Scintigraphic assessment of interdigestive duodenogastric reflux in humans: distinguishing between duodenal and biliary reflux material.

BACKGROUND: Late duodenal phase III is characterized by retroperistalsis. The physiologic function of this phenomenon is unknown. Our aim was to study the relationship between duodenal motility and the transport of duodenal contents from the biliary tract and the duodenum by using a double-isotope technique. METHODS: Manometric analysis of the direction of interdigestive duodenal pressure waves was performed in 12 volunteers. Duodenal marker was infused directly into the proximal duodenum, and bile marker was infused intravenously for 2 h. Radionuclide activity was examined for regions corresponding to the stomach, gallbladder, and duodenum. RESULTS: In phase II, antegrade pressure waves dominated with propulsion of both markers to the jejunum. Retroperistalsis occurred in 90% of the activity fronts and was always (100%) followed by retropulsion of duodenal marker to the stomach. A clear-cut reflux of bile marker was seen in only 17% of the activity fronts. The incidence rate of duodenogastric reflux was highest in phase III (P=0.008) compared with phase II with an infrequent (P=0.002) admixture of bile. Bile marker contents increased abruptly in the gallbladder during phase III. CONCLUSIONS: Late phase III acts as a retroperistaltic pump, retropelling duodenal contents to the stomach. In this physiologic duodenogastric reflux. bile is avoided by deviation to the gallbladder, probably by a phase lll-associated occlusion of the sphincter Oddi.

Assessment of gastric emptying: comparison of solid scintigraphic emptying and emptying of radiopaque markers in patients and healthy subjects.

The gold standard for measuring gastric emptying is scintigraphy, either with digestible solids or liquids. Unfortunately, this method is expensive and of limited availability. An alternative could be to use radiopaque markers (ROMs). Our aim was to compare these two tests in healthy volunteers and in patients to see whether emptying of ROMs can substitute for scintigraphic solid emptying. We also intended to see if patients with small intestinal bacterial overgrowth (SIBO) had delayed gastric emptying. Twenty healthy subjects and 21 patients, 11 with SIBO and 10 with insulin-dependent diabetes mellitus (IDDM), were included. A standard meal with a [99mTc]MAA-labeled omelet and 20 ROMs was given. Scintigraphic emptying and ROM emptying were followed simultaneously. Reference values for gastric emptying of ROMs were determined in 50 healthy subjects. The scintigraphic method and the radiologic method correlated significantly in healthy subjects (P < 0.05), and in patients (P < 0.001), when comparing half-emptying time for both methods. Scintigraphic half-emptying time correlated significantly with emptying of ROMs after 6 hr. Six of 11 patients with SIBO (P < 0.02) and 7/10 patients with IDDM (P < 0.02) had delayed scintigraphic emptying of solids using the 95th percentile in the controls as the upper reference value. Gastric emptying of ROMs was, similar to solid scintigraphic gastric emptying, slower in women than in men. In conclusion, scintigraphic emptying of solids and emptying of ROMs are closely correlated. The radiologic method can be used as a simpler and more readily available method. Women have slower gastric emptying of ROMs than men, which necessitates separate reference values. A high proportion of patients with symptomatic IDDM and with SIBO have delayed gastric emptying.

Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.

A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.

125I-labelling of an internally 75Se-labelled monoclonal antibody--biodistribution in tumour-bearing nude mice.

A monoclonal antibody, C215, was first internally labelled with 75Se-methionine and then labelled with 125I. The biodistribution of the dual-labelled [125I][75Se]C215 was studied in tumour-bearing nude mice killed 3 days after injection. The biodistribution of the dual-labelled [125I][75Se]C215 was compared with the biodistribution of single-labelled [131I]C215 and [75Se]C215. Iodine-labelled antibodies seem to be damaged during iodination, affecting the disappearance rate and tumour uptake. There were no signs of dehalogenation of circulating antibodies or antibodies taken up in the tumour.

Therapy with 125I-labelled internalized and non-internalized monoclonal antibodies in nude mice with human colon carcinoma xenografts.

