New agents for scintigraphy in rheumatoid arthritis

Radiopharmaceuticals have been used as investigative tools for the detection and treatment of arthritis activity in rheumatoid arthritis (RA) since the 1950s. Against the background of the pathophysiology of RA, the current status of joint scintigraphy and possible future developments are reviewed. Both non-specific (radiolabelled leucocytes and technetium-99m labelled human immunoglobulin) and specific targeting radiopharmaceuticals (including radiolabelled antibodies) are considered. The use of radiopharmaceuticals in the detection of arthritis activity has the advantages of allowing direct imaging of joints by means of whole-body scintigraphy and of joints that are difficult to assess clinically or radiographically. Promising results have been obtained with radiolabelled anti-CD4 and anti-E-selectin antibodies and with somatostatin receptor imaging, but more data are available regarding^99mTc-IgG scintigraphy, which differentiates between the various degrees of arthritis activity and thus facilitates the choice of antirheumatic drug. Newer promising approaches to the imaging of RA include the use of radiolabelled J001 and cytokines, though studies on these are limited at present.     

Somatostatin receptor scintigraphy and gallium scintigraphy in patients with sarcoidosis.

Somatostatin receptor scintigraphy (SRS) has been shown to reveal sarcoidosis sites. The aim of this study was to prospectively compare SRS and gallium scintigraphy in the evaluation of pulmonary and extrapulmonary involvement in patients with proven sarcoidosis. METHODS: Eighteen patients with biopsy-proven sarcoidosis were included. Nine were or recently had been receiving steroid therapy at the time of the examination. Planar gallium scintigraphy (head, chest, abdomen, and pelvis) and thoracic SPECT were performed at 48-72 h after injection of a mean dose of 138 +/- 21 MBq 67Ga. Planar SRS and thoracic SPECT were performed at 4 and 24 h after injection of a mean dose of 148 +/- 17 MBq 111n-pentetreotide. RESULTS: Gallium scintigraphy found abnormalities in 16 of 18 patients (89%) and detected 64 of 99 clinically involved sites (65%). SRS found abnormalities in 18 of 18 patients and detected 82 of 99 clinically involved sites (83%). Of the 9 treated patients, gallium scintigraphy found abnormalities in 7 (78%), detecting 23 of 39 clinically involved sites (59%), whereas SRS found abnormalities in 9, detecting 32 of 39 clinically involved sites (82%). CONCLUSION: This study suggests that, compared with gallium scintigraphy, SRS appears to be accurate and contributes to a better evaluation of organ involvement in sarcoidosis patients, especially those treated with corticosteroids.     

Indium-111 octreotide scintigraphy in neurofibromatosis

Scintigraphy with the radiolabelled somatostatin analogue indium-111-DTPA-D-Phe-l-octreotide has recently been proposed for the imaging of CNS neoplasms expressing somatostatin receptors. While meningiomas are imaged with high sensitivity, neurinomas do not take up octreotide owing to the lack of somatostatin receptors. Neurofibromatosis is a relatively uncommon disorder in which meningiomas and neurinomas often occur in the same patient. Differential diagnosis between these two tumours by computed tomography and magnetic resonance imaging can be difficult. This study reports on^{1 11}In-octreotide scintigraphy in four patients with neurofibromatosis.¹¹In-octreotide scintigraphy was shown to be very helpful in the in vivo differential diagnosis: all four meningiomas showed intense tracer uptake, while all 15 neurinomas were negative (P<0.001 by Fisher's exact test). It may be concluded that scintigraphy with¹¹¹In-octreotide is a useful diagnostic procedure in neurofibromatosis, complementing standard neuroradiological imaging procedures.     

Comparison of Indium-111-labeled leukocyte scintigraphy and Technetium-99m joint scintigraphy in rheumatoid arthritis and osteoarthritis

This study was undertaken to evaluate the use of Indium-111-labeled leukocyte (111In-WBC) imaging compared with Technetium-99m pertechnetate (99mTcO4-) imaging in 19 patients with rheumatoid arthritis (RA) and 8 with osteoarthritis. Knee and wrist joints were evaluated for both radionuclides. The results indicated a good correlation of the clinical assessment of pain and swelling with joint uptake ratio (JUR) between 111In-WBC and 99mTcO4- in RA and osteoarthritis patients. We observed a discrepancy in both imagings in "burned out" cases. It was concluded that a JUR of 111In-WBC could distinguish active RA from inactive RA or osteoarthritis at a value of 1.15 and that the use of 111In-WBC was a more reliable procedure than 99mTcO4-.     

