Anthony R. Benedetto

Enhanced drug retention in VX2 tumors by use of degradable starch microspheres.

Twenty-nine rabbits with 12- to 14-day-old VX2 tumors in the hind leg were injected intraarterially with technetium-99m (99mTc) DTPA and various combinations of biodegradable starch microspheres, Spherex (Pharmacia, Sweden), to evaluate the efficacy of the microspheres in enhancing tumor retention of 99mTc DTPA. A gamma camera and nuclear medicine computer were used to generate time activity curves of 99mTc DTPA concentration in the tumors. Blood flow to the tumor and various muscles was also measured at intervals by left ventricular injection of 15 micron radiolabeled plastic microspheres. Ninety minutes following the administration of 99mTc DTPA, specimens from the tumor, plasma and different muscles were counted in a NaI well counter connected to a multichannel analyzer. When biodegradable microspheres mixed with 99mTc DTPA were injected and followed by a slow infusion of plain starch microspheres, the 99mTc DTPA was retained in the tumor at concentrations up to 11 times that seen when 99mTc DTPA alone was injected; the corresponding biological half-time was 13 times longer than control values. Additionally, the degree of drug retention was inversely related to blood flow, with retention increasing as blood flow decreased. The results have possible applications to the use of biodegradable microspheres in the intraarterial delivery of chemotherapeutic agents to solid tumors.

Intravascular Hemolytic Transfusion Reaction without Detectable Antibodies: A Case Report and Review of Literature

Abstract. A case of intravascular hemolytic transfusion reaction without detectable antibodies occurring in a 55‐year‐old male is reported. Specificity for the C antigen in the Rh system was demonstrated by technetium‐99m red cell survival studies. A cell‐mediated mechanism of hemolysis was suspected and investigated. Previously reported cases are reviewed and discussed. The entity of intravascular hemolytic transfusion reaction associated with minimal symptoms and no detectable antibodies deserves further investigation.

Failure of quality control to detect errors in the preparation of technetium-99m disofenin (DISIDA)

Uptake of Tc-99m disofenin is so strongly hepatobiliary that striking appearance of radioactivity in the reticuloendothelial system (RES) is almost certainly caused by improper preparation of the disofenin kit. Four patients who received injections of Tc-99m disofenin demonstrated a pronounced RES biodistribution in addition to the expected hepatobiliary pattern. Since routine quality control testing had not forewarned us of this gross lack of radiochemical purity, Tc-99m disofenin kits were subjected to a variety of insults to elucidate the mechanisms of quality control failure. Assessment of radiochemical purity was conducted using instant thin-layer chromatography (ITLC) and two solvent systems. We concluded that both Tc-99m pertechnetate and Tc-99m sulfur colloid had been injected into the cold disofenin kit. Visual inspections were not reliable for verifying the final radiopharmaceutical product because of dilution of the sulfur colloid by pertechnetate. ITLC testing failed because the assay method being used at that time did not accurately assess the hydrolyzed fraction (colloidal component). Recommendations are made to preclude recurrence of the errors that occurred.

Population exposure from nuclear medicine procedures: measurement data

In order to estimate the public radiation burden from nuclear medicine studies, a TLD chip in a sealed plastic bag was taped on the abdomen of patients who received 111In as chloride or oxine, 201T1 chloride, or one of four common 99mTc agents. The TLD chip was removed after 24 h. Additionally, abdominal skin surface exposure rate measurements were performed with an ionization chamber survey meter at various times (0 to about 60 h). There was superb correlation between TLD and integrated exposure rate measurements and between TLD and ionization chamber measurements and MIRD calculated doses. Scenarios postulated for exposure of co-workers and family members yielded doses between 7 muSv (0.7 mrem) and 20 muSv (2 mrem) for the selected radiopharmaceuticals. Calculations of the total population exposure from nuclear medicine procedures indicate the per capita dose (amortized over the entire population) is approximately 0.4 muSv (0.04 mrem), a negligible dose compared to natural background and total medical irradiation.

A technique for the preparation of Tc-99m red blood cells for evaluation of gastrointestinal hemorrhage.

Tc-99m labeled red blood cell (RBC) preparations are gaining wide acceptance in the diagnosis and localization of gastrointestinal bleeding. A major requirement of the radiopharmaceutical is that the percentage of Tc-99m attached to red cells in the injected dose must be extremely high, since free pertechnetate is secreted into the gastrointestinal tract and may obscure a bleeding site. We have developed a combined in vivo/in vitro labeling procedure which is simple and rapid, and which enables the administration of substantial amounts of RBC-bound Tc-99m and minimizes the amount of unbound technetium present. The technique is readily utilizable in any nuclear medicine clinic and requires no investigative pharmaceuticals.

Patterns of intestinal activity with Meckel's scintigraphy

Three patterns of intestinal activity were noted in a review of 64 patients studied with Tc-99m sodium pertechnetate for suspected Meckels diverticulum: no bowel activity seen (37.5%), bowel activity visualized after stomach activity (39.1%), and diffuse bowel activity seen simultaneously with stomach activity (23.4%). The latter pattern, which is relatively common, could mask a true Meckels diverticulum and lead to either a false-negative or indeterminate diagnosis. A series of 10 dogs was also studied to evaluate the effects of fasting and feeding on the intestinal pattern. No definite relationship was observed.

Tc-99m red blood cells for the study of rapid hemolytic processes associated with heterologous blood transfusions.

Chromium-51 labeled erythrocytes (Cr-51 RBC) are suitable for the study of hematologic disorders which involve relatively slow destruction of circulating erythrocytes, taking several days to several weeks. However, Cr-51 RBC are not suitable for investigating rapid hemolytic processes which occur within a matter of a few hours due to the variable and unpredictable elution of Cr-51 from the erythrocytes during the first 24 hours or so (1). Imaging, which could be useful in identifying organ systems involved in the hemolytic process, cannot be performed with Cr-51 RBC because of the high dose commitment caused by the low yield of gamma rays from Cr-51 (2). A method of labeling RBC with Tc-99m, which results in a radiopharmaceutical that combines the excellent dosimetric and imaging qualities of Tc-99m with an extremely stable bond between the Tc-99m and the RBC, is reported. The successful application of this technique in providing red cell support for a cancer patient with an unusual history of intravascular hemolytic transfusion reactions is also reported.

Verification of global cerebral ischaemia using scintigraphy

The induction of global cerebral ischaemia in laboratory animals is difficult to accomplish and has been even more difficult to verify. Most reported verification methods suffer from lack of sensitivity or from being traumatic and highly invasive. We describe a non-traumatic global cerebral ischaemia verification technique which is quantitative, simple, and highly sensitive. Radioactive technetium-99m pertechnetate is injected intravenously during the ischaemic phase of an experiment and the appearance of radioactivity within the animals head is quantitated using a gamma camera and nuclear medicine computer. Radioactivity levels below the visual perception threshold are readily measured, thus providing a high degree of confidence in assessing the partial or total nature of cerebral ischaemia.

A mathematical index of uniformity (IOU) for sensitivity and resolution.

The authors define a mathematically precise index of uniformity (IOU) and show that the IOU is a convenient tool to quantitate uniformity of sensitivity and resolution response for any given area of interest on the detector face. They also show that the IOU is an appropriate factor for weighing the mean values of sensitivity and resolution for nonuniformity of response; these weighted sensitivity and resolution factors are used to derive a weighted figure of merit which takes into account, in a single parameter, the nonuniformities of response inherent in the determination of sensitivity and resolution.