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Pinhole collimation is widely recognized for offering superior resolution-sensitivity trade-off in SPECT imaging of small subjects. The newly developed EXIRAD-3D autoradiography technique (MILabs B.V.) based on a highly focusing multi-pinhole collimator achieves micron-resolution SPECT for cryo-cooled tissue samples. For such high resolutions, the choice of pinhole material may have a significant impact on images. Therefore, this paper aims to compare the performance of EXIRAD-3D with lead, tungsten, gold, and depleted uranium pinhole collimators designed such that they achieve equal sensitivities. Performance in terms of resolution is characterized for several radioisotopes, namely 111 In (171 keV and 245 keV), 99m Tc (140 keV), 201 Tl (71 keV), and 125 I (27 keV). Using Monte Carlo simulation, point spread functions were generated and their profiles as well as their full-width-at-half-maximum and full-width-at-tenth-maximum were determined and evaluated for different materials and isotopes. Additionally, simulated reconstructions of a Derenzo resolution phantom, validated with experimental data, were judged by assessment of the resolvable rods as well as a contrast-to-noise ratio (CNR) analysis. Our results indicate that using materials with higher photon-stopping power yields images with better CNR for the studied isotopes with improvements ranging from 1.9% to 36.6%. Visual assessment on the reconstructed images suggests that for EXIRAD-3D, the tungsten collimator is generally a good choice for a wide range of SPECT isotopes. For relatively high-energy isotopes such as 111 In, using gold inserts can be beneficial.

The changes in β-cell mass (BCM) during the development and progression of diabetes could potentially be measured by radionuclide imaging using radiolabeled exendin. In this study, we investigated the potential of 111 In-diethylenetriaminepentaacetic acid-exendin-3 ( 111 In-exendin) in a rat model that closely mimics the development of type 1 diabetes (T1D) in humans: BioBreeding diabetes-prone (BBDP) rats. BBDP rats of 4-18 weeks of age were injected intravenously with 111 In-exendin, and single-photon emission computed tomography (SPECT) images were acquired. The accumulation of the radiotracer was measured as well as the BCM and grade of insulitis by histology. 111 In-exendin accumulated specifically in the islets, resulting in a linear correlation with the BCM (%) (Pearson r = 0.89, P < 0.0001, and r = 0.64 for SPECT). Insulitis did not have an influence on this correlation. These results indicate that 111 In-exendin is a promising tracer to determine the BCM during the development of T1D, irrespective of the degree of insulitis., (© 2018 by the American Diabetes Association.)

Purpose: The purpose of this study was to investigate how intravenously injected bone marrow-derived mesenchymal stem cells (BMSCs) are distributed in the body of an Alzheimer's disease (AD) animal model., Methods: Stem cells were collected from bone marrow of mice and labeled with Indium-111 ( 111 In). The 111 In-labeled BMSCs were infused intravenously into 3×Tg-AD mice in the AD group and non-transgenic mice (B6129SF2/J) as controls. Biodistribution was evaluated with a gamma counter and gamma camera 24 and 48 h after injecting the stem cells., Results: A gamma count of the brain showed a higher distribution of labeled cells in the AD model than in the control group at 24 (p = .0004) and 48 h (p = .0016) after injection of the BMSCs. Similar results were observed by gamma camera imaging (i.e., brain uptake in the AD model was significantly higher than that in the control group). Among the other organs, uptake by the spleen was the highest in both groups. More BMSCs were found in the lungs of the control group than in those of the AD group., Conclusions: These results suggest that more intravenously infused BMSCs reached the brain in the AD model than in the control group, but the numbers of stem cells reaching the brain was very small.

The study's aim was to image severe alcoholic hepatitis (SAH) using 111 In-labelled leucocytes with two objectives in mind: firstly for non-invasive diagnosis and secondly to provide a platform for experimental therapies aiming to inhibit intrahepatic neutrophil migration. 111 In-leucocyte scintigraphy was performed 30 min and 24 h post-injection in 19 patients with SAH, 14 abstinent patients with alcohol-related cirrhosis and 11 normal controls. Eleven with SAH and seven with cirrhosis also had 99m Tc-nanocolloid scintigraphy. Change in hepatic 111 In radioactivity was expressed as decay-corrected 24 h:30 min count ratio and, in SAH, compared with histological grading of steatohepatitis and expression of granulocyte marker, CD15. Hepatic microautoradiography on biopsy specimens obtained 24 h post-injection of 111 In-leucocytes was performed in one patient. Median 24 h:30 min hepatic 111 In activity ratio was higher in SAH (2.5 (interquartile range (IQR): 1.7-4.0) compared with cirrhotics and normal controls (1.0 (0.8-1.1) and 0.8 (0.7-0.9) respectively, P <0.0001). In SAH, it correlated with CD15 expression (r = 0.62, P =0.023) and was higher in marked compared with mild/moderate steatohepatitis (4.0 (3.0-4.6) compared with 1.8 (1.5-2.6), P =0.006). Hepatic-to-splenic 99m Tc count rate ratio was reduced in SAH (0.5 (0.4-1.4)) compared with cirrhotics (2.3( 0.6-3.0)) and three historic normal controls (4.2 (3.8-5.0); P =0.003), consistent with impaired hepatic reticuloendothelial function. Scintigraphic findings in SAH included prominent lung radioactivity at 30 min, likely the result of neutrophil primimg. Microautoradiography demonstrated cell-associated 111 In in areas of parenchymal neutrophil infiltration. In conclusion, 111 In-leucocyte scintigraphy can non-invasively diagnose SAH and could provide a platform for evaluation of novel treatments aiming to inhibit intrahepatic neutrophil migration., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

