The use of TL detectors in dosimetry of systemic radiation therapy.

A method for determining absorbed doses to organs in systemic radiation therapy (SRT) is evaluated. The method, based on thermoluminescent (TL) dosimeters placed on the patient's skin, was validated and justified through a phantom study showing that the difference between measured (TL dosimeters in the phantom) and derived (TL method) values is within 10%. Six radioimmunotherapy (RIT) patients with widespread intraperitoneal pseudomyxoma were also studied. In dose evaluations, special emphasis was on kidneys. In addition to the TL method, the absorbed doses to kidneys were calculated using MIRD formalism and a point dose kernel technique. We conclude that in SRT the described TL method can be used to estimate the absorbed doses to those critical organs near the body surface within 50% (1 SD).

A dual-tracer method for studying intragastric distribution and gastric emptying of solids and liquids in functional dyspepsia.

Twenty-five patients with functional dyspepsia and 11 healthy controls matched for age and sex were examined. The patients were divided into two groups: patients with dysmotility-like symptoms and those with ulcer-like symptoms. In a dual-tracer gastric emptying study, dysmotility-like and ulcer-like symptoms could not be distinguished from each other on the basis of gastric emptying times. The intragastric distribution and the solid lag time in dysmotility-like dyspepsia differed significantly from those of the controls.

Kinetics of 111In-labeled bleomycin in patients with brain tumors: compartmental vs. non-compartmental models.

The kinetics of an indium-111 labeled bleomycin complex (111In-BLMC) after rapid intravenous injection in patients with brain tumors was quantified by using compartmental and non-compartmental models. The models were applied to data obtained from 10 glioma, one meningioma, and one adenocarcinoma brain metastasis patients. Blood and urine samples from all the patients and tumor samples from three patients were collected. The mean transit time of 111In-BLMC in the plasma pool was 14 +/- 7 min without and 1.8 +/- 0.6 h when accounting for recirculation, and 13 +/- 4 h in the total body pool. The mean plasma clearance of 111In-BLMC was 0.3 +/- 0.1 m/blood/min and the mean half-life in urine was 3.5 +/- 0.6 h. The mean transfer coefficients for the open three-compartmental model were: excretion from plasma = 0.02 +/- 0.01, from depot to plasma = (12 +/- 9)*10(-4), from plasma to depot = 0.01 +/- 0.01, from tumor to plasma = 0.39 +/- 0.19 and from plasma to tumor = 1.11 +/- 0.57, all in units minute-1. The mean turnover time from the tumor was 4.5 +/- 2.7 min and from the depot 20 +/- 8 h. It is concluded that both compartmental and non-compartmental models are sufficient to describe the kinetics of indium-111 labeled bleomycin complex. The non-compartmental model is more practical and to some extent more efficient in describing the in vivo behaviors of 111In-BLMC than the compartmental model. The compartmental model used provides estimates of both extraction and excretion from the plasma and tumor.

Effects of lithium gammalinolenate on the perfusion of liver and pancreatic tissues in pancreatic cancer.

Because of its poor prognosis, new modalities to treat pancreatic cancer are highly welcome. Gammalinolenate (GLA) has been shown to possess antitumor activity on various human cancer cell lines in vitro and some evidence has been found of its modulative activity on tubulin active agents, such as vinca alkaloids. GLA treatment is thought to change the penetration and distribution of chemotherapeutic agents in pancreatic tumor tissue. The in vivo effects of GLA are widely unknown. This is the first study on the modulation effects of both oral or intravenous GLA on blood perfusion in vivo. We analysed tissue perfusion prior to treatment and on the 10th day of GLA treatment in patients with pancreatic cancer. Dynamic gamma imaging was performed for 20 minutes after Tc-99m-MIBI injection, and the whole body was scanned after the dynamic study and at 4 hours. Half-lives in liver, left kidney, spleen, pancreas and tumor were recorded using a developed macro program for background corrected geometric mean data from irregular region of interests. Half-lives in the liver did not change due to oral GLA treatment, but they decreased dramatically in two of three patients after i.v. GLA treatment. Additionally, individual changes were observed in pancreatic half-lives, as in four out of five cases the half-life increased and in one case it decreased. No major changes were observed in kidney and spleen half-lives. GLA treatment had no effects on the blood brain barrier. This technique demonstrates perfusion in salivary glands, thyroid, lungs, heart, spleen, kidneys, muscles, spine and bladder, but no changes in perfusion could be detected due to GLA treatment. However, qualitatively enhanced blood flow through the pancreatic tumor was observed. In all patients irrespective of the route of administration of GLA, the organ-to-background ratios in liver decreased. The effect is, however, smallest after oral dosing. The pancreas-to-background ratio was increased in 3/5 patients, these patients exhibited stabilized disease. In a patient with large liver metastases the pancreas-to-background ratio decreased, and she showed a rapid disease progression during GLA therapy. The change in the pancreatic uptake was inversely proportional to the change in CA 19-9 concentration. Our results indicate the that GLA treatment dramatically changes tissue perfusion, especially in liver and pancreatic tumors, even at low doses, and these changes may predict response to GLA therapy.

Abdominal SPECT/MRI fusion applied to the study of splenic and hepatic uptake of radiolabeled thrombocytes and colloids.

