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Identification of an infected left ventricular assist device after cardiac transplant by indium-111 WBC scintigraphy.

PURPOSE: The purpose of this case report is to demonstrate the utility of multimodality imaging in the diagnosis of infection within a retained prosthetic device in the posttransplant setting. MATERIAL AND METHODS: Autologous leukocytes were labeled in vitro with indium-111 oxine and were reinjected. Whole-body and SPECT images were acquired at 24 hours and correlated with contemporary CT images. RESULTS: Through the use of combined indium-labeled WBC scintigraphy and CT we were able to identify infection within retained left ventricular assist device tubing status postcardiac transplantation in a patient with a diagnosis of fever of unknown origin. CONCLUSION: Localization of possible infectious etiologies within the transplant population is of utmost concern. Multimodality imaging, often utilizing scintigraphic techniques, is recommended.

Heart Ventricles↗

Trauma and inflammation modulate lymphocyte localization in vivo: quantitation of tissue entry and retention using indium-111-labeled lymphocytes.

OBJECTIVE: Determine the in vivo localization pattern of indium-111-labeled lymphocytes after a standardized extremity injury or standardized laparotomy and after sterile inflammation of the central nervous system. DESIGN: Prospective animal study with concurrent controls. SETTING: Animal research laboratory. SUBJECTS: Male Lewis rats weighing 150-175 g. INTERVENTIONS: Indium-111-labeled splenic lymphocytes were injected into animals after a standardized hind limb trauma or laparotomy and after induction of sterile central nervous system inflammation. MEASUREMENTS AND MAIN RESULTS: Lymphoid and non-lymphoid organs were removed at fixed intervals after lymphocyte injection and the proportion of injected lymphocytes/gram of tissue was determined using a quantitative radionuclide calculation. Results from treated animals were compared with results from untreated control animals. Muscle injury caused early localization of lymphocytes to injured hind limbs, liver, and spleen compared with controls, whereas laparotomy decreased lymphocyte localization in the thymus and colon. Encephalitis increased localization to the central nervous system with no effect on other tissues. CONCLUSIONS: These results identify a sensitive method to track in vivo leukocyte localization and specifically demonstrate that lymphocyte localization is altered in both traumatic and nontraumatic models of inflammation.

Animals↗

Benchmark test of neutron transport calculations: indium, nickel, gold, europium, and cobalt activation with and without energy moderated fission neutrons by iron simulating the Hiroshima atomic bomb casing.

A benchmark test of the Monte Carlo neutron and photon transport code system (MCNP) was performed using a bare- and energy-moderated 252Cf fission neutron source which was obtained by transmission through 10-cm-thick iron. An iron plate was used to simulate the effect of the Hiroshima atomic bomb casing. This test includes the activation of indium and nickel for fast neutrons and gold, europium, and cobalt for thermal and epithermal neutrons, which were inserted in the moderators. The latter two activations are also to validate 152Eu and 60Co activity data obtained from the atomic bomb-exposed specimens collected at Hiroshima and Nagasaki, Japan. The neutron moderators used were Lucite and Nylon 6 and the total thickness of each moderator was 60 cm or 65 cm. Measured activity data (reaction yield) of the neutron-irradiated detectors in these moderators decreased to about 1/1,000th or 1/10,000th, which corresponds to about 1,500 m ground distance from the hypocenter in Hiroshima. For all of the indium, nickel, and gold activity data, the measured and calculated values agreed within 25%, and the corresponding values for europium and cobalt were within 40%. From this study, the MCNP code was found to be accurate enough for the bare- and energy-moderated 252Cf neutron activation calculations of these elements using moderators containing hydrogen, carbon, nitrogen, and oxygen.

Cobalt↗

Comparison of indium-111 scintigraphy and colonoscopy with histologic study in children for evaluation of colonic chronic inflammatory bowel disease.