A novel pretargeted SPECT imaging strategy based on the HaloTag enzyme has been evaluated for the first time in a living system. To determine the efficacy of this approach, two clinically relevant cancer biomarkers, HER2 and TAG-72, were selected to represent models of internalizing and noninternalizing antigens, respectively. In MDA-MB-231/H2N (HER2-expressing) and LS174T (TAG-72-expressing) xenograft tumors in mice, pretargeting experiments were performed in which HaloTag-conjugated derivatives of the antibodies trastuzumab (anti-HER2) or CC49 (anti-TAG-72) were utilized as primary agents, and the small molecule HaloTag ligands 111 In-HTL-1, -2, and -3 were evaluated as secondary agents. While this approach was not sufficiently sensitive to detect the internalizing HER2 antigen, pretargeting experiments involving the most optimal secondary agent, 111 In-HTL-3, were successful in detecting the noninternalizing antigen TAG-72 and provided high-contrast SPECT images at 4 and 24 h postinjection.

Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in β-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total β-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate β-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of β-cells. Uptake of a promising radiotracer for β-cell imaging by SPECT, (111)In-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of (111)In-exendin-3 and insulin positive β-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of β-cell radiotracers.

The International Commission on Radiological Protection (ICRP) Task Group that developed the Human Respiratory Tract Model for Radiological Protection (HRTM) identified a lack of published information on aspects of the clearance of inhaled particles deposited in the human nasal passage. Using the results of a recent human volunteer study on the clearance of inhaled particles from the nose, a revised model of clearance from the extra-thoracic (ET) airways has been developed that addresses important issues for which simplifying assumptions had to be made in the ICRP Publication 66 HRTM ET model. This ET clearance model has been adopted by ICRP for inclusion in the revised HRTM. The derivation of the model and parameter values from the experimental data are explained.

Introduction: Since Pall-German stopped manufacturing ITLC-SG, it has become necessary to validate alternative stationary phases., Objective: To validate different stationary phases versus ITLC-SG Pall-Gelman in the determination of the radiochemical purity (RCP) of (111)In-pentetreotide ((111)In-Octreoscan) by planar chromatography., Material and Methods: We conducted a case-control study, which included 66 (111)In-pentetreotide preparations. We determined the RCP by planar chromatography, using a freshly prepared solution of 0,1M sodium citrate (pH 5) and the following stationary phases: ITLC-SG (Pall-Gelman) (reference method), iTLC-SG (Varian), HPTLC silica gel 60 (Merck), Whatman 1, Whatman 3MM and Whatman 17. For each of the methods, we calculated: PRQ, relative front values (RF) of the radiopharmaceutical and free (111)In, chromatographic development time, resolution between peaks. We compared the results obtained with the reference method. The statistical analysis was performed using the SPSS program. The p value was calculated for the study of statistical significance., Results: The highest resolution is obtained with HPTLC silica gel 60 (Merck). However, the chromatographic development time is too long (mean=33.62minutes). Greater resolution is obtained with iTLC-SG (Varian) than with the reference method, with lower chromatographic development time (mean=3.61minutes). Very low resolutions are obtained with Whatman paper, essentially with Whatman 1 and 3MM. Therefore, we do not recommend their use., Conclusions: Although iTLC-SG (Varian) and HPTLC silica gel 60 (Merck) are suitable alternatives to ITLC-SG (Pall-Gelman) in determining the RCP of (111)In-pentetreotide, iTLC-SG (Varian) is the method of choice due to its lower chromatographic development time., (Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.)

