Macrophage targeting with technetium-99m labelled J001 acylated poly-galactoside for scintigraphy of inflammation: Optimization and assessment of imaging specificity in experimental arthritis

J001, an acylated poly-(1,3)-galactoside purified from the membrane ofKlebsiella pneumoniae, associates selectively with macrophages via the binding to CD11b and CD14 molecules. Inflammatory foci known to recruit macrophages could thus be imaged with technetium-99m labelled J001. This study aims to define the optimal scintigraphic protocol for^99mTc-J001 imaging and to evaluate the specificity of J001 scans. A dose range study was conducted in rabbits with immunological arthritis using six different specific activities ranging from 370 to 11840 MBq·mg^–1 while the intravenously injected activity was constant (37 MBq) Radiochemical purity for each preparation was documented together with the in vivo stability of the^99mTc-J001 complex using exclusion-diffusion radioHPLC of serum collected 1 h after radiopharmaceutical administration. Scintigraphic images were recorded at 2, 3 and 4 h and analysed using indexes calculated from regions of interest. Specificity of the macrophage imaging was assessed by comparison with scans obtained after administration of^99mTcO₄ ^– or^99mTc-albumin nanocolloids. A protocol of plasma transfusion was also used to inject^99mTc-J001 after complete removal of radioactive colloids likely to be generated during the labelling. For the higher specific activities (5920 and 11840 MBq·mg^–1), radiochemical purity degradation and in vitro^99mTc transchelation were noted. To prevent transchelation and^99mTc bond hydrolysis likely to impair imaging specificity, 1480 MBq·mg^–1 corresponding to 25 µg injected J001 was found to be the optimal usable specific activity. Results obtained with the various tracers support the hypothesis that macrophage targeting is the main factor involved in the J001 imaging of arthritis.     

Multimodality imaging of renal inflammatory lesions

Spectrum of acute renal infections includes acute pyelonephritis, renal and perirenal abscesses, pyonephrosis, emphysematous pyelonephritis and emphysematous cystitis. The chronic renal infections that we routinely encounter encompass chronic pyelonephritis, xanthogranulomatous pyelonephritis, and eosinophilic cystitis. Patients with diabetes, malignancy and leukaemia are frequently immunocompromised and more prone to fungal infections viz. angioinvasive aspergillus, candida and mucor. Tuberculosis and parasitic infestation of the kidney is common in tropical countries. Imaging is not routinely indicated in uncomplicated renal infections as clinical findings and laboratory data are generally sufficient for making a diagnosis. However, imaging plays a crucial role under specific situations like immunocompromised patients, treatment non-responders, equivocal clinical diagnosis, congenital anomaly evaluation, transplant imaging and for evaluating extent of disease. We aim to review in this article the varied imaging spectrum of renal inflammatory lesions.     

Scintigraphic detection of inflammatory heart disease

Inflammatory diseases of the heart encompass myocarditis, endocarditis and pericarditis. This paper discusses the diagnostic potential of scintigraphy in these entities. In myocarditis, indium-111 antimyosin Fab imaging can visualize active myocyte damage and thus contribute substantially to the diagnosis. Antimyosin uptake is also seen in a large subset of patients with dilated cardiomyopathy, indicating ongoing myocyte injury in these cases. In endocarditis, immunoscintigraphy using monoclonal technetium-99m-labelled antigranulocyte antibodies provides useful diagnostic information in patients with equivocal echocardiographic findings. Immunoscintigraphy seems to indicate the floridity of the inflammatory process in endocarditis and may be used to monitor antibiotic therapy. In pericarditis, the clinical value of scintigraphy has not been convincingly demonstrated. Correspondence to: A.J. Morguet     

Scintigraphic evaluation of traumatic splenic lesions in children

Ninety-eight children with recent blunt abdominal trauma which initially evoked clinical suspicion of splenic injury were examined with colloid scintigraphy of the spleen and the liver using multiple imaging views and with abdominal survey. Nineteen children were, in addition, examined with tomographic scintigraphy. The clinical findings and the course of the disorder were reanalyzed. Scintigraphy indicated splenic injury in 56 children and hepatic injury in another 5 children. The left lateral and the left oblique were the optimum imaging views for detecting splenic ruptures. Tomographic scintigraphy did not improve the diagnostic yield. Abdominal survey failed to indicate almost every second case of splenic rupture and provided no additional information of significance. The clinical review agreed with the scintigraphic diagnosis of splenic lesions but, in addition, it suggested possible splenic lesions in another 10 children with normal scintigraphy. This discrepancy cannot be explained as surgery was not employed; the occurrence of splenic lesions too small to become detectable at scintigraphy or to provoke clinically evident symptoms may be supposed.     

