Contribution of contaminant indium-114m/indium-114 to indium-111 oxine blood dosimetry

Indium-114m and 114In appear as contaminants in commercial preparations of [111In]oxine at a level of about 0.05% at time of calibration (TOC). The contribution of these contaminants to the radiation absorbed dose from [111In]oxine leukocyte, platelet, and erythrocyte imaging procedures has been evaluated. When the absorbed dose from these contaminants is expressed as a percent of the 111In dose to the same organ from a given procedure, the contaminants contribute an additional 0.16 to 12% of the 111In dose, and in one case, that of the spleen from [111In]oxine labeled erythrocytes, they contribute an additional 33%. Commercial samples of aqueous-based [111In]oxine contain levels of 114mIn/114In sufficient to result in a mild to moderate increase in the absorbed radiation dose to the patient. Strict quality control procedures must be maintained by suppliers to prevent higher contamination levels. It is advisable to avoid using 111In products of this nature later than about 3 days after the time of calibration.     

Comparison of leukocytes labeled with indium-111-2-mercaptopyridine-N-oxide and indium-111 oxine for abscess detection

Indium-111 leukocyte scanning has evolved into a practical and highly accurate method for the identification of infectious and inflammatory processes. The most commonly used agent for labeling leukocytes has been [111In]oxine. We have investigated a newer agent, 2-mercaptopyridine-N-oxide (Merc) at our institution which unlike oxine, allows us to label leukocytes in plasma, using a simple kit procedure. Of the 92 consecutive patients referred for detection or localization of an infectious process, autologous leukocytes of 55 patients were labeled with [111In]Merc, while those of the remaining 37 patients were labeled with [111In]oxine. The sensitivities for Merc and oxine procedures were 87% and 92%, respectively, while the respective specificities were 100% and 92%. We conclude that the [111In]Merc-labeled leukocytes are equally effective as [111In]oxine-labeled leukocytes in detecting infectious processes. The use of [111In]Merc is advantageous over [111In]oxine for white blood cell labeling because of its easier preparation.     

Neutrophil labeling with indium-111: tropolone vs. oxine

This study was undertaken to compare tropolone with oxine (8-hydroxy-quinoline) for labeling human neutrophils with In-111. Exposure of neutrophils to tropolone at concentrations required for efficient labeling resulted in a marked impairment of chemotaxis. In contrast, no impairment of neutrophil chemotaxis was observed using In-111 oxine. Labeling efficiencies obtained with In-111 tropolone under optimal conditions were consistently less than those obtained with In-111 oxine. We evaluated cells labeled by the two methods using chemotaxis radioassay to assess the chemotatic potential of labeled cells. The results led to the conclusion that the oxine technique is preferable to tropolone for labeling human neutrophils with In-111.     

Cell labelling and cell damage with indium-111 acetylacetone-an alternative to indium 111 oxine

The labelling of HeLa S3 cells with 111In acetylacetone (111In-acac) was studied together with cell damage, measured by the reduction in colony-forming ability of labelled cells. Using 2 X 10(5) cells/ml in Hepes saline buffer at pH 7.6 incubated with 7.4-185 kBq (0.2-5.0 microCi)/ml 111In-acac, containing 0.19% acetylacetone for 15 minutes at room temperature, 60-80% 111In was bound to the cells. The cell binding was linear with activity and resulted in an exponential reduction in colony forming ability and a D0 of 26 kBq (0.7 microCi)/2 X 10(5) cells. Radiation was shown to be the major cause of cell damage. It is concluded that 111In-acac is preferable to 111In oxine because it is soluble in physiological buffers, which eliminates the use of ethanol; it is quick and easy to prepare; and compared with previous results using HeLa S3 cells labelled with 111In oxine, 111In-acac gives much more reproducible results and is no more toxic. Clinically 111In-acac was shown to give similar results to 111In oxine.     

Nonvisualization of the liver by indium-111 oxine labeled leukocytes in alcoholic liver disease

The liver was not visualized by In-111 WBC scan in a patient with alcoholic liver disease. The liver was visualized on repeat scan when liver function had improved.     

Comparison of oxine and tropolone methods for labeling human platelets with indium-111

The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with 111In-oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In-oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly.     