Polymersomes, self-assembled from the block copolymer polybutadiene-block-poly(ethylene glycol), were prepared with well-defined diameters between 90 and 250 nm. The presence of ~1% of diethylene triamine penta acetic acid on the polymersome periphery allowed to chelate radioactive (111)In onto the surface and determine the biodistribution in mice as a function of both the polymersome size and poly(ethylene glycol) corona thickness (i.e., PEG molecular weight). Doubling the PEG molecular weight from 1 kg/mol to 2 kg/mol did not change the blood circulation half-life significantly. However, the size of the different polymersome samples did have a drastic effect on the blood circulation times. It was found that polymersomes of 120 nm and larger become mostly cleared from the blood within 4 h, presumably due to recognition by the reticuloendothelial system. In contrast, smaller polymersomes of around 90 nm circulated much longer. After 24 h more than 30% of the injected dose was still present in the blood pool. This sharp transition in blood circulation kinetics due to size is much more abrupt than observed for liposomes and was additionally visualized by SPECT/CT imaging. These findings should be considered in the formulation and design of polymersomes for biomedical applications. Size, much more than for liposomes, will influence the pharmacokinetics, and therefore, long circulating preparations should be well below 100 nm.

Continuous environmental or occupational exposure to airborne particulate pollution is believed to be a major hazard for human health. A technique to characterize their deposition and clearance from the lungs is fundamental to understand the underlying mechanisms behind their negative health effects. In this work, we describe a method for production and follow up of ultrafine carbon particles labeled with radioactive ¹¹¹Indium (¹¹¹In). The physicochemical and biological properties of the aerosol are described in terms of particle size and concentration, agglomeration rate, chemical bonding stability, and human lung deposition and retention. Preliminary in vivo data from a healthy human pilot exposure and 1-week follow up of the aerosol is presented. More than 98% of the generated aerosol was labeled with Indium and with particle sizes log normally distributed around 79  nm count median diameter. The aerosol showed good generation reproducibility and chemical stability, about 5% leaching 7 days after generation. During human inhalation, the particles were deposited in the alveolar space, with no central airways involvement. Seven days after exposure, the cumulative activity retention was 95.3%. Activity leaching tests from blood and urine samples confirmed that the observed clearance was explained by unbound activity, suggesting that there was no significant elimination of ultrafine particles. Compared to previously presented methods based on Technegas, ¹¹¹In-labelled ultrafine carbon particles allow for extended follow-up assessments of particulate pollution retention in healthy and diseased lungs.

The measurement of recovery and survival of platelets is an important decisive factor when 'new' platelet products have been developed. Recovery and survival measurements are mostly performed with radioactive-labeled platelets in healthy volunteers. This approach is required by the FDA for acceptance of platelet products that differ substantially in production or storage conditions from standard methods. However, due to regulatory obstacles, such radiolabeling studies are only carried out in designated institutes. Many countries do not require radioactive labeling studies in volunteers prior to accepting new products, and rather rely on surrogate tests. Also, the European guide to the preparation of blood components does not require this step. This paper reviews alternative, non-radioactive methods, which includes biotinylation of platelets, and discrimination of transfused platelets based on HLA discrepancy. The benefits and disadvantages of these methods will be discussed., ((c) 2009 Elsevier Ltd. All rights reserved.)

A new strategy for the radiolabeling of porous nanocontainers has been developed, and the first experiments in vivo are reported. Our approach consists of the use of nanometer-sized zeolites whose channels have been filled with the positively charged gamma-emitter (111)In(3+) via simple ion exchange. To avoid leaching of the isotope under physiological conditions, the entrances of the channels have been closed using a specifically designed molecular stopcock. This stopcock has a positively charged group that enters the channels and entraps the loaded radionuclides via electrostatic and steric repulsion. The other side of the stopcock is a bulky triethoxysilane group that can covalently bind to the walls of the zeolite entrances, thereby irreversibly closing the channels. The surface of the zeolites has been functionalized with different chemical groups in order to investigate the different biodistributions depending of the nature of the functionalizations. Preliminary in vivo experiments with Wistar rats have been performed and showed the potential of the approach. This strategy leads to a nanoimaging probe with a very high density of radioisotopes in a confined space, which is highly stable in physiological solution and could allow a large variety of functionalities on its external surface.

Objective: Yttrium-90 (Y)-labelled peptides such as DOTATOC and antibodies such as Zevalin are widely used in radionuclide therapy. Indium-111 (In) is used as a Y surrogate for imaging and dosimetry purposes. We aimed to investigate accuracy, geometry (vials and syringes) and volume dependencies for both radionuclides in several different radionuclide calibrators., Methods: YCl3 and InCl3 solutions were gravimetrically dispensed into the most frequently used containers. In each container several dilutions of the parent solutions were performed. Mass, activity and time were recorded for each calibrator and measurement. Aliquots of both parent solutions were calibrated at the National Metrology Laboratory, Vienna, Austria (BEV). From our measurements and results from BEV, correction factors were determined and further partitioned into calibration, geometry and volume correction factors., Results: Using the nominal calibration factors provided by the manufacturer, measured activity in P6 vials was overestimated by up to 25% for In, depending on the calibrator. Y activity was either underestimated (by up to 20%) or overestimated (by up to 25%) using different radionuclide calibrators. This is the result of the difference in containers used to set the manufacturer's calibration factor values and the containers used in nuclear medicine departments and in this study. There was little geometry dependence for glass vials but strong geometry dependence for syringes for both radionuclides in all calibrators., Conclusion: The results should constitute a warning for all personnel responsible for preparation of radiopharmaceuticals. Every nuclear medicine department should incorporate a proper quality-control regimen for radionuclide calibrators and a quality-assurance system.

