Utility of whole gut transit scintigraphy in patients with chronic gastrointestinal symptoms.

BACKGROUND: To review our experience of doing whole gut transit scintigraphy in patients presenting with functional gastrointestinal problems and to determine its clinical usefulness. METHOD: All whole gut transit studies using a liquid meal over a 5-year-period were reviewed and clinical outcome assessed. RESULTS: Fifty-five patients (44 women; mean age 43 years) underwent whole gut transit scintigraphy using indium-111 diethylene triamine penta-acetic acid in water. The main symptoms were constipation (49%), dyspepsia (25%) and diarrhoea (25%). Colonic transit was delayed in 63% of patients with constipation, which was significantly (P=0.005) higher than that in patients with dyspepsia. Delayed colonic transit was also seen in 43% of patients with diarrhoea. Only 26% of patients with constipation had a delay in liquid gastric emptying and small bowel transit. Gastric emptying, small bowel transit and colonic transit were normal in 43, 79 and 29% of patients with dyspepsia, respectively. There was no statically significant difference in gastric emptying and small bowel transit between patients with constipation, diarrhoea and dyspepsia. CONCLUSION: Liquid-phase whole gut transit scintigraphy seems to be a useful investigation in patients with chronic gastrointestinal symptoms. Rational use of this modality may help the clinician change the management or better characterize the underlying problem/diagnosis in the majority of patients with functional symptoms.

Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity.

Alloimmune feto-maternal destruction of blood cells is thought to be mediated by binding of alloantibodies to Fc receptors on effector cells. Blocking the antigen using inert antibodies might prolong cell survival. We have performed a "proof of principle" study in volunteers to measure the intravascular survival of autologous red cells coated with human recombinant IgG antibody containing a novel constant region, G1Deltanab, devoid of in vitro cytotoxic activity. RhD-positive red blood cells (RBCs), labeled with chromium-51 or technetium-99m, were separately coated to equal levels with wild-type IgG1 or G1Deltanab anti-D antibody (Fog-1). After re-injection, there was complete, irreversible clearance of IgG1-coated RBCs by 200 minutes, concomitant with appearance of radiolabel in plasma. Gamma camera imaging revealed accumulation in spleen and, at higher coating levels, in liver. In contrast, clearance of G1Deltanab-coated cells was slower, incomplete, and transient, with whole blood counts falling to 7% to 38% injected dose by about 200 minutes before increasing to 12% to 67% thereafter. There was no appearance of plasma radiolabel and no hepatic accumulation. These findings suggest that G1Deltanab-coated RBCs were not hemolysed but temporarily sequestered in the spleen and that our approach merits investigation in larger studies.

Mechanism of accumulation of 99mTc-sulesomab in inflammation.

UNLABELLED: 99mTc-Sulesomab, the Fab fragment of anti-NCA-90, is used as an in vivo granulocyte labeling agent for imaging inflammation. It is not clear to what extent it targets cells that have already migrated into the interstitial space of an inflammatory lesion as opposed to circulating cells. The contribution to signal of radioprotein diffusion in the setting of increased vascular permeability is also poorly documented. METHODS: We compared the local kinetics of (99m)Tc-sulesomab and (99m)Tc-labeled human serum albumin (HSA), which have similar molecular sizes, in 7 patients with orthopedic infection proven by clearly positive (111)In-leukocyte scintigraphy. (99m)Tc-Sulesomab and (99m)Tc-HSA were administered in sequence separated by an interval of 2-6 d. Images were obtained 1, 3, 4, and 6 h after injection, and multiple venous blood samples were obtained for blood clearance measurement. Patlak-Rutland (P-R) analysis was performed to measure lesion and control tissue protein clearance. Target-to-background tissue (T/Bkg) ratios were calculated for each radioprotein and compared with the T/Bkg ratio for (111)In-leukocytes. (99m)Tc-Sulesomab binding to granulocytes was measured in vitro and ex vivo and to primed and activated granulocytes in vitro. RESULTS: After intravenous injection, <5% of the circulating radioactivity was cell bound with both radioproteins so that the P-R curves could therefore be assumed to represent extravascular uptake of free protein. The blood clearance (mean +/- SD) of sulesomab was 23.4 +/- 11.7 mL/min, approximately 5 times greater than that of HSA, for which it was 4.8 +/- 3.1 mL/min. Likewise, clearance into the lesion of sulesomab was consistently higher than that of HSA, on average about 3 times as high. Nevertheless, the T/Bkg ratios for sulesomab and HSA were similar, except at 6 h when that of HSA (2.14 +/- 0.6) was higher than that of sulesomab (1.93 +/- 0.5; P approximately 0.01). Both values were considerably less than the T/Bkg ratio on the (111)In-leukocyte images, which, at 22 h, was 12.3 +/- 5.3. Moderate clearance of sulesomab, but not HSA, was seen in the control tissue. Granulocytes bound significantly more (99m)Tc-sulesomab in vitro when primed or activated. CONCLUSION: (a) Sulesomab does not localize in inflammation as a result of binding to circulating granulocytes; (b) sulesomab is cleared into inflammation nonspecifically via increased vascular permeability; nevertheless, it may be cleared after local binding to primed granulocytes or bind to activated, migrated extravascular granulocytes; and (c) HSA produces a similar or higher T/Bkg ratio than sulesomab because sulesomab is cleared into normal tissues and because image positivity in inflammation is significantly dependent on local blood-pool expansion.