Fluorine-18 labeled fluorodeoxyglucose PET useful ...

http://informahealthcare.com/amy ISSN: 1350-6129 (print), 1744-2818 (electronic) Amyloid, 2013; 20(2): 135–137 ! 2013 Informa UK Ltd. DOI: 10.3109/13506129.2013.773888

LETTER TO THE EDITOR

Fluorine-18 labeled fluorodeoxyglucose PET useful for therapy monitoring in localized AL amyloidosis? Walter Noordzij1, Andor W. J. M. Glaudemans1, Rudi A. Dierckx1, Riemer H. J. A. Slart1, Alexander L. Boerboom2, and Bouke P. C. Hazenberg3 Department of Nuclear Medicine and Molecular Imaging, 2Department of Orthopaedic Surgery, and 3Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Localized amyloidosis is restricted to one particular organ or tissue and can often be found in specific sites of the body, such as the eyelid, joint, cardiac atria, larynx, ureter and skin. A common form of localized amyloidosis is caused by foci of otherwise benign monoclonal B lymphocytes or plasma cells producing an excess of immunoglobulin free lambda or kappa light chains that are deposited as AL amyloid [1]. Localized AL amyloidosis differs from systemic AL amyloidosis by the local presence of clonal plasma cells and giant cells and by the local production of amyloid [2]. Serum levels of free lambda and kappa amyloid precursor proteins are useful for treatment monitoring of systemic AL amyloidosis, in combination with monitoring the process of amyloid accumulation through organ function tests (N-terminus pro-brain natriuretic peptide, troponin, serum albumin, alkaline phosphatase and creatinine clearance) and organ characteristics, such as echocardiography and iodine-123 labeled serum amyloid P component (123I-SAP) scintigraphy [3,4]. Monitoring the effect of treatment in localized amyloidosis is usually limited to occasional inspection of the local situation. Inspection is often sufficient, but sometimes inadequate and in these cases it would be advantageous to have disposal of an easily accessible tracer and diagnostic modality. Fluorine-18 labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) is a worldwide available imaging technique which has potential in amyloidosis. In this report, we propose the potential use of 18F-FDG PET for treatment monitoring of localized AL amyloidosis, illustrated by a patient with such a disease. Patient A (a 63-year-old male) was referred to our amyloid referral centre because of localized AL amyloidosis in his left ankle joint. His medical history mentioned psoriasis, diagnosed 47 years ago. Twenty-eight years later, he was treated for probable psoriatic arthritis with chronic nonresolving synovitis and secondary osteoarthritis of his left ankle.

Address for correspondence: Walter Noordzij, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. Tel: 0031 50 361 61 61. Fax: 0031 50 361 16 87. E-mail: [email protected]

An anterolateral synovectomy of the ankle was performed with only little symptomatic effect. Pain, instability and local warmth did not resolve after surgery and even increased. Orthopedic analysis, including conventional radiography and bone scintigraphy, showed chronic inflammation of the left ankle joint. A biopsy of synovial tissue showed amorphous eosinophil deposits with infiltrating leukocytes, lymphocytes, plasma cells and giant cells. The deposits turned out to be positive for Congo red staining and showed negative immunostaining for AA and transthyretin with non-conclusive staining for kappa and lambda light chains. The plasma cells did not show restriction for kappa or lambda light chain. The most probable diagnosis was an AL amyloidoma of the ankle. In retrospect, biopsies at the time of the anterolateral synovectomy 19 years ago, at that time it already showed similar amyloid deposits. Bone marrow aspiration of the iliac crest showed normal cell lines and normal hematopoiesis, without amyloid deposition or signs of a clonal plasma cell dyscrasia. Also, revealed a long history of dry cough and professional asbestos exposure 30 years in the past, for which he underwent highresolution-computed tomography of the thorax. Only pleural calcifications turned out to be present, especially positioned on the diaphragm. 123I-SAP scintigraphy was positive for amyloid deposition in the left ankle and showed otherwise no specific organ uptake. 18F-FDG PET/CT (Figure 1A) also showed high tracer uptake at the ankle joint. The patient was referred to the department of orthopedic surgery for additional anterolateral and posteromedial synovectomy and debulking of the amyloidoma. Amyloid depositions were encountered directly in the subcutaneous layers with abundant extra-articular and intra-articular manifestations. Histological analysis confirmed the diagnosis of amyloidosis and inflammation, showed this time a slight excess of lambda light chain-restricted plasma cells, as well as one (or possibly two) clonal B-cell/plasma cell populations using heavy-chain PCR analysis. Despite the rather low specificity, these findings further supported our initial diagnosis of an AL amyloidoma. Abdominal subcutaneous adipose tissue aspiration did not reveal any deposits of amyloid.