The value of octreotide scintigraphy in patients with lung cancer

We evaluated octreotide scintigraphy in 81 untreated patients who were suspected of having bronchial carcinoma. Octreotide scintigraphy visualized the primary tumour in all of 40 patients with non-smallcell lung carcinoma (non-SCLC), and all of 26 patients with SCLC. In the remaining patients, other bronchial disease and metastases from extrapulmonary carcinomas were also visualized. Mediastinal lymph node involvement and distant metastases were recognized in 5 of 15 and 1 of 7 patients with non-SCLC, respectively. In vitro, none of the non-SCLCs were shown to bear somatostatin receptors. We postulate that the visualization of non-SCLC during octreotide scintigraphy is caused by binding of labelled octreotide to activated leucocytes or to proliferating neuroendocrine cells around the tumours. In patients with SCLC, radiologically suspected lymph node involvement was visualized for 21 of 25 sites. Distant metastases, especially to the liver and abdomen, were missed for 14 of 20 sites, most probably because no laxatives were administered and single photon emission tomography of the abdomen was not performed. The failure to recognize liver metastases is most probably due to a comparable uptake of radioactivity by the surrounding normal liver tissue. In 15 of 26 patients, previously unrecognized tumour sites were suggested during octreotide scintigraphy, leading to a downstaging of 5 of 14 patients with limited disease. Unexpected cerebral metastases were suggested in five patients with either limited or extensive disease. In all four of these for whom follow-up was available, cerebral metastases became manifest 5–8 months after octreotide scintigraphy. We conclude (1) that octreotide scintigraphy is of no use to differentiate SCLC from other lung disease, and (2) that octreotide scintigraphy should be included in the staging procedure of SCLC because it may allow early detection of metastases, especially to the brain.     

The role of technetium-99m-labeled octreotide acetate scintigraphy in suspected breast cancer and correlates with expression of SSTR

PURPOSE: To evaluate the value of (99m)Tc-octreotide acetate (hereafter, (99m)Tc-octreotide) somatostatin receptor (SSTR) scintigraphy in the detection of primary breast cancer and to correlate with expression of SSTRs. MATERIALS AND METHODS: Fifty-four female and 1 male patients (range, 17-77 years; mean age, 48 years) with palpable breast lesion were included in this study. (99m)Tc-octreotide and (99m)Tc-MIBI scintigraphy were undertaken in all patients, and the region of interest was drawn around each lesion. Tumor uptake was measured and expressed as the ratio of tumor to normal tissue activity (T/NT). Final clinical diagnosis was confirmed by histopathological analysis. Expression of SSTR1-5 mRNA was measured with RT-PCR in 15 patients with malignant neoplasm, and protein level of SSTR-2 and SSTR-5 was measured using immunohistochemical staining in 15 patients with malignant neoplasm and 18 patients with benign lesion. RESULTS: Thirty-five patients were confirmed to have infiltrative ductal breast carcinoma, 1 patient with cellular cancer, 1 patient with adenocarcinoma and 18 patients had benign lesions. The sensitivity, specificity, positive predictive value and negative predictive value of (99m)Tc-octreotide in detection of primary lesion were 91.8%, 22.2%, 71.8% and 57.1%, respectively. No significant correlation was observed between T/NT of (99m)Tc-octreotide and (99m)Tc-MIBI. SSTR mRNA subtypes were variably expressed. SSTR3 was the most highly expressed, followed by SSTR1, SSTR2 and SSTR5; SSTR4 was the least expressed in the level of mRNA of SSTR. Significant correlation was shown between T/NT and the expression of SSTR2 mRNA (r=0.73, P<.01). CONCLUSION: (99m)Tc-octreotide acetate scintigraphy was sensitive for the detection of primary lesion of breast cancer; however, nonspecific breast tissue uptake hampered the specificity and clinical value in the detection of lymph node metastasis. Five subtypes of SSTR mRNA and protein SSTR2 and SSTR5 were expressed variably in breast cancer due to tumor heterogeneity. (99m)Tc-octreotide imaging may hold promise in the evaluation of the level of SSTR2 in vivo.     

