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The biokinetics of inert lymphoscintigraphic agents strongly depends on their particle size. Different techniques for characterization of colloids are discussed. Experiments have been performed on eight different colloids. The particle size has been investigated with scanning electron microscopy. Activity distributions have been obtained with ultrafiltration and gel-column scanning technique. The colloids suggested for lymphoscintigraphy were found to have a median size of about 40-50 nm except one minimicro-aggregated human serum albumin colloid which has a median particle size around 10 nm. The biokinetics were studied with a scintillation camera in rabbits after a subcutaneous injection. Time-activity curves were generated. After 5 hr the rabbits were dissected and the activity content in different tissues measured. A compartment model for the biokinetics was designed and rate constants evaluated. The total and specific activity uptake in parasternal lymph nodes was highest for the small-particle colloids. The compartment model showed a good fitting to the experimental data.

Hepatic reticuloendothelial function was measured in 6 experimental groups of rats with various portasystemic shunts or total liver arterialization by computer calculation of the hepatic uptake rate of intravenously injected 99mTc-sulphur colloid. Marked reduction of the hepatic reticuloendothelial system (RES) function was found both 1 and 3 weeks after the construction of a mesentericocaval or conventional end-to-side portacaval shunt. Hepatic RES function was also lowered both 1 and 3 weeks after a modified portacaval shunt, but the reduction was much less pronounced. Total liver arterialization produced a similar mild reduction of hepatic RES function after 1 week; however, there was no longer any significant reduction after 3 weeks. This study concludes that total liver arterialization ameliorates the negative effect that portasystemic shunting has on hepatic RES function.

Increased fecal blood loss was produced in healthy volunteers by the administration of two nonsteroidal anti-inflammatory drugs (NSAID), naproxen or fenflumizole. Basal as well as drug-induced gastrointestinal blood loss was measured using 51Cr erythrocyte labeling. Median rise in daily fecal blood loss was 432%. All subjects were endoscoped at the initiation and at the completion of the study. Endoscopic findings were assessed quantitatively by two observers in two different ways. All subjects but three had gastric mucosal lesions at follow-up endoscopy. There was a good correlation between the endoscopic assessments but no statistical correlation between the endoscopic assessment and the increase in fecal blood loss. The data suggest that factors other than gastric mucosal lesions have to be taken into account when investigating NSAID-induced gastrointestinal bleeding.

Lymphoscintigraphy using 99mTcSb2S3 colloid was performed in 32 patients with malignant melanoma. Subcutaneous injections were made peritumorally in 20 patients and dorsopedally in 12 patients. Regional lymph node dissections were carried out on the following day in 16 patients and the resected lymph nodes were weighted, measured for radioactivity, and examined by light microscopy. Lymph flow to regional lymph nodes was shown in all but 2 patients. Twenty-nine of 239 lymph nodes contained metastases. Radioactivity was demonstrated in 17 of these nodes. In 5 of 11 patients with metastatic disease, the highest uptake was found in cancerous lymph nodes. The specific activity-uptake distribution in isolated ilio-inguinal lymph nodes after a dorsopedal injection was log-normal with a mean of 0.05%/g indicating a good saturation of colloid particles. This investigation concludes that the observed lymph flow directions in patients injected peritumorally are of value for the follow-up. Quantitative lymphoscintigraphy in patients with melanoma of the lower extremities is, however, of no value for excluding ilio-inguinal lymph node metastases.

A quantitative kinetic technique using a scintillation camera has been developed for investigating lymph drainage and the uptake in the lymph nodes of 99mTcSb2S3 colloid injected subcutaneously. Twenty-two patients with primary malignant melanoma were examined. Lymph-node dissection was performed and 185 lymph nodes were individually measured for radioactivity. The kinetics of colloid uptake in individual nodes can be expressed by a simple two-compartment model. The outflow of colloid from the injection site was found to be monoexponential, and the tissue volume containing the injected colloid at the injection site increased asymptotically with time. A model has been developed for calculating absorbed doses at the injection site and in organs with colloid uptake. The following absorbed doses were estimated (muGy/MBq): whole body 0.7-4.5, gonads 0-22, liver 1.0-3.9, lymph nodes up to 1000 and injection site about 10,000. Possible biological effects in the skin and effective dose equivalents have been estimated when using other lymphoscintigraphic agents.

The [99mTc]sulfur colloid distribution in rat organs was investigated after the administration of different amounts of colloid particles. Saturation of the liver and spleen was not observed. Blood clearance was significantly reduced 15 min after injection above approximately 3 X 10(9) particles per kg body weight. With an increasing number of injected particles, lung uptake increased and bone marrow uptake decreased. Microfiltration studies showed that the colloid is unaffected by dilution with saline but may be affected after incubation in normal rat plasma. We conclude that the distribution of [99Tc]sulfur colloid in organs varies with the number of injected particles and therefore, is not dependent upon the blood flow to the reticuloendothelial organs alone. The "critical colloid dose" may differ among the reticuloendothelial organs and cannot, therefore, be evaluated by blood clearance measurements alone. The considerable influence of the number of injected colloid particles on bone marrow uptake should also be recognized when carrying out dosimetric calculations.

The scintigraphic technique to investigate the lymphatic system is based on a good knowledge of basic criteria in order to correctly interpret the findings. This article penetrates these criteria, updates the present knowledge, and covers basic science work and clinical applications. The anatomy, physiology, and pathology of the lymphatic system are covered. Basic criteria for the radiopharmaceuticals to be used are described as well as their quality control. The principles for lymphoscintigraphy are described. The dosimetry in lymphoscintigraphy as well as radiation risk is estimated for different procedures. Experimental animal studies are summarized. Clinical applications cover staging procedures for breast cancer, malignant melanoma, pelvic neoplasms, and lymphoma. Lymphadenoectomy follow-up studies are also included. The use of lymphoscintigraphy in radiotherapy dose planning is described as well as lymphatic function studies in, e.g., edema and lymph transplantations.