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Figure 1. 18F-FDG PET/CT before (A) and after (B) therapeutic synovectomy, showing decreasing uptake at the site of the left ankle joint. Standardized uptake value (SUVmax) decreased from 2.7 to 2.1. Physiological uptake in the brain, salivary glands, left ventricle, kidneys, urine bladder and arm and finger muscles. Infusion artefacts on the right arm (B).

Figure 2. 123I SAP scintigraphy after therapeutic synovectomy showing elevated uptake at the right ankle joint (arrow). The uptake was at the right ankle joint lower than before the therapeutic synovectomy (10.337 counts versus 25.934 counts, in a corresponding region of interest). Normal uptake at the liver, spleen and mediastinum. Physiological uptake in the nasal mucosa, thyroid gland and urinary tract.

Recovery was arduous, with slow wound healing and pain. One year after the therapeutic synovectomy, the pain increased again and his action radius decreased further. 123 I SAP scintigraphy (Figure 2) and 18F-FDG PET/CT (Figure 1B) were repeated and both modalities showed decreasing uptake at the site of the left ankle joint, both visually and semi-quantitatively. The absolute count number decreased in a corresponding region-of-interest on both 123 I-SAP scintigraphies (10.337 after versus 25.934 before the therapeutic synovectomy). Standardized uptake value (SUVmax) on the 18F-FDG PET/CT scan, a measure of metabolic uptake (calculated according to European guidelines [5]) decreased from 2.7 to 2.1. Additional magnetic resonance imaging of the left ankle joint showed erosions of the talocrural joint with extensive intra-articular fluid collections. Conventional radiographs of the left ankle showed progression of degenerative changes in the talocrural joint. These findings were interpreted as secondary damage of the talocrural joint due to longstanding amyloid deposition, inflammation, synovectomies and debulking of the amyloidoma. The most probable causes of the pain were damage of the joint in combination with some remnants of the amyloidoma. No signs of progression of the amyloidoma were found. Currently, the best validated imaging modality for diagnosis and evaluation of treatment effect in amyloidosis is the 123 I-SAP-scintigraphy [4]. One of the main limitations is its restricted availability of the tracer. 18F-FDG PET/CT is a

well-established imaging modality, especially for oncologic cases, but is also used in many infectious and inflammatory diseases [6]. There is an increasing interest in its use in amyloidosis. Several case reports suggest the use of 18F-FDG PET/CT in amyloidosis; however, case series are scarce. In a recent study, 10 patients with biopsy-proven AL amyloidosis underwent 18F-FDG PET/CT [7]. Seven of these patients showed focal elevated FDG uptake, corresponding with sites of amyloid deposits. Median standardized uptake value (neither according to NEDPAS nor corrected for blood glucose level) was 6.5 (range 4–15). The authors concluded that the FDG uptake of the lesions may be related to AL amyloidosis in untreated patients. Recently, our group showed that FDG-PET may be useful to distinguish systemic amyloidosis from localized amyloidosis [8]. Ten of 11 patients with localized amyloidosis showed increased FDG uptake at the amyloid site, whereas none of all 10 patients with systemic amyloidosis showed any elevated uptake at all. In localized amyloidosis, we suppose that the high uptake of FDG is due to surrounding giant cells and other immunoreactive cells (macrophages, monocytes and leucocytes). This is in agreement with the earlier mentioned hypothesis of Westermark [2]. 18 F-FDG PET is also used for therapy monitoring in many oncological and infectious diseases. It is rather low specificity for the initial differentiation between primary and secondary inflammation due to surgical interventions (for example), can be a major limitation. For example, the uptake of 18F-FDG

DOI: 10.3109/13506129.2013.773888

along prosthetic implants can be reactive up to several years after placement [9]. The role of 18F-FDG PET in the evaluation of treatment of localized amyloidosis has not been reported before. We hypothesize that if uptake is high in localized amyloidosis, this imaging modality may be useful for monitoring the effect of treatment. Since at this moment its place in the primary work-up of localized AL amyloidosis is not yet established, this hypothesis should be considered as an undetermined future perspective. Both aspects of FDGPET, i.e. diagnosis and therapy effect monitoring, should be addressed in future studies.

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F-FDG PET/CT may be an interesting and widely available tool for evaluation of therapy effect in patients with localized AL amyloidosis. Currently, the exact role is only speculative. Future studies are needed to assess the place of this nuclear medicine imaging modality for this indication.

Declaration of interest The authors report no conflicts of interest.

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