Indium-111 leukocyte scanning and colonoscopy were performed in 19 children and adolescents with chronic inflammatory bowel disease to study the correlation of evaluation between these two diagnostic modalities in comparison to histologic study for colonic disease. Seven patients had ulcerative colitis, 10 had Crohn's disease, and two patients had no specific diagnosis after evaluation. The sensitivity of indium-111 scan was 18%, specificity was 62.5%, and accuracy for diagnosing colonic disease was only 37%. In comparison, sensitivity and specificity for colonoscopy were 100 and 57%, respectively. Furthermore, accuracy with colonoscopy was 84%. Our data suggest that the usefulness of scans is limited to patients in whom standard diagnostic procedures are contraindicated. In addition, it is essential to confirm the visual diagnostic impression on colonoscopy with histologic study.

Adolescent↗

Renal scintigraphy and survival of indium-111-labelled platelets in patients with diabetic nephropathy.

Nine patients with overt diabetic nephropathy underwent renal scintigraphy and measurement of platelet survival time using indium-111-labelled platelets after treatment for six weeks with aspirin-dipyridamole (990 mg/225 mg/day) or placebo in a double-blind cross-over study. External scanning of the renal areas at 16 and 40 h post-injection showed no excess activity of indium-111 relative to background. Mean platelet survival was within the published normal range at 9.1 +/- 0.6 days and 7.6 +/- 1.4 days using linear and gamma function analyses respectively. Treatment with aspirin-dipyridamole was without effect. The results suggest that significant platelet deposition in renal blood vessels is not an important factor in the pathogenesis of diabetic nephropathy.

Aspirin↗

Indium-111 platelet kinetics in patients with diabetes mellitus.

We performed in vitro aggregation and indium-111 labeled platelet kinetic and biodistribution studies in seven patients with diabetes mellitus and in five control subjects. All subjects were male. All diabetic patients were poorly controlled at the time of study with blood glucose greater than 140 mg % and hemoglobin A1c greater than 10%. In vivo kinetic and biodistribution studies were performed following reinjection of autologous platelets labeled with indium-111 oxine in a dose of approximately 50 microCi (42-67 microCi). Images obtained at 4 and 24 h were computer-analyzed to determine splenic and hepatic uptake, and platelet survival times were calculated using four mathematical models. Unexpectedly, diabetic patients with fewer vascular complications tended to have shorter platelet survival times than patients with advanced vascular disease. However, no significant differences were observed between diabetic and control groups for any of the parameters of platelet function evaluated.

Blood Platelets↗

Indium-111 monoclonal anti-myosin antibody in assessing skeletal muscle damage in trauma.

Accurate assessment of the severity of soft tissue damage particularly skeletal muscle associated with fractures in trauma patients is important in determining the plan of management and prognosis. We used Indium-111 labelled anti-myosin to determine the extent of skeletal muscle injury in five patients involved in traumatic accidents. We found abnormal uptake in all 20 sites of muscle injury in four patients, 13 at the sites of fractures and seven away from fracture sites. There was good correlation between the degree of uptake and the extent of muscle injury. No uptake was seen in a case with no fracture and no muscle injury. At surgery this case proved to be haemarthrosis of the left knee. Indium-111 anti-myosin scanning is a potentially sensitive and useful technique in assessing extent of acute muscle injury in trauma patients.

Accidents↗

Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

PURPOSE: To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). METHODS: PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. RESULTS: Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. CONCLUSION: PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

Animals↗

Use of indium-111-labeled cells in measurement of cellular dynamics of experimental cardiac allograft rejection.

This study evaluates the kinetics and utility of infused indium-111-labeled cells in detecting rejection in ACI to Lewis rat heart allografts. Syngeneic leukocytes, lymph node lymphocytes, and platelets were isolated and labeled with indium-111 (111In) oxine, respectively, and were infused i.v. into Lewis rats carrying beating ACI or syngeneic hearts from post-transplant days 0 to 6. Recipients were imaged serially at 24 hr after infusion of labeled cells followed by excision of both native and transplanted hearts for direct isotope count. Labeled leukocytes accumulative progressively in the allograft with the scan becoming positive by post-transplant day 4. The ratio of allograft to native heart isotope counts rose from 1.25 on day 1 to 10.07 (P less than 0.0001) on day 7. The Lewis recipients infused with labeled lymphocytes showed a positive scan on days 6 and 7 whereas the allograft to native heart isotope count ratio rose from 0.97 on day 1 to 5.33 (P less than 0.001) on day 7. Recipients infused with 111In-labeled platelets showed a positive scan on days 5 to 7 and the allograft to native heart isotope count ratio rose sharply from 2.56 on day 4 to 16.98 (P less than 0.005) on day 7. Syngeneic heart grafts failed to demonstrate significant accumulation of any of the labeled cell population. These studies confirm the importance of nonlymphocytic cells in cellular rejection, evaluate the kinetics of graft invasion by the various cell types, and suggest that the techniques used afford a method for a safe and an early detection of allograft rejection.