The evolutional stage changes in sarcoidosis on gallium-67 scintigraphy

Gallium-67 scintigraphy has been proven as the imaging modality of choice in monitoring the presence of active disease in sarcoidosis. The purpose of this study is to analyze the patterns of evolutional stage changes of sarcoidosis while on steroid therapy by Ga-67 scintigraphy.Methods: Eighty-six consecutive patients with biopsy-proved sarcoidosis are evaluated by Ga-67 scintigraphy. Thirty-six of 86 patients have had a baseline and one to eight follow-up Ga-67 scintigraphs (total 136 studies). The initial follow-up scintigraphs are obtained on average about 4–12 months after the baseline study.Results: Seventeen of 36 patients (47.2%) are in stage IV at the time of the baseline study. Following their first course of corticosteroid therapy, 13 patients remained in the same stage and activity distribution pattern while 13 patients have shown reversion to other stages, eight patients showed complete remission while two patients became active from inactive stage.Conclusion: Evolutional stage changes are seen in 23 patients (63.9%), including eight patients (22.2%) who showed complete scintigraphic remission. The evolutionary stage changes remain quite variable and unpredictable. This, however, should not detract from the usefulness of Ga-67 scintigraphy in the diagnosis and prognostic evaluation of sarcoidosis, particularly when extrapulmonary involvement (Stage IV disease) is present.     

Subchondral pseudocysts in rheumatoid arthritis.

Subchondral cyst formation (geode) is a not uncommon manifestation of rheumatoid arthritis which may at times impede correct radiologic interpretation. Four patients with rheumatoid arthritis who demonstrated striking subarticular cystic erosive disease are described. These cases emphasize the nature and appearance of this interesting finding.     

Shoulder arthrography in rheumatoid arthritis.

Arthrograms of the shoulder were evaluated in 10 patients with rheumatoid arthritis. The arthrographic findings common to all joints consisted of nodular filling defects, irregular capsular attachments, bursal filling defects and visualized lymphatic drainage. Findings unique to the shoulder joint consisted of rotator cuff tear, frozen shoulder, and biceps sheath dilatation. Since the agents used to treat patients with rheumatoid arthritis have profound side effects, it is important to exclude an associated rotator cuff tear and/or confirm the presence of glenohumeral rheumatoid involvement.     

99m Tc-HMPAO labelled leukocyte scintigraphy in patients with rheumatoid arthritis: a comparison with disease activity.

The aim of this study was to test the applicability of 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) labelled leukocyte joint scintigraphy in the assessment of disease activity in 21 patients with rheumatoid arthritis, and to compare leukocyte scintigraphy with the Disease Activity Score (DAS), a validated activity index developed by the European League Against Rheumatism (EULAR). Twenty-one patients with rheumatoid arthritis were investigated by using 99mTc-HMPAO labelled leukocyte joint scintigraphy. The clinical and laboratory data were recorded, and the DAS was calculated and compared with the scintigraphic results in each case. A relatively high DAS score (4.71+/-1.07) was found in the majority of patients. The degree of accumulation of 99mTc-HMPAO leukocytes showed no correlation with a patient's age, gender, duration of disease, use of disease modifying anti-rheumatic drugs (DMARDs), visual analogue scale (VAS), Richie index, DAS, or any laboratory parameters. In contrast, a significant correlation was found between the global regional accumulation of the labelled leukocytes of the hands and feet, and the swollen-joint count. It is concluded that radiolabelled leukocyte scintigraphy could become one of the promising methods in the assessment of disease activity in patients with rheumatoid arthritis.     