Unlabelled: Absorbed-dose calculations provide a scientific basis for evaluating the biologic effects associated with administered radiopharmaceuticals. In cancer therapy, radiation dosimetry supports treatment planning, dose-response analyses, predictions of therapy effectiveness, and completeness of patient medical records. In this study, we evaluated the organ radiation absorbed doses from intravenously administered (111)In- and (90)Y-ibritumomab tiuxetan., Methods: Ten patients (6 men and 4 women) with non-Hodgkin lymphoma, cared for at 3 different medical centers, were administered the tracer (111)In-ibritumomab tiuxetan and assessed using planar scintillation camera imaging at 5 time points and CT-organ volumetrics to determine patient-specific organ biokinetics and dosimetry. Explicit attenuation correction based on the transmission scan or transmission measurements provided the fraction of (111)In-administered activity in 7 major organs, the whole body, and remainder tissues over time through complete decay. Time-activity curves were constructed, and radiation doses were calculated using MIRD methods and implementing software., Results: Mean radiation absorbed doses for (111)In- and for (90)Y-ibritumomab tiuxetan administered to 10 cancer patients are reported for 24 organs and the whole body. Biologic uptake and retention data are given for 7 major source organs, remainder tissues, and the whole body. Median absorbed dose values calculated by this method were compared with previously published dosimetry for ibritumomab tiuxetan and the product package insert., Conclusion: In high-dose radioimmunotherapy, the importance of patient-specific dosimetry becomes obvious when the objective of treatment planning is to achieve disease cures, safely, by limiting radiation dose to any critical normal organ to its maximum tolerable value. Compared with the current package insert, we found differences in median absorbed dose by multiples of 24 in the kidneys, 1.8 in the red marrow, 0.65 in the liver, 0.077 in the intestinal wall, 0.30 in the lungs, 0.46 in the spleen, and 0.34 in the heart wall.

The Swedish regulations concerning disposal of clinical radioactive waste are currently under revision and a graded approach is proposed for risk limitation purposes. To assist the revision procedures, a screening study was performed to estimate public exposures from liquid releases from hospitals to public sewers. The results showed that doses to sewage workers were above the dose constraint of 100 microSv a(-1) especially for 131I and (99m)Tc. Hence, a dynamic model, LUCIA, was developed for realistic assessments in which radionuclide transportation in sewers was modelled. Probabilistic simulations were performed to obtain probability distributions of radionuclide concentrations in sludge. Concurrently, estimates of the effective doses to sewage workers decreased significantly and were below 10 microSv a(-1) except for 111In and 131I. However, the Kd-coefficients representing the partition of radioactivity between water and sludge in sewers are highly uncertain for 111In. As shown by sensitivity studies, these values are the major determinant of the exposures in sewers.

Monte Carlo simulations are useful for optimizing and assessing single photon emission computed tomography (SPECT) protocols, especially when aiming at measuring quantitative parameters from SPECT images. Before Monte Carlo simulated data can be trusted, the simulation model must be validated. The purpose of this work was to validate the use of GATE, a new Monte Carlo simulation platform based on GEANT4, for modelling indium-111 SPECT data, the quantification of which is of foremost importance for dosimetric studies. To that end, acquisitions of (111)In line sources in air and in water and of a cylindrical phantom were performed, together with the corresponding simulations. The simulation model included Monte Carlo modelling of the camera collimator and of a back-compartment accounting for photomultiplier tubes and associated electronics. Energy spectra, spatial resolution, sensitivity values, images and count profiles obtained for experimental and simulated data were compared. An excellent agreement was found between experimental and simulated energy spectra. For source-to-collimator distances varying from 0 to 20 cm, simulated and experimental spatial resolution differed by less than 2% in air, while the simulated sensitivity values were within 4% of the experimental values. The simulation of the cylindrical phantom closely reproduced the experimental data. These results suggest that GATE enables accurate simulation of (111)In SPECT acquisitions.

