Technetium-99m-labeled white blood cells: a new method to define the local and systemic role of leukocytes in acute experimental pancreatitis.

OBJECTIVE: We developed a new method to quantitate leukocyte accumulation in tissues and used it to examine the time course and severity of acute experimental pancreatitis. BACKGROUND: Leukocyte activation and infiltration are believed to be critical steps in the progression from mild to severe pancreatitis and responsible for many of its systemic complications. METHODS: Pancreatitis of graded severity was induced in Sprague-Dawley rats with a combination of caerulein and controlled intraductal infusion. Technetium-99m (99mTc)-labeled leukocytes were quantified in pancreas, lung, liver, spleen, and kidney and compared with myeloperoxidase activity. The severity of pancreatitis was ascertained by wet/dry weight ratio, plasma amylase, and trypsinogen activation peptide in the pancreas. The time course of leukocyte accumulation was determined over 24 hours. RESULTS: Pancreatic leukocyte infiltration correlated well with tissue myeloperoxidase concentrations. In mild pancreatitis, leukocytes accumulated only in the pancreas. Moderate and severe pancreatitis were characterized by much greater leukocyte infiltration in the pancreas than in mild disease (p < 0.01), and increased 99mTc radioactivity was detectable in the lung as early as 3 hours. 99mTc radioactivity correlated directly with the three levels of pancreatitis. CONCLUSIONS: Mild pancreatitis is characterized by low-level leukocyte activation and accumulation in the pancreas without recruitment of other organs; marked leukocyte accumulation was found in the pancreas and in the lung in more severe grades of pancreatitis. These findings provide a basis for the pathophysiologic production of cytokines and oxygen free radicals, which potentiate organ injury in severe pancreatitis. This study validates a new tool to study local and systemic effects of leukocytes in pancreatitis as well as new therapeutic hypotheses.

Technetium-99m-labeled chemotactic peptides: comparison with indium-111-labeled white blood cells for localizing acute bacterial infection in the rabbit.

The biodistribution and infection imaging properties of 99mTc-labeled formyl-methionyl-leucyl-phenylalanyl-lysyl-hydrazinonicotinamide (99mTc-HP) were compared with 111In-labeled leukocytes (111In-WBCs) in rabbits with E. coli infections. Groups of six animals were co-injected with 1 mCi of 99mTc-HP plus 0.05 mCi of 111In-WBCs and serial scintigrams were acquired from 3 to 6 hr and 18 hr postinjection. After acquiring the final images, the animals were killed and biodistribution was determined. At all imaging times, the distributions of 99mTc-HP and 111In-WBCs were similar and the sites of infection were well visualized with both radiopharmaceuticals. The target (infected muscle) to background (contralateral normal muscle) ratios (T/B) were: 3.38 +/- 0.46, 3.80 +/- 0.37 and 10.87 +/- 1.44 for 99mTc-HP and 1.71 +/- 0.04, 1.81 +/- 0.26 and 3.79 +/- 0.83, for 111In-WBCs at 3, 6 and 18 hr postinjection, respectively. The average ratio of T/B ratios (99mTc-HP-to-111In-WBCs) was 2.99 +/- 1.88, with no value less than unity. T/B ratios calculated from direct tissue sampling were significantly higher for 99mTc-HP than for 111In-WBCs (33.6:1 versus 8.1:1, p < 0.01). These differences were primarily due to increased absolute accumulation of 99mTc-HP (0.102%ID/g versus 0.024%ID/g, p < 0.01) in infected muscle rather than a difference in accumulation in normal skeletal muscle. These results indicate that 99mTc-HP yields target-to-background ratios greater than or equal to those achievable with 111In-WBCs probably as a result of an increase in absolute accumulation at the site of infection.

Localization of indium-111-immunoglobulin G, technetium-99m-immunoglobulin G and indium-111-labeled white blood cells at sites of acute bacterial infection in rabbits.