Imaging of pulmonary disease in rheumatoid arthritis using J001X scintigraphy: Preliminary results

The purpose of this study was to determine the ability of technetium-99m J001X scintigraphy to image active pulmonary involvement in patients suffering from rheumatoid arthritis (RA). J001X is a fully characterized acylated poly(1,3)galactoside, isolated fromKlebsiella membranes, which is able to bind recruited macrophages after aerosol administration. J001X scintigraphy was compared with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs) and bronchoalveolar lavage (BAL) in 15 patients suffering from RA. Patients were considered to have pulmonary involvement when they had an interstitial syndrome on HRCT and a decrease of 20% in TCO/VE (transfer coefficient) on PFTs and/or an abnormal BAL (lymphocytosis higher than 20% and/or percentage of neutrophils higher than 10%). Pulmonary involvement was present in eight patients, and absent in seven. Of the eight patients with pulmonary involvement, all had abnormal BAL, two had an interstitial syndrome on HRCT, two had decreased TCO/VE and three had positive J001X scintigraphy. Of the seven patients without pulmonary involvement, six had normal BAL (not available in one), two had an interstitial syndrome on HRCT, one had decreased TCO/VE and two had positive J001X scintigraphy. According to our gold standard of pulmonary involvement, the sensitivity of J001X scintigraphy for the detection of pulmonary involvement in RA was 37.5%, the specificity was 71.4% and the positive predictive value was 60%. The ability of J001X scintigraphy to detect active pulmonary involvement during RA appears unclear in this study but it may detect processes unnoticed by the other modalities. These patients will be followed 12 and 24 months later and the changes in J001X scintigraphy, HRCT and PFTs will be compared to demonstrate whether J001X scintigraphy is able to assess an active process in the pulmonary involvement during RA and to specify its predictive value.     

The clinical role of nuclear medicine in rheumatoid arthritis patients. A comparison with other diagnostic imaging modalities.

In patients with rheumatoid arthritis (RA) synovitis activity is the dominant clinical variable that determines the therapeutic approach. At present, the amount of painful and swollen joints assessed by physical examination, is generally used to measure the degree of synovitis activity. A gold standard for the assessment of synovitis activity is not available. The availability of an objective and reproducible method to evaluate synovitis activity in RA would be of great value in patient management and in examination of therapeutic effects. An advantage of the use of radiopharmaceuticals in detection of arthritis activity, compared with other imaging techniques, is the possibility to depict all joints in a single image. Furthermore the technique may image joints which are difficult to assess clinically or radiographically and may also detect joint inflammation in an early phase. In this overview different scintigraphic techniques are compared with each other and with other diagnostic imaging modalities.     

The temporomandibular joint in rheumatoid arthritis

The temporomandibular joint (TMJ) was investigated clinically and by orthopantomography in 110 patients with rheumatoid arthritis (RA) and in 73 control subjects. Clinical symptoms in the TMJ were established in 34 per cent of the RA patients and in 18 per cent of the controls. Radiographic abnormalities were found in 60 per cent of the RA patients compared with 15 per cent in the controls. No single radiographic abnormality was characteristic of joint involvement by RA. The most common radiologic features in RA patients were changes in the morphology of the condylar head and articular eminentia, marginal irregularities, reduced mobility, and an anterior position of the condylar head. No abnormalities were encountered in the early stage of the disease, which at least in part could be attributed to the inherent limitations of orthopantomography. The incidence of joint lesions increased with duration of the RA.     

Visualizing inflammation activity in rheumatoid arthritis with Tc-99 m Anti-CD4-mAb fragment scintigraphy