Unlabelled: Our goal was to design and manufacture a kit under good manufacturing practices (GMP) for the preparation of (111)In-DTPA-hEGF Injection, a novel targeted radiotherapeutic agent for advanced epidermal growth factor receptor (EGFR)-positive breast cancer., Methods: Human EGF (hEGF) was derivatized with diethylenetriaminepentaacetic acid (DTPA) and then purified by size-exclusion chromatography and ultrafiltration. Kits were prepared by dispensing 0.25 mg (1 mL) of DTPA-hEGF in 1 mol/L sodium acetate buffer [pH 6.0] into single-dose glass vials. Raw materials were pharmacopoieal or reagent grade according to the American Chemical Society and were tested for identity and purity. Kits were tested for protein concentration, purity and homogeneity (sodium dodecyl sulfate polyacrylamide gel electrophoresis and size-exclusion high-performance liquid chromatography), pH, clarity and color, volume, DTPA substitution, labeling efficiency, receptor binding to MDA-MB-468 human breast cancer cells, and sterility and apyrogenicity. (111)In-DTPA-hEGF Injection was tested for pH, radionuclidic and radiochemical purity, clarity and color, and sterility and apyrogenicity., Results: Four lots of kits and 8 lots of (111)In-DTPA-hEGF Injection passed all quality specifications. The labeling efficiency was 94%-99% with 115-773 MBq (111)In chloride added to a single kit. (111)In-DTPA-hEGF exhibited preserved receptor binding against MDA-MB-468 cells (affinity constant [K(a)], 0.9-1.1 x 10(7) L/mol; maximum number of binding sites per cell [B(max)], 1.1-2.2 x 10(6) sites per cell). In addition, labeling of aliquots of the kit suggested that a single vial could be labeled with up to 3,083 MBq (111)In while maintaining a radiochemical purity of >90%. Kits were stable for >90 d and (111)In-DTPA-hEGF Injection was stable for >24 h stored at 4 degrees C., Conclusion: The kit formulation is suitable for preparing (111)In-DTPA-hEGF Injection for a phase I clinical trial in patients with advanced EGFR-positive breast cancer. Establishment of the GMP processes for (111)In-DTPA-hEGF Injection provides a useful example of manufacturing biotechnology-based investigational radiopharmaceuticals in an academic environment for early phase I clinical trials.

A new method using the Monte Carlo code PENELOPE for ionization chamber simulation has already been successfully used for calculating calibration factors needed for the measurements of radionuclides with photon emission (2003, Appl. Radiat. Isot., to be published). This work has been continued at (Laboratoire National Henri Becquerel) in order to calculate the calibration factors for radionuclides with short half-lives used in medical services. Activity measurements of 18F, 99mTc,111In and 123I using the calculated calibration factors were obtained with standard uncertainties equal to 0.6% for 18F, 99mTc and 1.5% for 111In and 123I.

Background: Few studies have examined tumor cell distribution following laparoscopic surgery for colorectal cancer. We examined the effect of carbon dioxide pneumoperitoneum on the distribution of intrasplenically injected colon cancer cells in mice., Methods: Mice were intrasplenically injected with 2 x 10(4) colon 26 cells labeled with 111In-oxine and were randomized to undergo pneumoperitoneum at 10 mmHg for 30 min or to receive no treatment other than anesthesia. Radioactivity of the liver, lungs, and spleen was measured 30, 60, 90, or 150 min following tumor inoculation., Results: The dynamic changes in the hepatic radioactivity were not similar between groups. However, the values were not significantly different at any time point. The radioactivity of lungs was extremely low in both groups throughout the experimental period., Conclusions: Pneumoperitoneum does not appear to cause the accumulation of intraportally spreading tumor cells in the liver, but it may affect the dynamic changes of tumor cells. Also, tumor cell localization in the lungs is negligible in both pneumoperitoneum and control groups.