Animals↗

Indium-111 labeled vitamin B12 imaging of a ciliary adenoma with concurrent grade 2 soft tissue sarcoma of the leg in a Labrador Retriever.

An 11-year-old, male castrated, Labrador Retriever was evaluated for the presence of rapidly growing concurrent leg and intraocular masses. Metastasis was noted in the chest at time of initial presentation. Indium-111 labeled vitamin B12 imaging was performed, and there was significant uptake by both primary tumors and the lung metastases. Enucleation and amputation were performed for palliative relief. The leg mass was a grade 2 soft tissue sarcoma and the ocular mass a ciliary adenoma. The dog remained symptom-free for approximately 10 weeks before developing signs of respiratory distress. He was euthanized 12 weeks after initial presentation, and there was diffuse infiltration of the lungs with metastatic sarcoma. Indium-111 labeled vitamin B12 imaging identified a ciliary adenoma in this case and may provide a useful differentiation technique for evaluation of intraocular and retrobulbar masses if it can be demonstrated that there is differential uptake between inflammatory or infectious conditions and neoplasia.

Adenoma↗

Tumour imaging of indium-111 oxine-labelled autologous lymphocytes as a staging method in Hodgkin's disease.

Following indium-111 oxine-labelled autologous lymphocyte infusion, 39 lymphocyte scintigraphies were performed in 35 patients with Hodgkin's disease (HD). Lymphocytes were obtained after leukapheresis and Lymphoprep gradient centrifugation and were further purified by an adherence step to eliminate monocytes. A median of 1.2 (0.2-3.7) X 10(9) cells were labelled with 6.7 (range 1.9-16.6) Mbq indium-111 oxine and reinfused to the patients. Gamma camera imaging was performed with a GE 400 AT. An accumulation of radioactivity was seen at 54 of 61 sites with enlarged lymph nodes. Increased radioactivity was also seen at 16 sites with no previous clinical evidence of tumour involvement. These data seem very promising and with further methodological improvement lymphoscintigraphy may prove to be an important complement in the staging procedure and follow-up of patients with HD.

Adolescent↗

Kinetics of indium-III labelled lymphocytes in normal subjects and patients with Hodgkin's disease.

The distribution in the body and the circulation in the blood of autologous lymphocytes labelled with indium-III were studied in two normal subjects and two patients with Hodgkin's disease. Four hours after injection radioactivity was identified in the spleen, liver, and bone marrow. Radioactivity, followed by imaging and whole body scanning, began to appear in the lymph nodes four to 18 hours after injection, and some, though not all, lymph node groups in the body could be readily visualised. There were no differences between the normal subjects and the patients with Hodgkin's disease. The pattern of clearance of radioactivity from the blood was consistent with a normal circulation between blood and lymphoid tissues of the labelled lymphocytes. Since indium-111 stays firmly attached to the cell, it seems an ideal label for studying lymphocyte kinetics, and the use of this technique may have further clinical application.

Hodgkin Disease↗

Diagnosis of deep vein thrombosis using autologous indium-III-labelled platelets.

Forty-eight patients who had undergone surgical reduction of a fractured neck of femur or in whom deep vein thrombosis was suspected clinically were studied by ascending phlebography and imaging after injection of autologous indium-111-labelled platelets to assess the accuracy and value of the radioisotopic technique in diagnosing deep vein thrombosis. Imaging was performed with a wide-field gammacamera linked with data display facilities. Phlebography showed thrombi in 26 out of 54 limbs examined and a thrombus in the inferior vena cava of one patient; imaging the labelled platelets showed the thrombi in 24 of the 26 limbs and the thrombus in the inferior vena cava. The accumulation of indium-111 at sites corresponding to those at which venous thrombi have been shown phlebographically indicates that this radioisotopic technique is a useful addition to methods already available for the detection of deep vein thrombosis.