PurposeT-cell-located CD4 antigen represents one of the therapeutic targets in rheumatoid arthritis (RA). However, up to now there is no established imaging tool to visualize this target in vivo. The aim of our study was to assess the safety and tolerability of a technetium-99 m labelled murine anti-human CD4 IgG1-Fab fragment ([^99mTc]-anti-CD4-Fab, [^99mTc]-EP1645) in patients with active synovitis due to RA, and to evaluate its potential as a marker of disease activity.MethodsIn the present phase I proof of principle study five patients with RA were examined. Planar scans of the whole body, hands, and feet were taken 30 min up to 24 h after application of 550 ± 150 MBq [^99mTc]-anti-CD4-Fab, followed by visual analyses, comparison with clinical data in 68 joints per patient and semiquantitative analysis of hand and wrist joints.ResultsNeither infusion related adverse events nor adverse events during follow up were observed. No increase in human anti-murine antibody titres was seen. All patients had positive scans in almost 70% of clinically affected joints. Positive scans were also found in 8% of joints without evidence of swelling or tenderness.ConclusionScintigraphy with [^99mTc]-anti-CD4-Fab is a promising technique for evaluation of inflammatory activity in patients with RA, pre-therapeutical evaluation of CD4 status and therapy control. Tracer uptake in clinically inconspicuous joints strongly indicates diagnostic potential of [^99mTc]-anti-CD4-Fab. Whether this technique is eligible as a prognostic factor in RA needs to be analysed in further studies as well as the pathophysiological background of clinically affected joints lacking tracer uptake.     

(99m)Tc-dextran scintigraphy to detect disease activity in patients with rheumatoid arthritis

AIM: To test the applicability of Tc-dextran joint scintigraphy in the assessment of disease activity in patients with rheumatoid arthritis (RA), and to compare it with the clinical disease activity scores and laboratory parameters. METHODS: Twenty-seven patients with RA were investigated using Tc-dextran joint scintigraphy. The images were evaluated semi-quantitatively and the regional uptakes of the radiopharmaceutical were calculated for the knee, wrist and ankle joints. The clinical and laboratory parameters were collected and fully analysed. An articular Ritchie index (a tender joint score), the number of swollen joints (Sw), the number of tender joints, the morning stiffness (h), the total Ritchie articular index (R), the visual analogue scale (VAS) and the Disease Activity Score (DAS) were determined for all patients. RESULTS: Compared with controls, patients with RA had significantly higher regional Tc-dextran uptake in the knee, wrist and ankle joints (P=0.001). The regional Tc-dextran uptake showed no correlation with the patient's age, gender, duration of disease, number of swollen joints (Sw), number of tender joints, morning stiffness (h), VAS, total Ritchie articular index and DAS, or any laboratory parameters. There was a significant correlation between the regional Tc-dextran uptake for individual joints and the articular Ritchie index of the right and left wrist (r=0.42, P=0.03; r=0.45, P=0.02), right and left knee (r=0.66, P<0.0001; r=0.80, P<0.0001) and right and left ankle (r=0.47, P=0.014; r=0.76, P<0.0001), respectively. CONCLUSIONS: This study demonstrates that Tc-dextran scintigraphy is a sensitive method to detect active joint inflammation and could be useful in the management of patients with RA.     

Bone and gallium scintigraphy in a patient with bone sarcoidosis

Periosteal reaction in bone lesions in patients with sarcoidosis is rare. We report a case with this type of bone sarcoidosis in whom bone and gallium scintigraphy were useful in detecting the lesions and making the diagnosis.     

The interphalangeal joint of the great toe in rheumatoid arthritis.

The radiographic abnormalities of the interphalangeal joint of the great toe in 50 patients with rheumatoid arthritis were compared with those in 14 patients with psoriatic arthritis. Alterations were seen in 50% of the rheumatoid joints. Characteristic superficial erosions along the medial aspect of the proximal and distal phalanges, with little change in the joint space, differed from more widespread and extensive destruction of this joint in psoriasis. In addition, periosteal proliferation, bony ankylosis and tuft resorption, frequently noted in psoriatic arthritis, were unusual in rheumatoid disease. An anatomic investigation of the interphalangeal joint of the great toe explains the sites of marginal erosions in rheumatoid arthritis. Although selective involvement of this articulation occurs in psoriatic arthritis and Reiter's syndrome, it is the radiographic pattern of articular abnormality which allows their differentiation from rheumatoid arthritis.     

Antefemoral dissecting cysts in rheumatoid arthritis.

Five cases of an antefemoral synovial cyst in rheumatoid arthritis were confirmed by arthrography. Communicating with the suprapatellar bursa, these rarely observed cysts may be considered an anterior analogy to dissecting Baker cysts.