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.     

Scintigraphic imaging of a nuchal sentinel node

The cutaneous lymphatic drainage of the trunk is complex and its prediction is used to rely on the classic anatomic concepts of Sappey. Lymphoscintigraphy has shown significant discrepancy between the real sentinel nodal basins and the expected sites of drainage based solely on the old lymphatic anatomy. The author presents a case of upper back melanoma with unusual nuchal sentinel node demonstrated by technetium-99m filtered sulfur colloid scintigraphy.     

Scintigraphic imaging of an unusual liver displacement

The authors present a patient with a mass in the right lung due to a partial herniation of the liver.     

Radiological imaging of inflammatory lesions in the nasal cavity and paranasal sinuses

Paranasal sinus development and pneumatisation variants are described, and rhinosinusitis and different patterns of inflammatory sinonasal diseases are reviewed. Other inflammatory sinonasal diseases, e.g., fungal sinusitis, mucocele, pyocele and sinonasal manifestations in systemic diseases, are briefly described. Computed tomography (CT) is the primary modality in diagnosing and mapping suspected inflammatory sinonasal disease. Magnetic resonance (MR) imaging is complementary to CT if fungal sinusitis, pyocele or malignancy are suspected.     

Immunoscintigraphic imaging of inflammatory lesions: preliminary findings and future possibilities

Mixed leukocytes separated in vivo from patients' blood and labeled with lipophilic chelates of 111In and 99mTc are now used clinically for imaging inflammatory foci in many medical centers worldwide. Recent immunological advances have prompted investigations about using radiolabeled antibodies potentially specific for human neutrophils, labeling of these blood cells in vivo, and imaging inflammatory processes in patients. Early results are encouraging, allowing abscesses to be imaged with high specificity and presenting only minimal (10% to 20%) adverse immunogenic responses. However, problems remain, including low immunospecificity and lengthy procedures for radiolabeling of antibodies. These areas are currently subjects to further research that in time will contribute to make this modality convenient, simple, and efficacious.     

Scintigraphic imaging of the heart in dogs damaged by irradiation

The paper verified literature data assuming that the heart damage caused by irradiation of thorax may be scintigraphically detected by means of 99mTc-pyrophosphate. Three dogs underwent a single irradiation of thorax with a gamma cobalt source by the Dose 40 Gy. The myocardium scan was performed 24 hours, 20 days, 50 days, 80 days and 93 days after the irradiation. The scintigraphic examination proved to be negative at all the intervals observed. A comparison of the scan with morphological findings and with radioactivity of tissue samples after the dogs were sacrificed 93 days after the irradiation proved that the negativity of the pyrophosphate scintigraphy was caused by a minimum damage of the myocardium and not by an inability of 99mTc-pyrophosphate to be incorporated into radiation lesions. The data in literature on myocardium damage by irradiation appear to be considerably exaggerated.     