Biodistribution and infection imaging properties of 111In-DTPA-IgG, 99mTc-hydrazino nicotinamide-IgG and 111In-WBC were compared in rabbits with E. coli infection. Groups of six rabbits were injected with 10 mCi of 99mTc-IgG plus 0.5 mCi of 111In-IgG or 1 mCi of 99mTc-IgG plus 0.05 mCi of 111In-WBC. At 4-5 and 18-20 hr, dual photon scintigrams were acquired. At both times, the distributions of 99mTc and 111In-IgG were nearly identical. The sites of infection were well visualized with all three radiopharmaceuticals. In the early images, the target-to-background ratios (T/B) for 111In and 99mTc-IgG determined by ROI analysis were 1.95 +/- 0.26 and 2.57 +/- 0.38 (p = NS). In the delayed images, the T/B ratios increased (p < 0.01) to 3.56 +/- 0.49 and 4.90 +/- 0.98. At both times, the T/B ratios for 111In-WBC were higher (p < 0.01); 4.17 +/- 0.78 at 4-5 hr and 8.52 +/- 1.52 at 18-20 hr. These results indicate that all three agents yield excellent images of infection sites. Although 111In-WBC had higher T/B ratios, the ease of preparation of the radiolabeled proteins makes them attractive alternatives for infection imaging.

Noninvasive, real-time monitoring of renal function: the ambulatory renal monitor.

The objective of this study was to develop a method for the noninvasive, continuous and real-time monitoring of renal function. A radiation detector attached to a miniature data logger was used to monitor the clearance of the glomerular filtration agent 99mTc-diethylenetriaminepentaacetic acid from the extracellular space. The rate constant (k) for this clearance showed an excellent correlation with simultaneous glomerular filtration rate (GFR) measurements performed with a standard 125I-iothalamate clearance technique in 50 patients. Moreover, the reproducibility of the k measurement for an individual or a population was superior to the GFR measurement performed with the standard clearance technique. The procedure was also used to monitor the renal function in patients at risk for acute renal failure during angiography or in the intensive care unit under noninvasive and near real-time conditions. The results show that the technique detects rapid changes in renal function with a resolution time of 5 min in patients with normal renal function and 15 min in patients with severely impaired renal function. Since the method is noninvasive, precise and provides a near real-time measurement of GFR, its use may lead to an improvement in the management of patients in situations in which a rapid measurement is the major concern.

Serial analysis of renal blood flow by positron tomography with rubidium-82.

To determine whether renal blood flow can be measured by positron-emission tomography (PET) during constant infusion of rubidium-82 (82Rb) using a steady-state kinetic model, studies were performed in 10 dogs at control (n = 10), during mild flow reduction (n = 7), during severe flow reduction (n = 10), and after reperfusion of the kidney (n = 3). PET data were quantified to determine mean concentration of 82Rb (Ct) in each transverse section of the kidney. The arterial concentration (Ca) of 82Rb was measured by well counting of arterial blood samples during the equilibrium scan. 82Rb renal uptake (Ct/Ca) correlated nonlinearly with microsphere renal blood flow according to a steady-state kinetic model (r = 0.90). 82Rb estimated flow was 3.16 +/- 1.36 ml X min-1 X g-1 at control and 1.56 +/- 0.57 and 0.37 +/- 0.59 during mild and severe flow reductions, respectively. Microsphere determined flow was 2.89 +/- 0.77 ml X min-1 X g-1 at control, 1.58 +/- 0.42 at mild reduction, and 0.27 +/- 0.49 at severe reduction. In the occlusion and reperfusion model, the 82Rb estimated flow during occlusion was 0.21 +/- 0.15 ml X min-1 X g-1 and on reperfusion went up to 2.13 +/- 1.08. The contralateral kidney demonstrated reductions in the 82Rb estimated flow of 3.02 +/- 1.62 ml X min-1 X g-1 (63%) and 2.92 +/- 0.89 (61%) during mild and severe flow reductions, respectively. We conclude that PET with 82Rb permits serial quantitative assessment of renal flood flow.