Evaluation of the utility of indium-111 oxine platelet imaging in renal transplant patients on cyclosporine

Twenty five In-111 oxine platelet imaging procedures were performed in 21 renal transplant patients to assess the value of this study for diagnosis of renal transplant rejection in recipients receiving cyclosporine (CYS) for immunosuppression. Fourteen biopsies were performed, and an extensive, in-depth review of the clinical progress of each patient was obtained. There was no ideal "gold standard" to which our imaging results could be compared, but we used a combination of biopsy findings, clinical impressions, and changes in renal function after pulsing with steroids and/or decreasing CYS dosage as the basis for our diagnoses. We were unable to distinguish between renal rejection and CYS toxicity using platelet imaging. The sensitivity of the platelet procedure for diagnosing rejection or CYS toxicity was 100%. The specificity for rejection or CYS toxicity was only 76.5%. In view of the inability of this test to distinguish between rejection and CYS toxicity, its rather low specificity, and its relatively high cost, it is not a particularly helpful study for the diagnosis of renal transplant rejection in patients on CYS.     

The use of indium-111 oxine platelet scintigraphy and survival studies in pediatric patients with thrombocytopenia

We have utilized 111In-labeled heterologous platelets to investigate the mechanism of thrombocytopenia in ten children. From the scintigraphic findings, platelet survival times, and clinical information, thrombocytopenia was ascribed to decreased production or to increased destruction. Two patients were found to have bone marrow production defects. Two patients with hemangiomas were studied. In one, the hemangioma was shown not to be the cause of thrombocytopenia. In the second, the hemangioma was proven the source of platelet destruction, but was much more extensive than clinically evident. In both, surgical manipulation of the hemangioma was avoided. Six additional patients had thrombocytopenia due to accelerated destruction. In four, the spleen was shown responsible. In two, however, the spleen was shown not to be responsible for the low platelet counts, and splenectomy was avoided. Thus, 111In-platelet scintigraphy and survival studies are valuable in the classification and management of childhood thrombocytopenia. We believe that this study should be performed, when possible, in any child with thrombocytopenia where the mechanism is unclear or the therapeutic intervention involves splenectomy or resection of a hemangioma.     

Visualization of right atrial thrombus associated with constrictive pericarditis by indium-111 oxine platelet imaging

A right atrial thrombus is not often seen and only a few reports of visualization have been described. We report a 44-yr-old man who had a large atrial thrombus associated with constrictive pericarditis. Two-dimensional echocardiography and computed tomography showed a large right atrial mass. Indium-111 oxine platelet deposition was demonstrated on the surface of thrombus by platelet imaging. Platelet imaging was useful for differential diagnosis from cardiac tumor, and as an indication for surgical treatment, since right atrial thrombus may have a high risk of pulmonary embolism or severe right heart failure.     

Clinical comparison of indium-111 acetylacetone and indium-111 tropolone granulocytes

This clinical study compares the efficacy of two 111In white blood cells preparations. Seventy-six patients were imaged after an injection of granulocytes (GRAN) isolated on a Ficoll-Hypaque gradient and labeled with [111In]acetylacetone (ACAC) in saline; 105 patients were imaged after an injection of GRAN isolated on a metrizamide-plasma gradient and labeled with [111In]tropolone (TROP) in plasma. Early (2-4 hr), intermediate (4-6 hr), and delayed (24 hr) images were obtained. The specificity was quite high (94-100%) in both preparations and no statistical differences could be found. The sensitivity for ACAC-GRAN for the early, intermediate, and delayed images were 39%, 63%, and 64%, respectively; for TROP-GRAN it was 80%, 89%, and 92%, respectively. In all cases the TROP-GRAN images were significantly more sensitive than the ACAC-GRAN images obtained at the same time after injection (p less than 0.001 for early and delayed images, 0.01 less than p less than 0.025 for intermediate images). For ACAC-GRAN the intermediate and delayed images were significantly more sensitive than the early images, while no significant difference could be found for TROP-GRAN. In a blinded experiment, the ability of TROP-GRAN to demonstrate a lesion was compared to that of ACAC-GRAN. TROP-GRAN demonstrated the lesions better than ACAC-GRAN, both in the early and late images (p less than 0.001). TROP-GRAN visualization scores at 4-6 hr equaled those obtained 24 hr after injection. In conclusion, GRAN separated and labeled in plasma with TROP are superior to those separated and labeled in saline with ACAC in three ways: higher visualization scores, earlier visualization of the lesion, and greater sensitivity.     