Scintigraphic imaging of P-glycoprotein expression with a radiolabelled antibody

Purpose P-glycoprotein (P-gp) is a membrane efflux pump protein that is involved in multidrug resistance (MDR). Tumour cells with high P-gp expression show poor response to cancer treatment with several chemotherapeutics. In vivo targeting and visualisation of P-gp expression would allow MDR to be evaluated non-invasively prior to treatment. The aim of this study was to investigate the feasibility of visualising P-gp expression in tumours using a monoclonal anti-P-gp antibody, 15D3.Methods Nude BALB/c mice with subcutaneously growing human uterine sarcoma cell tumours with either high (MES-SA/D×5 1977) or low (MES-SA 1976) P-gp expression were used. When tumours were 0.2–0.4 g, mice received ¹³¹I-15D3 or ¹¹¹In-DTPA-15D3 monoclonal anti-P-gp antibody intravenously. Images were acquired up to 3 days p.i. and radioactivity concentration in various tissues was determined after euthanisation of the animals.Results The images demonstrated that radioactivity accumulated to a higher concentration in high P-gp expressing tumours than in the low P-gp expressing MES-SA 1976 tumour. Furthermore, visualisation of the P-gp expressing tumours was superior with ¹¹¹In-DTPA-15D3 than with ¹³¹I-15D3. After injection of ¹¹¹In-DTPA-15D3, the high P-gp expressing MES-SA/D×5 1977 tumours were clearly visualised at 3 days p.i. The biodistribution data indicated that radioactivity concentration in the high P-gp expressing tumours was higher than in the tumours with low P-gp expression (20.78±1.42 %ID/g for MES-SA/Dx5 1977 tumours and 8.39±3.78 %ID/g for MES-SA 1976 tumours for ¹¹¹In-DTPA-15D3).Conclusion The ¹¹¹In-labelled monoclonal anti-P-gp antibody clearly visualised P-gp expression in a human uterine sarcoma tumour in nude mice.     

Scintigraphic imaging of bacterial and fungal infection in granulocytopenic rats.

Scintigraphic imaging in granulocytopenic patients can be very useful to detect and localize infections, which often do not show localizing signs and symptoms. We studied the potential of 99mTc-labeled polyethylene glycol (PEG)-coated liposomes and 99mTc-labeled IgG to image bacterial and fungal infection in a granulocytopenic rat model. 67Ga-citrate was used as a reference agent. METHODS: 99mTc-PEG-liposomes, 99mTc-hydrazinonicotinate (HYNIC)-IgG or 67Ga-citrate was administered to granulocytopenic rats with a Staphylococcus aureus abscess or with unilateral invasive pulmonary aspergillosis. Imaging and biodistribution studies were performed. RESULTS: All agents visualized the S. aureus infection from 1 h after injection onward. However, only with 99mTc-PEG-liposomes and with 99mTc-HYNIC-IgG did activity in the infectious foci increase with time up to 24 h. 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG showed significantly higher accumulation in the infectious focus compared with 67Ga-citrate (1.33+/-0.31 and 1.40+/-0.16 percentage injected dose per gram [%ID/g], respectively, versus 0.31+/-0.04 %ID/g 24 h after injection; P<0.05). At 24 h after injection, abscess-to-muscle ratios were highest for 99mTc-liposomes (72.1+/-19.1), followed by 99mTc-HYNIC-IgG (18.3+/-3.3) and 67Ga-citrate (4.4+/-0.7). In pulmonary aspergillosis, both 99mTc-PEG-liposomes and 99mTC-HYNIC-IgG showed significantly higher uptake in the infected lung than did 67Ga-citrate (3.6+/-0.4 and 8.3+/-0.8 %ID/g, respectively, versus 1.3 %ID/g at 24 h after injection; P<0.05). CONCLUSION: 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG performed better than did 67Ga-citrate in the localization of peripheral bacterial infection and fungal infection in the lung in granulocytopenic rats. The high focal uptake and high target-to-nontarget ratios of 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG indicate that both radiopharmaceuticals may become valuable agents to image infection in granulocytopenic patients.     

双时相18F-FDG PET在肿瘤良恶性鉴别诊断中的应用

18F-FDG PET已较广泛地用于对恶性肿瘤的诊断和临床分期.常规显像一般用单次显像所测SUV(标准化摄取值)来鉴别良恶性病变,但两者SUV之间有一定交叉,存在一定局限性.而依据不同类型细胞18F-FDG摄取速率不同的机制,进行双时相18F-FDG PET(早期显像加延迟显像),简单而实用,具有较高的灵敏度、特异性和准确性.     

