F-florbetapir biodistribution. PET maximum-intensity projection image shows ¹⁸F-florbetapir distribution in healthy volunteer. (Reprinted with permission of (14).)

FIGURE 4.

Images from 2 subjects with biopsy-proven active systemic AL amyloidosis. (A) Maximum-intensity projection image from ¹⁸F-florbetapir PET/CT shows abnormal uptake in tongue and lungs. (B–D) Axial fused PET/CT images confirm diffuse abnormal uptake throughout tongue (B), parotids and thyroid (C), and both lungs (D). CT appearance of lungs was unremarkable other than mild atelectasis. (E–G) Abnormal uptake (*) is also seen in kidneys (E) and spleen (F and G).

FIGURE 5.

A 55-y-old man with cardiac AL amyloidosis but in AL remission for more than 1 y. (A) Coronal fusion ¹⁸F-florbetapir PET/CT image shows abnormal uptake in lungs. (B and C) Axial fusion images show abnormal uptake in submandibular glands (B) and thyroid (C). This patient also had abnormal uptake in parotids and tongue (not pictured).