Femoral Neck Fractures↗

Dynamic studies of lymphocytes labelled with indium-111 during and after treatment with monoclonal anti-idiotype antibody in advanced B cell lymphoma.

The migration pattern of lymphocytes labelled with indium-111 was followed in a patient with B cell non-Hodgkin's lymphoma treated with a murine monoclonal anti-idiotype antibody. During the early phase of continuous infusion of antibody rapid fluxes of labelled lymphocytes into and out of the blood were seen. Dynamic scanning showed immediate uptake in the lungs; thereafter activity decreased in the lungs and increased in the liver. Studies of labelled and unlabelled cells in the circulation showed that treatment resulted in the removal of lymphocytes from the blood which was repopulated from an extravascular compartment. Tumour cells were shown to be cleared from the blood by the reticuloendothelial system in the liver. Indium-111 should be used circumspectly because it may cause chromosomal damage in labelled cells, but it is clearly useful as a radiolabel for following the migration pathways of lymphocytes in vivo.

Aged↗

Evaluation of indium scintigraphy in patients with active inflammatory bowel disease.

Recent reports have indicated a possible role for 111Indium leucocyte scintigraphy in the management of patients with acute inflammatory bowel disease. Our experience with this technique in 15 patients (nine with ulcerative colitis, six with Crohn's disease) is described. Perfect agreement was not obtained between scintigraphic appearances and other conventional means in the assessment of extent of disease. Good correlation, however, was found between disease activity and recovery of labelled leucocytes in the faeces. While this latter finding could be used as an objective means of assessing response to therapy, it is concluded that conventional indium scintigraphy, using indium oxine-labelling of mixed leucocytes, is insufficiently reliable to replace usual methods for determining extent of disease in patients with inflammatory bowel disease.

Colitis, Ulcerative↗

Detection of left atrial thrombi in man using indium-111 labelled autologous platelets.

A scintigraphic technique using indium-111 labelled platelets to detect left atrial thrombi was used in 28 patients, 14 of whom had mitral valve disease and 14 combined valve disease. Imaging was performed in the anterior, right anterior oblique (45 degrees), and left lateral views on the day of injection and thereafter at one or two day intervals for a maximum of four days. When scintiphotos obtained in two or three views 72 or 96 hours after the platelet injection showed "hot spot areas" within the left atrial pool and indium-111 activity in these areas did not decrease with time they were interpreted as positive for thrombi. Of 28 patients, seven had positive platelet images by this criterion; of these, three underwent surgery and were found to have left atrial thrombi. One patient died, and a thrombus was found at necropsy. The remaining 21 patients had normal scintiphotos; of these, seven had no thrombi at operation and one had false negative images. The diagnostic accuracy of platelet scintigraphy by this criterion of positivity in the 12 patients in whom surgical or postmortem confirmation of thrombi could be obtained was 92%. These results indicate that this technique is a promising method for detecting active left atrial thrombi.

Adult↗

Evaluation of catheter thrombogenicity in vivo with indium-labeled platelets.

Platelets labeled with a lipid-soluble indium-111 8-hydroxyquinoline (oxine) complex were evaluated as an agent to measure the rate and degree of in vivo platelet accumulation on catheters. Polyethylene catheters and Teflon-coated guidewires were inserted into the femoral arteries or veins of dogs that had been injected with indium-labeled platelets. The catheters were passed to either the abdominal aorta or inferior vena cava and left in situ for 30 minutes to three hours. Images were obtained every five minutes with a gamma camera. This labeling technique is reproducible, allows multiple testing with a single preparation, and is relatively noninvasive. The results are easily quantitated to allow testing of different materials and coatings.

Animals↗

Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice.

Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study of parasitic and allergic disease.

Animals↗