Evaluation of Tc-99m(V) DMSA for imaging inflammatory lesions: An experimental study

The present study evaluated^99mTc(V) DMSA as an agent for the visualization of inflammatory lesions in comparison to^99mTc(HI) DMSA and^99mTc-HIG. All three radiopharmaceuticals were prepared with commercial kits.^99mTc(V) DMSA was prepared at neutral pH by the addition of first bicarbonate and then pertechnetate to the kit contents. The labeling efficiency was 99% as determined by ITLC. Abscesses were induced by i.m. injection of 50 μl turpentine into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at 1,3,6 and 24 h later. Scintigrams were obtained with a gamma camera. The abscesses were better visualized on scintigrams with^99mTc(V) DMSA compared to^99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were removed, weighed and the radioactivity determined with a gamma counter. The abscess to other tissue ratios were higher with^99mTc(V) DMSA than the other radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 ± 3.20 (24 h), 4.19 ± 1.39 (6 h) and 5.98 ± 1.17 (24 h) and max. abscess/blood ratios were 6.22 ± 1.41, 4.09 ± 0.84 and 0.914 ± 0.351 all at 24 h for^99mTc(V) DMSA,^99mTc(III) DMSA and^99mTc-HIG, respectively. Experimental arthritis was produced in 6 New Zealand white rabbits by intra-articular injection of ovalbumin. Four days later 37 MBq of^99mTc(V) DMSA and^99mTc-HIG were each i.v. administered to 3 rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic joints. ROFs over arthritic joints were compared to contralateral normal joints (A/C). The max. A/C ratios were 2.10 ± 0.31 (3 h) and 2.92 ± 0.99 (24 h) for^99mTc(V) DMSA and^99mTc-HIG, respectively. Our results indicated the feasibility of imaging inflammatory lesions with^99mTc(V) DMSA.     

Scintigraphic imaging of experimental colitis with technetium-99m-infliximab in the rat

The radiolabeled monoclonal antibody (99m)Tc-infliximab was assessed as an inflammation imaging agent in a rat colitis model in comparison with (99m)Tc-tin colloid-labeled-leucocytes. (99m)Tc-infliximab and (99m)Tc-tin fluoride colloid-labeled-leucocytes were administered to (n>3) rats previously exposed to 2,4,6-trinitrobenzenesulfonic acid by rectal instillation. Whole body scintigraphic images were acquired and physiological organ assays were performed to obtain quantitative data. Histological examination of colon samples was performed to assess the site and severity of the colitis. In the inflamed colon, (99m)Tc-infliximab resulted in inflamed target (T) to control (C) colon tracer uptake ratios of 2.7 +/- 1.0 (n=5) and 2.6 +/- 0.3 (n=5) at 1 and 4 h post tracer injection respectively. (99m)Tc-leucocytes gave higher ratios of 19.5 +/- 9.9 (n=3) and 41.2 +/- 16.1 (n=5) respectively. (99m)Tc-leucocytes gave higher ratios of 19.5 +/- 9.9 and 41.2 +/- 16.1 at the corresponding time points. (99m)Tc-infliximab accumulated at sites of inflammation in this rat model but not due to a specific tumor necrosis factor-alpha binding mechanism. Although the tracer uptake was lower than radioactive leucocytes, this easily prepared (99m)Tc-monoclonal antibody may have some advantages in imaging inflammatory bowel disease in humans based on its biological activity.     

Scintigraphic techniques in primary hyperparathyroidism: from pre-operative localisation to intra-operative imaging

Introduction Primary hyperparathyroidism (PHPT) is an increasingly diagnosed disease worldwide. In most cases, PHPT is related to the presence of a solitary parathyroid adenoma (PA). Fifty percent or more of newly diagnosed PHPT patients are asymptomatic, and there is debate among endocrinologists and endocrine surgeons about whether or not such patients should be treated. Localization Usually, in a PHPT patient with a solitary PA that is well localised pre-operatively, a parathyroidectomy with limited or minimally invasive neck exploration is offered. The diffusion of minimally invasive neck exploration procedures is a consequence of the significant improvement in the accuracy of pre-operative imaging (mainly scintigraphic) techniques; these techniques have changed the surgical strategy to PHPT, from the wide traditional bilateral neck exploration to limited neck exploration. Review The present review considers developments during the past 10–15 years with regard to both the accuracy of pre-operative localising imaging techniques and intra-operative minimally invasive procedures in order to provide endocrinologists and endocrine surgeons with further information about the newly available diagnostic and therapeutic tools for use in PHPT patients with a solitary PA.