Biodistribution in rats of 99Tcm-labelled human serum albumin

Three different 99Tcm-human serum albumin (HSA) preparations were simultaneously studied by high pressure liquid chromatography (HPLC) and gamma camera techniques in rats. The products contained variable amounts of 99Tcm-human albumin, 99Tcm-tin colloid and a 99Tcm-low molecular weight complex. The biological half life varied from 55 to 132 min and the bladder excretion for the first 60 min from 2 to 31%. Separated HPLC fractions of 99Tcm-albumin and 99Tcm-tin colloid both showed considerably longer biological half life when injected separately than when injected in the unfractionated preparation. A final evaluation of the quality of such products seem to require evaluation in humans.     

Imaging diagnosis of protein-losing enteropathy by 99mTc-labeled serum albumin

Abdominal scintigraphy with intravenous injection of 99mTc-labeled serum albumin was performed in 6 patients with protein-losing enteropathy (PLE) and 3 patients with non-gastrointestinal tract disorders. In 3 out of 6 patients with PLE, abnormal radioactivity was observed in the ileum region 3 hours after injection, and thereafter clear colon image was obtained. In the remaining 3 patients, the colon was visualized 24 hours after injection. On the other hand, in all patients with non-gastrointestinal tract disorders, no abnormal radioactivity was observed in the abdomen until 24 hours after injection. These results indicate that gastrointestinal protein loss could be demonstrated by scintigraphy with intravenously administered 99mTc-labeled serum albumin. In one healthy subject, 99mTc-labeled serum albumin was administered orally and abdominal scintigraphy was performed. Gastrointestinal tract image was only observed and no other image was demonstrated until 24 hours after oral administration. This result suggests that 99mTc excreted into the gastrointestinal tract is not reabsorbed. Therefore, abdominal scintigraphy with 99mTc-labeled serum albumin appears to be a simple and useful method for diagnosis of PLE.     

An integrated approach to biodistribution radiation absorbed dose estimates

An integrated approach to existing methods of extracting biodistribution data, pharmacokinetics and radiation absorbed dose estimates from serial scintigraphic images is described. This approach employs a single computer-generated user interface to reformat planar scans into a standard file type, align conjugate (anterior and posterior) images, draw regions of interest (ROIs) over selected organs and lesions and generate count data for anterior and posterior views and calculated geometric means. Using standard correction methods, the fraction injected activity is obtained for all ROIs and total body. This methodology has been applied to the analysis of indium-III-labelled breast-cancer-directed antibodies and technetium-90m-labelled CEA-specific antibody fragments in non-small-cell lung cancer. It is anticipated that this approach will be useful for evaluating the dosimetry of other radiolabelled monoclonal antibodies, as well as other radiopharmaceuticals.     

Gel-chromatographic analysis of 99mTc-labeled human serum albumin prepared with Sn(II) as the reductant

The labeling of human serum albumin (HSA) with 99mTc using Sn(II) as the reductant has been reinvestigated in view of the possibility of formation of Sn-Tc colloids. Preparations of 99mTc-HSA and mixtures of 99mTc-TcO-4 with Sn(II)Cl2 have been analyzed by means of gel chromatography using various gel matrices and eluents. No Sn-Tc colloids could be eluded from samples of 99mTc-HSA preparations. The percentage of labeling was about 90%. A comparative investigation of a number of gel-chromatographic systems for the detailed analysis of 99mTc-HSA has been made. It is found that a long column with Sephadex G-200 gives the best results.     

99mTc-labeled macroaggregated albumin in intrahepatic arterial chemotherapy

One hundred eighty-four 99mTc-labeled macroaggregated albumin (99mTc-MAA) perfusion studies were carried out in 39 patients with histologically proven primary (four) and metastatic (35) hepatic neoplasms. Three different patterns of tumor perfusion were observed: (1) increased central radioactivity (33%); (2) decreased central radioactivity (33%); and (3) mixed and/or diffuse radioactivity (33%). Extrahepatic perfusion as evidenced by radioactive localization in the region of the stomach, pancreas, and small bowel was noted in 51%. Its presence was associated with a higher incidence of gastrointestinal complications (45% vs. 16%). Tumor arteriovenous shunting was demonstrated in 38%, showing localization of radiotracer activity in the lungs, and decreased as tumors decreased in size. The use of 99mTc-MAA infusion studies in intrahepatic arterial chemotherapy offers an excellent evaluation of catheter placement and tumor perfusion, in addition to helping to avoid gastrointestinal complications.     

Biodistribution, radiation dose estimates, and in vivo Pgp modulation studies of 18F-paclitaxel in nonhuman primates.