The therapeutic effects of 125I-labelled (18-97 MBq) monoclonal antibodies (MAb) C-242, C-215 and S-S.1 were studied in nude mice with human colorectal adenocarcinoma tumours. The antibodies were administered 2 or 10-16 days after implantation of the tumour cells. The monoclonal antibody C-242 was internalized into the tumour cells, C-215 was internalized to a lower degree while S-S.1 (unspecific MAb) was not internalized at all. No enhanced therapeutic effect of 125I-C-242 was observed, as a result of Auger electrons, compared with 125I-C-215 and 125I-S-S.1.

Comparison of the biodistribution of 75Se- and 131I-labelled monoclonal antibodies in nude mice.

A monoclonal antibody, C-215, against colon cancer, was internally labelled with [75Se]methionine. The biodistribution was studied in tumour-bearing nude mice and compared with the biodistribution of [131I]C-215. The tissue uptake was divided into three parts: antibody bound to the antigen, antibody in the extracellular space and uptake of the released radionuclide. [75Se]C-215 showed a greater amount of antigen-bound antibody in the tumour, but also a greater unspecific uptake both in tumour and normal tissue.

Kupffer cell and hepatocyte function in rat transplanted liver.

The liver consists essentially of two compartments, parenchymal cells (PC) and non parenchymal cells (NPC) i. e. Kupffer cells, endothelial cells, fat storing cells and pit cells. PC remain after transplantation but NPC are eventually exchanged with host cells. Dynamic liver scintigraphy with albumin colloid, extracted by NPC, and IODIDA, extracted by PC, were tested to evaluate function as determined by clearance rates in these two cellular compartments. Experimental liver transplantation was performed in 15 syngeneic rats. Following transplantation, we performed dynamic liver scintigraphy with 0.5 ml 5 MBq 99mTc-Nanocoll and 0.5 ml 20 MBq 99mTc-IODIDA, 10 s per frame, 30 min for each examination. Percentage clearance rate, per minute was calculated from uptake curves over the liver. Uptake curves were nearly exponential and clearance rates could be estimated from a logarithmic plot of uptake versus time. The clearance rate was 25 +/- 4% per min (mean +/- SD) for NPC and 32 +/- 15% per min for PC in controls. After liver transplantation it was 31 +/- 7% per min for NPC and 30 +/- 15% per min for PC. Dynamic liver scintigraphy with 99mTc-Nanocoll and 99mTc-IODIDA alloweds a separate assessment of the function of PC and NPC after experimental liver transplantation in rats.

Comparison of seven iodine-labelled monoclonal antibodies in nude mice with human colon carcinoma xenografts.

The biokinetics of seven 131I-labelled monoclonal antibodies (MAbs), directed against human colon carcinoma and one 125I-labelled unspecific MAb have been examined. The study in nude mice, carrying human colon carcinoma, was intended to be a step in the selection of the most suitable antibody for clinical scintigraphy. The biological half-life in blood was found to be between 1.3 and 7.4 days for the different MAbs. Chromatography of plasma samples showed that the radioiodine was mainly bound to IgG-sized molecules. The (normal tissue)/blood ratios were similar for all the MAbs. The tumour/blood ratio was 0.41 for the unspecific MAb and 0.49-1.1 for the specific MAbs, and the tumour/muscle ratio was between 3.2 and 6.8 for the specific MAbs 6 days after injection. For one MAb tumour/blood and tumour/muscle ratios were 3.9 and 9.8 respectively 9 days after injection. Localization indices were at their highest 2.6 6 days after injection. For at least two of the monoclonal antibodies the tumour/blood and tumour/muscle ratios found are high enough to justify clinical trials regarding their usefulness for scintigraphy of colon cancer in man.

Vascular clearance by the reticuloendothelial system--measurements using two different-sized albumin colloids.

Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with 133Xe washout technique. The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08 +/- 0.05 vs 0.49 +/- 0.02 10(-2)s-1). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics of radioiodinated monoclonal antibodies in the rat. Influence of tumour growth and reticuloendothelial system host modulation.

This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour-associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour-associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour-bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results.