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Item does not contain fulltext Radiolabeled autologous leukocytes are the gold standard for imaging infectious foci in patients. Good results have also been reported for radiolabeled heterologous leukocytes from noninfected donors. Until now, the 2 methods have not been directly compared. In this study, we compared the infection-imaging potential of 99mTc-hexamethylpropyleneamine oxime (HMPAO)-labeled autologous granulocytes with that of 99mTc-HMPAO-labeled granulocytes from either infected or noninfected donors in rabbits with Escherichia coli infection. METHODS: The radiolabeled granulocyte preparations were studied in rabbits with an E. coli infection in the left calf muscle. The soft-tissue infections were scintigraphically visualized after injection of 18 MBq of either 99mTc-HMPAO purified autologous granulocytes or radiolabeled purified heterologous granulocytes from infected or noninfected donor rabbits. Gamma camera images were acquired at 2 min and at 1, 2, and 4 h after injection. After the last image, the rabbits were killed and uptake of the radiolabel in the dissected tissues was determined. RESULTS: The 99mTc-HMPAO autologous granulocytes and heterologous granulocytes from infected donors accurately revealed the infectious focus in the calf muscle at 2 h after injection. At 4 h after injection, a significantly better (P < 0.05) delineation of the infection was established with the 99mTc-HMPAO autologous granulocytes and 99mTc-HMPAO heterologous granulocytes from the infected rabbits than with the heterologous granulocytes from noninfected donors. With both cell preparations, the intensity of uptake in the infected calf muscle continuously increased until 4 h after injection. The 99mTc-HMPAO heterologous granulocytes from noninfected donors showed no significant increase in contrast after 2 h after injection. Absolute uptake in the infected calf muscle was much higher for 99mTc-HMPAO autologous granulocytes (7.81 +/- 1.21 percentage injected dose [%ID]) and 99mTc-HMPAO heterologous infected granulocytes (8.91 +/- 1.92 %ID) than for the radiolabeled heterologous noninfected granulocytes (2.32 +/- 0.75 %ID) (P < 0.04) at 4 h after injection. The ratio of infected muscle to noninfected contralateral muscle was significantly higher for 99mTc-HMPAO autologous granulocytes and 99mTc-HMPAO heterologous granulocytes from infected donors than for 99mTc-HMPAO heterologous granulocytes from noninfected donors (5.53 +/- 1.09, 3.86 +/- 0.75, and 1.86 +/- 0.31, respectively; P < 0.05). CONCLUSION: For nuclear medicine imaging of infection, purified granulocytes derived from infected rabbits are superior to purified granulocytes derived from noninfected donor rabbits. In addition, autologous granulocytes gave similar results to heterologous granulocytes from infected donor rabbits, suggesting the need for intrinsic cell activation for specific granulocyte migration.

Item does not contain fulltext Early and accurate diagnosis of osteomyelitis remains a clinical problem. Acute osteomyelitis often occurs in infants and most often is located in the long bones. Radiologic images show changes only in advanced stages of disease. Scintigraphic imaging with (99m)Tc-methylene diphosphonate (MDP), or bone scanning, is much more sensitive in detecting acute osteomyelitis but lacks specificity. We evaluated the performance of (99m)Tc-interleukin-8 (IL-8) in an experimental model of acute osteomyelitis. METHODS: Acute pyogenic osteomyelitis was induced in 10 rabbits by inserting sodium morrhuate and Staphylococcus aureus into the medullary cavity of the right femur. The cavity was closed with liquid cement. A sham operation was performed on the left femur. Routine radiographs were obtained just before scintigraphy. Ten days after surgery, the rabbits were divided into 2 groups of 5 animals, received an injection of either 18.5 MBq (111)In-granulocytes or 18.5 MBq (67)Ga-citrate, and were imaged both 24 h after injection and 48 h after injection. On day 12, the rabbits received either 18.5 MBq (99m)Tc-MDP or 18.5 MBq (99m)Tc-IL-8, and serial images were acquired at 0, 1, 2, 4, 8, 12, and 24 h after injection. Uptake in the infected femur was determined by drawing regions of interest. Ratios of infected femur (target) to sham-operated femur (background) (T/Bs) were calculated. After the final images were obtained, the rabbits were killed and the right femur was dissected and analyzed for microbiologic