Multidrug resistance (MDR) associated with increased expression and function of the P-glycoprotein (Pgp) efflux pump often causes chemotherapeutic failure in cancer. To provide insight into both the dynamics of the pump and the effects of MDR, we radiolabeled paclitaxel, a substrate for the Pgp pump, with (18)F to study MDR in vivo with PET. We obtained biodistribution and radiation dose estimates for (18)F-paclitaxel (FPAC) in monkeys and studied the effects of a Pgp blocker (XR9576, tariquidar) on FPAC kinetics. METHODS: Paired baseline and Pgp modulation (2 mg/kg XR9576) 4-h whole-body dynamic PET scans were obtained in 3 rhesus monkeys after injection of FPAC. Measured residence times were extrapolated to humans and radiation dose estimates were obtained using MIRDOSE3.1. The postmodulator area under the time-activity curves (AUCs) and Logan plot slopes, a measure of tracer distribution volume (equilibrium tissue-to-plasma ratio) that is inversely proportional to tracer efflux, were compared with baseline values to determine changes in FPAC distribution. RESULTS: Cumulative activities of the organs sampled accounted for 80% of the injected dose. The critical organ is gallbladder wall (0.19 mGy/MBq [0.69 rad/mCi]), followed by liver (0.14 mGy/MBq [0.52 rad/mCi]); the effective dose is 0.022 mSv/MBq (0.083 rem/mCi). XR9576 preinfusion changed the Logan plot slope for liver by +104% (P = 0.02), lung by +87% (P = 0.11), and kidney by -14% (P = 0.08). Changes in the mean AUC (normalized to the plasma AUC) were +54% (P = 0.08), +97% (P = 0.04), and -12% (P = 0.02), respectively, for liver, lung, and kidney. No significant difference was found in the metabolite-corrected plasma AUC (normalized to the injected dose) between the baseline and XR9576 modulator studies (P = 0.69). CONCLUSION: Under Radioactive Drug Research Committee guidelines, 266 MBq (7.2 mCi) FPAC can be administered to humans up to 3 times a year. The increase in FPAC accumulation in liver and lung after XR9576 is consistent with Pgp inhibition and demonstrates the potential of FPAC to evaluate MDR.     

Organ and fetal absorbed dose estimates from 99mTc-sulfur colloid lymphoscintigraphy and sentinel node localization in breast cancer patients.

The purpose of this retrospective study was to determine whether lymphoscintigraphy (LSG) for sentinel lymph node (SNL) mapping in a woman with a breast mass presents an unacceptable risk to her fetus. We assessed radiation-absorbed dose to various organs from 99mTc-sulfur colloid (TSC) LSG using standard internal absorbed dose assessment methodologies for both reference phantoms as well as for phantom models using the specific patient population characteristics such as total body and injected organ mass. The study also projected the radiation-absorbed dose to the fetus from LSG for SLN mapping. METHODS: Data from 1,021 nonpregnant women with early-stage breast cancer who underwent SLN mapping and biopsy procedures were analyzed. Patients had a single-site intradermal injection of unfiltered TSC in 0.05 mL normal saline: 3.7 MBq (0.1 mCi) on the morning of surgery (1-d protocol) or 18.5 MBq (0.5 mCi) on the afternoon before surgery (2-d protocol). A standard internal dose calculation methodology was used to calculate absorbed doses to various organs and to a modeled fetus at 3-, 6-, and 9-mo gestation from the injection site as well as from systemic activity. RESULTS: The highest estimated absorbed doses were observed for the reference 9-mo-pregnant model under the 2-d protocol. Absorbed doses of 14.9, 0.214, 0.062, 0.151, 0.004, 0.163, 0.075, and 0.014 mGy were received by the injected breast, heart, liver, lung, ovaries, thymus, total body, and fetus, respectively. Effective doses from the 2-d protocol were estimated to be 0.460, 0.186, and 0.245 mSv for the reference population, the total Memorial Sloan-Kettering Cancer Center (MSKCC) study patient population, and childbearing-age MSKCC patient population (i.e., <45 y old), respectively. CONCLUSION: SLN procedures lead to a negligible dose to the fetus of 0.014 mGy or less. This is much less than the National Council on Radiation Protection and Measurements limit to a pregnant woman. Calculations using actual patient population characteristics resulted in lower organ dose estimates than more conservative reference models.     

Detection of rhinoliquorrhea with 99mTc-labelled human serum albumin

99mTc-labelled human serum albumin was used in 42 patients, 35 without and 7 with proven rhinoliquorrhoea, to combine liquor scintigraphy with the detection of liquor fistula. Since some 99mTc is split off from albumin during the time of investigation and is actively secreted by mucous membranes and salivary glands it was not possible to detect liquorrhoea by calculation of activity ratios like that of secretion of the nose to blood or saliva. But dividing the activity in the secretion of the nose by that in saliva after 2 and 6 hrs this ratio was independent of the amount of activity and had a sensitivity of 100% and a specificity of 93% in detecting a liquor fistula. Combining scintigrams of the subarachnoidal space with the search for liquorrhoea using an always available radiopharmaceutical such as labelled HSA might be attractive. In 4 of 7 patients with a liquor fistula there was additionally a pathologic result obtained with scintigraphy of the subdural space.     