Comparison of indium-111 oxinate labelled autologous granulocytes with indium-111 oxinate and indium-111 chloride as abscess scanning agents

Bacterial abscesses were evoked in goats. Imaging of these abscesses was obtained by means of labelling autologous granulocytes with ¹¹¹In oxinate, reinjection of the cells into the animal, and scintigraphy by gamma camera one day later. Comparable imaging results, however, were obtained after intravenous injection of ¹¹¹In oxinate or of ¹¹¹In chloride.The gamma camera images were supported by tissue distribution studies. In the case of administration of ¹¹¹In oxinate to the goats, the radioactivity accumulated in the cell fraction of the blood to a significant extent. This did not occur in the case of plain ¹¹¹In chloride. It remained unexplained why such different accumulation in cells did not result in differences in the scintigraphic studies.Blood clearance studies supplied conclusive evidence that the granulocytes stayed in the circulation for several days following labelling with ¹¹¹In oxinate and reinjection of the cells into the animals.     

Comparison of indium-111 nonspecific polyclonal IgG with indium-111-leukocytes in a canine osteomyelitis model

Osteomyelitis was surgically produced in the proximal tibia of ten dogs. A sham operation was performed on the other tibia. Early (3 hr) and late (20 hr) imaging was performed 1, 4, 7, 10, and 13 wk later, while the osteomyelitis progressed from acute to chronic. Indium-111-IgG had a significantly greater accumulation at the osteomyelitis site than 111In-leukocytes, both during early (p = 0.001) and late (p = 0.03) imaging, and at each of the weeks studied (p less than 0.001). During early imaging, both agents gave equivalent lesion to background ratios. On the late images, the 111In-leukocytes gave significantly higher lesion-to-background ratios than 111In-IgG (p less than 0.001) and higher ratios than they did during the early images (p less than 0.001). Both agents had greater accumulation in acute osteomyelitis than in chronic osteomyelitis (p less than 0.02). Osteomyelitis in the surgical site can be distinguished from the uptake in the sham surgery site using 111In-leukocytes, but not when using 111In-IgG.     

Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells

Purpose Cell-based therapy by transplantation of progenitor cells has emerged as a promising development for organ repair, but non-invasive imaging approaches are required to monitor the fate of transplanted cells. Radioactive labelling with ¹¹¹In-oxine has been used in preclinical trials. This study aimed to validate ¹¹¹In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells. Methods Murine haematopoietic progenitor cells (10⁶, FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose) ¹¹¹In-oxine and compared with unlabelled controls. Cellular retention of ¹¹¹In, viability and proliferation were determined up to 48 h after labelling. Labelled cells were injected into the cavity of the left or right cardiac ventricle in mice. Scintigraphic images were acquired 24 h later. Organ samples were harvested to determine the tissue-specific activity. Results Labelling efficiency was 75 ± 14%. Cellular retention of incorporated ¹¹¹In after 48 h was 18 ± 4%. Percentage viability after 48 h was 90 ± 1% (control), 58 ± 7% (low dose) and 48 ± 8% (high dose) (p<0.0001). Numbers of viable cells after 48 h (normalised to 0 h) were 249 ± 51% (control), 42 ± 8% (low dose) and 32 ± 5% (high dose) (p<0.0001). Cells accumulated in the spleen (86.6 ± 27.0% ID/g), bone marrow (59.1 ± 16.1% ID/g) and liver (30.3 ± 9.5% ID/g) after left ventricular injection, whereas most of the cells were detected in the lungs (42.4 ± 21.8% ID/g) after right ventricular injection. Conclusion Radiolabelling of haematopoietic progenitor cells with ¹¹¹In-oxine is feasible, with high labelling efficiency but restricted stability. The integrity of labelled cells is significantly affected, with substantially reduced viability and proliferation and limited migration after systemic transfusion.