Unlabelled: A new type of well-scintillation counter with a double-well and single-plastic scintillator (DW-counter) was developed to simplify time consuming and cumbersome dilution procedures inherent to in-vivo sample measurement. It has the potential to measure many radionuclides which emit a gamma ray or positron. We tested the counting efficiency (CE) of the DW-counter (DCM-200, Aloka Co., Tokyo, Japan) with respect to 6 radionuclides., Materials and Methods: The outline of DW-counter is altered to a single unit as compared to the prototype, while its basic mechanical constitution was not changed. Six commercially available radionuclides (Tl-201, Tc-99m, I-123, Ga-67, In-111, I-131) were used in this study. For each radionuclide, we prepared two standard solutions containing high (>100 MBq/ml) and relatively low radioactivity (10-20 MBq/ml). The radioactivity (Bq) of the radionuclide in each sample at time = 0 was measured with a dose calibrator. Afterwards, it was determined from a decay-time with correction by the physical half-life of each radionuclide. Count rate (cps) of each standard sample was measured in each well ten times per sample. The counting efficiency (CE) of the counter for each radionuclide was determined by measured count rate (cps)/standard radioactivity (Bq) x 100 (%). The conversion constant (CC) which predicts standard radioactivity (Bq) from measured count rate (cps) was obtained as a reciprocal value of the CE., Results: The CE (mean +/- SD) in well-A to Tl-201, Tc-99m, I-123, Ga-67, In-111 and I-131 was 5.90 +/- 0.285%, 8.56 +/- 0.0981%, 8.33 +/- 0.344%, 7.77 +/- 0.15%, 16.4 +/- 0.495% and 10.2 +/- 0.139%, respectively. They were significantly different. The coefficient of variation of the measured count rates was less than 1% in radioactive range higher than 10(3) Bq in well-A and 106 Bq in well-B. The difference in the CE between well-A and -B ranged from 7.614 x 10(2) (I-131) to 9.395 x 10(2) (Tl). The CC ranged from 6.14 (In) to 17.15 (Tl) in well-A and from 5.05057 x 10(3) (In) to 15.83773 x 10(3) (Tl) in well-B. The CE was not significantly affected by a sample volume from 1 to 4 ml in well-A, but showed a slight difference in well-B, which seemed due to a collimation., Conclusion: The measurement error of the DW-counter was less than 1% and the measured count rate (cps) was exactly converted to the standard radioactivity (Bq) by determined CC. The counter is considered useful in the easy evaluation of in-vivo tracer kinetics by avoiding time consuming and cumbersome dilution techniques.

Background: Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular function after experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs., Methods and Results: Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [111In]indium oxine. EPCs (106) were injected in athymic nude rats 24 hours after myocardial infarction (n=8) or sham operation (n=8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, approximately 70% of the radioactivity was localized in the spleen and liver, with only approximately 1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02+/-0.19 in sham-operated animals to 2.03+/-0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69+/-1.54 in sham-operated animals to 4.70+/-1.55 (P<0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone., Conclusions: Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy.

Previously, during blood perfusion over collagen-coated surfaces; soluble or immobilized heparin proteoglycans (HEP-PG) have been shown to block thrombus growth. Our aim was to study the antithrombotic effect of locally applied unfractionated heparin (UFH, 1 mg/ml), or rat mast cell-derived HEP-PG (MW 750 kD, 10 microg/ml) compared with saline in early (10 min) and late (3 days) thrombus formation upon anastomosis of rat common femoral arteries. In both semiquantitative scanning electron microscopy (SEM) and quantitative platelet Indium 111-labeling HEP-PG inhibited thrombus growth in comparison with saline. At 10 min, the extent of thrombosis (scale 1-4) in SEM followed the order: saline (3.2+/-0.8) > UFH (2.8+/-1.0) > HEP-PG (1.8+/-0.8), and also Indium 111-positive platelets (10(6)) accumulated on the anastomosed vessel in the same order 14.2 +/-7.2, 10.3 +/-5.0, and 7.7 +/-3.1 (saline vs. HEP-PG, p = 0.03 and 0.05, respectively). At 3 days all HEP-PG-treated vessels remained patent with only small mural thrombi, whereas 2/7 saline- and 1/7 UFH-treated anastomoses occluded and showed more thrombosis overall. We conclude that locally administered HEP-PG inhibit arterial thrombus growth in anastomosed small-sized arteries and could prevent thrombotic complications in (micro)vascular surgery and arteriovenous shunts.

Variation in the amounts of radioactivity that is associated with dose calibration and administration of gamma-emitting radioactive drugs was studied. Health systems use radionuclide dose calibrators when they need to assay drugs for radioactivity. However, the radioactive drugs commonly used for therapeutic or diagnostic purposes are compounded and assayed in or administered from containers that differ from those containing the standard reference materials (SRMs). SRMs for four radionuclides--technetium 99m, indium 111, thallium 201, and iodine 131--were drawn up into vials and syringe-needle assemblies of volumes and sizes represented in clinical practice. In each sample, the amount of radioactivity was calculated and compared with values obtained from three dose calibrators. In addition, over a four-month period, 101 samples of technetium Tc 99m medronate injection with a desired activity of 20 mCi were prepared in syringes; the radioactive dose in each syringe was calibrated for administration to a patient at a specific time that day. The amounts of radioactivity at the time of preparation and the time of administration, the amount remaining in the syringe and needle after administration, and the amount reported as administered were recorded. Measurement with the dose calibrators of the SRMs in containers supplied by the National Institute of Standards and Technology showed radioactivity within 10% of the labeled amount, the percentage of variation regulations allow. Measurements of the SRMs in syringe-needle assemblies were within 10% for technetium 99m and thallium 201, 9-16% for iodine 131, and 15-26% for indium 111. The individual doses of technetium 99m medronate injection were, on average, administered on time, but doses were administered up to 75 minutes before and 107 minutes after the calibration time. The mean +/- S.D. amount administered was 19.0 +/- 1.34 mCi. The mean +/- S.D. amount reported administered was 20 +/- 0.24 mCi. How radiopharmaceuticals were dose calibrated and administered influenced the actual dose available to patients.