Radiation absorbed dose from technetium-99m DTPA

The whole-body retention of intravenously administered [99mTc]DTPA was measured by urine analysis and whole-body counting in eight normal subjects. On average, the elimination of [99mTc]DTPA was faster in these subjects than in 11 patients under study for hypertension whose whole-body retention data were used in MIRD Dose Estimate Report No. 12. The average residence time for [99mTc]DTPA in total body, less bladder contents, was only 65% of the MIRD value. However, despite this difference, the dosimetry is similar in both cases largely owing to the influence of radioactivity in bladder contents. Approximately 2-3% of the administered radioactivity was retained in the body for a time that was long relative to the physical half-life of 99mTc, and probably reflects a small amount of protein binding of the DTPA preparation.     

Biodistribution and radiation dosimetry of stabilized 99mTc-exametazine-labeled leukocytes in normal subjects.

Labeling leukocytes with 99mTc-exametazime is a validated technique for imaging infection and inflammation. A new radiolabeling technique has recently been described that enables leukocyte labeling with a more stable form of 99mTc-exametazime. A normal value study of stabilized 99mTc-exametazime-labeled leukocytes has been performed, including biodistribution and dosimetry estimates in normal subjects. METHODS: Ten volunteers were injected with stabilized 99mTc-exametazime-labeled autologous leukocytes to study labeled leukocyte kinetics and dosimetry in normal subjects. Serial whole-body imaging and blood sampling were performed up to 24 h after injection. Cell-labeling efficiency and in vivo viability, organ dosimetry, and clearance calculations were obtained from the blood samples and imaging data as well as urine and stool collection up to 36 h after injection. RESULTS: Cell-labeling efficiency of 87.5% +/- 5.1% was achieved, which is similar to or better than that reported with the standard preparation of 99mTc-exametazime. In vivo stability of the radiolabeled leukocytes was also similar to in vitro results with stabilized 99mTc-exametazime and better than previously reported in vivo stability for nonstabilized 99mTc-exametazime-labeled leukocytes. Organ dosimetry and radiation absorbed doses were similar with a whole-body absorbed dose of 1.3 x 10(-3) mGy/ MBq. Urinary and fecal excretion of activity was minimal, and visual assessment of the images showed little renal parenchymal activity and no bowel activity up to 2 h after injection. CONCLUSION: Cell labeling and in vivo stability appear improved compared with the leukocytes labeled with the nonstabilized preparation of 99mTc-exametazime. There are advantages in more cost-effective preparation of the stabilized 99mTc-exametazime and an extended window for clinical usage, with good visualization of abdominal structures on early images. No significant increase in specific organ and whole-body dosimetry estimates was noted compared with previous estimates using nonstabilized 99mTc-exametazime-labeled leukocytes.     

Measurement of absorbed dose and proposed radiation exposure level

Absorbed dose was measured in clinical X-ray examinations using TLD. Moreover, we distributed the levels of radiation exposure into 3 classes. The presumed dose of the internal organs, e.g., uterus dose, was computed to depth doses with a surface dose. This information provides a prediction of the influence of radiation, and the examination can be performed with the informed consent of the patient. Moreover, we examined the distribution of the level of absorbed dose. We proposed two kinds of radiation exposure level, one to the fetus in a pregnant woman and a general level of radiation exposure that is not applied to pregnant women. The levels were as follows: 0.5 mGy and 100 mGy were considered the boundaries for fetal radiation exposure in a pregnant woman, and 200 mGy and 3 Gy were considered the boundaries for the general level of radiation exposure (excluding pregnant women).     

Bone accumulation of 99mTc-labeled leucocytes.

Leucocytes were separated from rats' blood by dextran sedimentation method and labeled with 99mTc-pertechnetate. A maximum labeling efficiency of 18.5% was achieved with the addition of 1 mg of stannous chloride. The labeled leucocytes were intact and viable and the 99mTc label was firm. Distribution studies in rats, 3 hr after injection of 99mTc-labeled leucocytes, showed 33% concentration in the mineral part of the bone, this being slightly lower than the 36.8% concentration in the liver. Technetium concentration in the bones due to a complex formed by various ingredients used for leucocyte labeling was excluded since negligible bone uptake was noted after injection of an incubated mixture of 99mTc and all ingredients except leucocytes. Also 51Cr-labeled leucocytes showed no localization in the bone. These studies indicate that 99mTc and intact leucocytes form some sort of complex which has an affinity for bone cortex.