and histopathologic evidence of osteomyelitis. RESULTS: Acute osteomyelitis developed in 8 of 10 rabbits. All imaging agents correctly detected the acute osteomyelitis in these animals. The extent of infection was optimally visualized with (67)Ga-citrate and delayed bone scanning, whereas diaphyseal photopenia was noted with both (99m)Tc-IL-8 and (111)In-granulocytes. In 1 rabbit with osteomyelitis, imaging results were falsely negative with (111)In-granulocytes and falsely positive with (99m)Tc-MDP. Quantitative analysis of the images revealed that the uptake in the infected region was highest with (67)Ga-citrate (4.9 0.8 percentage injected dose [%ID]) and (99m)Tc-MDP (4.7 0.7 %ID), whereas the uptake in the infected area was significantly lower with (99m)Tc-IL-8 (2.2 0.2 %ID) and (111)In-granulocytes (0.8 0.2 %ID) (P < 0.0042). In contrast, the T/Bs were significantly higher for (99m)Tc-IL-8 (T/B, 6.2 0.3 at 4 h after injection) than for (67)Ga-citrate, (99m)Tc-MDP, and (111)In-granulocytes, which had ratios of 1.5 0.4, 1.9 0.2, and 1.4 0.1, respectively (P < 0.0001). Radiography correctly revealed acute osteomyelitis in only 2 of 8 rabbits. CONCLUSION: In this rabbit model of osteomyelitis, (99m)Tc-IL-8 clearly revealed the osteomyelitic lesion. Although the absolute uptake in the osteomyelitic area was significantly lower than that obtained with (99m)Tc-MDP and (67)Ga-citrate, the T/Bs were significantly higher for (99m)Tc-IL-8 because of fast background clearance. The ease of preparation, good image quality, and lower radiation burden suggest that (99m)Tc-IL-8 may be a suitable imaging agent for the scintigraphic evaluation of acute osteomyelitis.

Item does not contain fulltext Radiolabeled autologous leukocytes (WBCs) are the gold standard for imaging inflammatory bowel disease (IBD). For the rapid and adequate management of patients with IBD, there is need for a new agent at least as good as radiolabeled WBCs, but easier to prepare and without its inherent risks. In this study, the potential of interleukin-8 (IL-8) labeled with (99m)Tc using hydrazinonicotinamide (HYNIC) to image IBD was investigated in a rabbit model of acute colitis and compared with that of (99m)Tc-HMPAO-labeled granulocytes. METHODS: In rabbits with chemically induced acute colitis, inflammatory lesions were scintigraphically visualized after injection of either IL-8 or purified granulocytes, both labeled with (99m)Tc. Gamma camera images were acquired at 2 min and at 1, 2, and 4 h after injection. Four hours after injection, the rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. The dissected colon was imaged and the inflammatory lesions were scored macroscopically. For each affected colon segment, the colitis index (affected colon-to-normal colon uptake ratio, CI) was calculated and correlated with the macroscopically scored severity of inflammation. RESULTS: Both agents visualized the colitis within 1 h after injection. (99m)Tc-HYNIC-IL-8 images of the colonic abnormalities were more accurate and the intensity of uptake in the affected colon continuously increased until 4 h after injection, whereas no further increase 1 h after injection was noticed scintigraphically for (99m)Tc-HMPAO-granulocytes. The absolute uptake in the affected colon was much higher for IL-8 than for the radiolabeled granulocytes with the percentage injected dose per gram (%ID/g) 0.41 0.04 %ID/g and 0.09 0.05 4 %ID/g h after injection, respectively. With increasing severity, the CI at 4 h after injection for (99m)Tc-HYNIC-IL-8 was 4.4 0.6, 13.5 0.5, and 25.8 1.0; for granulocytes, the CI at 4 h after injection was 1.5 0.1, 3.4 0.2, and 6.4 0.5, respectively. The CI correlated with the severity of the inflammation (r = 0.95, P < 0.0001 for IL-8; r = 0.95, P < 0.0001 for granulocytes). CONCLUSION: Within 1 h after injection, visualization of the extent of colonic inflammation in vivo was possible with (99m)Tc-HYNIC-IL-8 and (99m)Tc-HMPAO-granulocytes. Within 2 h after injection, (99m)Tc-IL-8 allowed a good evaluation, and within 4 h after injection, a meticulous evaluation of the severity of IBD. Although (99m)Tc-HMPAO-granulocytes were able to delineate the extent of IBD within 2 h after injection, an accurate estimation of severity of inflammation was not possible. (99m)Tc-HYNIC-IL-8 is an inflammation-imaging agent that showed promising results in this study. (99m)Tc-IL-8 can be prepared off-the-shelf and yields excellent imaging with high target-to-background ratios.