The importance of applying MRI (CT)/SPECT fusion in the abdominal and thoracic areas has been recognized in recent studies aiming at radionuclide therapy of cancer. According to our earlier results spleen and liver volume determination with different segmentation methods is inaccurate with SPECT alone. We therefore applied a SPECT/MRI registration procedure to the estimation of spleen and liver volumes and spleen/liver activity ratios in three male volunteers administered 111In-labeled thrombocytes and 99mTc-labeled colloids. The objectives of the study were to investigate if the uptake of thrombocytes in the spleen and liver can be measured more accurately when the anatomical borders of these organs are transferred from MRI to SPECT, and to test a SPECT/MRI registration method for improving three-dimensional dosimetry for radiotherapy treatment planning. A good correlation was found between spleen/liver activity ratios calculated from volumetric average activity per pixel values and from total volumetric counts derived from registered data but not from projection data. The average registration residual with this SPECT/MRI fusion method is approximately 1-2 cm in the abdominal area. Combining anatomical images with SPECT is therefore important for improving quantitative SPECT also in the abdomen.

Detection of pseudomyxoma peritonei by radioimmunohistochemistry and radioimmunoscintigraphy.

Pseudomyxoma peritonei (PP) is a local slowly progressing disease with typical abdominal swelling. Treatment is uneffective and the long-term prognosis is poor. Conventional radiology provides usually only a delineation of low density area relating gelatinous masses accumulating in the peritoneal cavity. In this study, immunohistochemistry based on digital quantitative autoradiography utilizing radiolabelled monoclonal antibody B72.3 (MoAb) recognizing TAG-72 antigen on epithelial carcinomas was used for diagnosis of pseudomyxoma (7 patients). The PP patients were studied with radioiodinated I-131-labeled MoAb after intravenous (2 patients) and intraperitoneal (7 patients) injections. Radioactivities of MoAbs varied considerably in the tumors. Both intra- and extracellular staining pattern was observed by immunohistochemistry. Gamma imaging at 1, 3, 7 and 14 days after i.v. injection (2 patients) revealed targeting of all known lesions. The intraperitoneally injected MoAb (7 patients) retained long time in the peritoneal cavity, specific tumour targeting was seen up to 16 days by an antibody-SPECT, while maximum blood radioactivity was measured between 8-12 hrs. Radiolabelled B72.3 MoAb recognizing TAG-72 antigen is also present within pseudomyxoma cells. It can be used for radioimmunohistochemistry of PP. Accurate imaging of PP is possible by MoAb suggesting earlier diagnosis and more accurate location of residual disease after operations, and evaluating treatment response. Estimated tumour dose for intraperitoneal tumour (MIRD formalism) was 13 mGy/MBq. This indicates that the radioiodinated B72.3 antibody can be used for in vivo targeting and therapeutic applications of intraperitoneal pseudomyxoma.

Double-tracer dosimetry of organs in assessment of bone marrow involvement by two monoclonal antibodies.

Five patients with ductal breast cancer were studied using simultaneous administration of 99Tcm-labelled BW250/183 and 131I-labelled B72.3 monoclonal antibodies (MAbs). The distribution and dosimetry of these tracers were evaluated using the information from simultaneous anterior and posterior whole body scintigrams, together with 99Tcm and 131I standard activity sources, recorded on an average of 1, 4, 24, 90 and 224 h after injection. A method to eliminate 131I Scatter on 99Tcm-channel was developed. The geometric means of conjugate views and region-of-interest analysis were used to determine organ uptakes, mean residence times and absorbed radiation dose estimates of organs induced by the tracers. Organ uptakes (% of injected activity/ml) varied from 6.2 x 10(-3 /red marrow to 3.1 X 10(-2)/liver for 99Tcm-MAb and from 3.1 x 10(-2)/red marrow to 1.8 x 10(-1)/liver for 131I-MAb, one hour after injection. Calculated average residence times of organs for 99Tcm-labelled BW250/183 were in the range of physical mean-life of 99Tcm and from 71 to 95 h for 131I-B72.3 respectively. The average total absorbed dose from 99Tcm-MAb to the bone marrow was 0.01 and to the spleen 0.14 mGy/MBq and from 131I-MAb the corresponding values were 0.48 and 10.76 mGy/MBq. This double-tracer technique provides information from two antibodies having different kinetic behaviour and may facilitate in distinguishing various antigens in targeting and control MAb applications.

191Os/191mIr-generator for studying arterial blood flow in experimental animal models.

Iridium-191m (191mIr, t1/2 = 4.96 sec), an ultra-short lived tracer, has turned out to be suitable for gamma imaging. It can be obtained in high yields from an 191Os/191mIr-generator with a low 191Os breakthrough. In this study the blood flow in the carotid and kidney arteries was studied in rabbits by radionuclide arteriograms. In addition, the whole body retention and biodistribution of 191Os was studied in rats. 191mIr was obtained from an activated carbon system, in a modification of the procedure described in the literature. The kidney regions (study I) of rabbits were imaged dynamically (5 frames/second) for up to 40 seconds, and the investigations were repeated 4-7 times in the same animal. Similarly, the carotid arteries were studied (study II) and from the curves flow parameters were calculated. In order to study the 191Os breakthrough two groups of rats (n = 5) were sacrificed one day and four days after injecting five diagnostic doses into the tail vein (study III). In study III the Os-retention was highest in the kidneys and spleen, followed by the muscles and liver: 0.11-0.12% ID/g tissues were obtained at 1 day and 0.10-0.13% ID/g at 4 days, respectively. These values indicate that the breakthrough values are by no means toxic and that investigations can be repeated immediately with a negligible radiation exposure. The investigations performed with the same animals (I-II) could be easily repeated and were reproducible. All of this indicates that 191mIr is suitable for radionuclide angiography and the generator system is simple and safe to use (191Os is beta-emitter).(ABSTRACT TRUNCATED AT 250 WORDS)