Determination of the biodistribution of radiopharmaceuticals is an important issue for the evaluation of their performance in diagnosis and therapy. In this study, we evaluated a digital radioimager (RI) based on a multiwire proportional chamber for quantitative autoradiography (AR). The RI allows direct detection of electronic emissions of gamma emitters. Its qualitative and quantitative performances were tested on 99mTc and (111)In labelled sections and compared with conventional film AR. Linearity of count rate versus activity was verified over a 104 range of activity. As compared with film AR, a substantial improvement of the detection limit was obtained even for acquisition periods up to 20 times less than film exposure times. We provided the basis for quantitative analysis with tissue equivalent paste standards: the 99mTc and (111)In RI counting efficiencies were respectively 1.19% and 2.35%. We illustrated the respective values of RI and film AR in two rat studies: 99mTc-DMSA in kidney and dual-isotope 99mTc-MIBI and (111)In-antimyosin in heart. Calculated activity concentrations on sections of rat organs confirmed good correlation to gamma counting (deviation less than 12%). We suggest RI as a convenient technique for fast localization of single or dual-isotope tracers and determination of activity distribution.

Objective: The accurate measurement of radionuclides in a dose calibrator can be affected by container geometry especially for low-energy photons. This study investigated the effectiveness of using copper filtration for selective absorption of low-energy x-rays during the measurement of 123I and 111In to minimize variations in measurement as a function of geometry., Methods: Copper absorbers of varying thickness were used to define the absorption profile of low-energy x-rays in the 20- to 50-keV energy window with 125I and a gamma scintillation spectrometer. Iodine-123 and 111In standards were assayed in a dose calibrator, with and without a copper filter positioned in the ion chamber well, to determine new isotope calibration settings for these nuclides with the copper filter. Samples of 123I and 111In, of constant activity but various volumes, were assayed in 1-ml, 3-ml and 10-ml plastic syringes and a 10-ml glass vial with and without copper filtration to assess the influence of geometry on the accuracy of measurement., Results: A copper thickness of 0.6 mm removed 99.5% of 125I photons in the 20- to 50-keV window and significantly reduced the low-energy component of 123I and 111In. Activity measurements of 123I and 111In in the dose calibrator varied with container type and volume without copper filtration but were essentially unchanged when a copper filter was used., Conclusion: A copper filter > or = 0.6 mm thick eliminates the need for geometry correction factors for measuring 123I and 111In with the dose calibrator.

111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).

Since lymphocytes continue to proliferate and divide in vivo, it is important to determine the fate of a radionulide following lymphocyte labelling. Using the mixed lymphocyte reaction (MLR), we induced indium-111 labelled lymphocytes from a specific in-bred rat strain (AS) to divide and then observed the subsequent 111In distribution between cells and supernatant. L10 and L12.4 cells, which are allospecific CD4+ T lymphocytes from the AS rat, were stimulated in the MLR by antigen-presenting cells from the August rat, a different strain. We labelled L10 or L12.4 lymphocytes on day 0, the first day of the stimulation cycle, and continued to culture the lymphocytes in vitro. The proliferation of the cells was estimated according to their increase in number. The distribution of 111In between cell and supernatant fractions and between viable and dead (but intact) cells was measured in the cell suspension each day after labelling. The metabolic activity of 111In-labelled lymphocytes was compared with control cells by measuring their uptake of fluorine-18 fluorodeoxyglucose ([18F]FDG). 111In-labelled lymphocytes showed a poor proliferative response compared with control cells 24-48 h after labelling but increased in number after this time. From 24 to 72 h, about 70% of 111In was in the supernatant but only about 5%-10% was associated with intact dead cells. These dead cells tended to retain their 111In, losing less than 30% per day, suggesting that 111In in the supernatant was the result of active elimination from viable cells. Moreover, 24 h after culture, considerably more 111In was associated with viable than with dead lymphocytes, although over the next few days this distribution reversed. 111In-labelled lymphocytes took up more [18F]FDG than control cells at 24 h but not at 0 or 72-96 h; the maximum [18F]FDG uptake coincided with the greatest reduction in cell number. Furthermore, [18F]FDG uptake correlated with the initial 111In burden in lymphocytes labelled with 111In 24 h previously. The results are consistent with active elimination of 111In by 111In-labelled lymphocytes. The energy requirements for this are diverted away from cell division, thereby increasing the probability of cell death. As lymphocytes become 111In deplete, they recover their capacity to proliferate and their risk of death decreases. These findings have important implications for 111In-labelled lymphocyte scintigraphy, suggesting that cells remaining viable immediately after labelling will either subsequently die or alternatively eliminate the label.

Large hospitals and biomedical research centers utilize decay-in-storage programs to minimize the volume of their low level radioactive waste. However, some medically useful radionuclides often contain small amounts of long-lived radionuclidic impurities which may complicate simple waste management procedures. We have evaluated the extent of this problem in low level radioactive waste involving 67Cu and (111)In over a 6-mo cycle of decay-in-storage by identifying the residual radionuclides in our dry waste using a multichannel analyzer. The multichannel analyzer was also used to quantify the radionuclide constituents of our liquid waste at the beginning of a decay-in-storage cycle. Radionuclides were identified by the presence of characteristic photopeaks of each isotope in the gamma spectrum and quantified by region of interest analysis. After a decay-in-storage cycle, long-lived 58Co, 57Co, and 56Co isotopes were observed in dry 67Cu waste and (114m)In identified in dry (111)In waste. The (114m)In was detected in dry (111)In waste containing initial (114m)In activity of 740 kBq (20 microCi), while the cobalt radionuclides were detected in dry 67Cu waste containing initial 58Co, 57Co, and 56Co activities of 444, 148, and 148 kBq (12, 4, and 4 microCi), respectively. Such dry low level radioactive waste was thus disqualified from short-term radioactive waste storage programs. The radionuclide constituents in the liquid waste were quantified in microCi mL(-1) and confirmed to be within the Nuclear Regulatory Commission set limits of 2 x 10(-4), 6 x 10(-4) and 6 x 10(-5) microCi mL(-1) for 58Co, 57Co, and 56Co, respectively, before disposal. The highest levels of long-lived isotopes that have been found in our liquid low level radioactive waste at the beginning of decay-in-storage were 5.5 x 10(-4), 4.8 x 10(-4), and 1.4 x 10(-4) microCi mL(-1) for 58Co, 57Co, and 56Co, respectively. Gamma spectrometry can be used to aid waste segregation and final management decisions on low level radioactive waste.

This paper reports on a quantitative scintigraphic method for 111In sources using counts from isoboundary regions of interest of source images. Accordingly, total counts from regions of the image excluding the counts below a given percentage of the maximum are recorded and attenuation correction is implemented using the Depth Independent Buildup Factor method which corrects the effects of Compton scattering on the transmission function of the photon flux leaving the source. The transmission function of both the 172 and the 247 keV photons of 111In was determined for a set of circular flat sources of varying diameter (33 to 111 mm), using counts recorded in isoboundary regions of interest of images of the sources placed in air and at various depths in water. The images were acquired using a gamma camera equipped with a parallel hole medium energy collimator. The influence of the isoboundary value on the shape of the transmission function was investigated, and thus the chosen isoboundary value was set to no more than 20% of the maximum count on the image. Two parallel and dimetrically opposed views were acquired to determine the unknown activity of the sources placed in a water phantom. This counting geometry was chosen to operate in conditions of depth independent of the source in the phantom. Our results show a high degree of accuracy, the experimental estimate of the activity obtained by using the counts in the regions of interest with the lowest isoboundary value exhibiting 4% error rate. The error rate increases with the increase in the isoboundary values. The method proved to be simple, practical and accurate. Moreover, it overcomes the problem of accurate estimation of sources size, a variable usually not known with sufficient accuracy in clinical scintigraphic studies.

A computer-based technique for the quantification of abnormal bowel uptake in Crohn's disease has been developed and compared with pre-existing clinical, laboratory and scintigraphic methods of assessment. The standard technique for labelling leucocytes with 99mTc-HMPAO is applied. Images were obtained at 40, 120 and 240 min after the injection of radiolabelled leucocytes. The count in the bowel area after subtracting background activity corrected to the injected dose and image acquisition times is the 'scan score', an objective measure of disease activity. The scan score is significantly higher in patients with clinically active disease (mean 82.1 +/- SEM 13.6) than in those with quiescent disease (24.7 +/- 7.0) (p < or = 0.005). Optimum separation between active and quiescent disease is achieved with a threshold scan score of 20. The scan score was comparable in small bowel disease (73.3 +/- 16.2), large bowel (94.4 +/- 33) and disease at both locations (94.1 +/- 19.2). The scan score correlated favourably with Crohn's Disease Activity Index (rs = 52, p < or = 0.0001), Harvey & Bradshow Simple Index (rs = 0.4, p < or = 0.001), serum C-reactive protein (rs = 0.72, p < or = 0.001), serum alpha acid glycoprotein (rs 0.67, p < or = 0.001), haemoglobin (rs = 0.66, p < or = 0.001), platelet count (rs = 0.47, p < or = 0.006), albumin (rs = 0.61, p < or = 0.0001) and faecal 111Indium excretion (rs = 0.78, p < or = 0.001), but not with the ESR (rs = 0.22, p < or = 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

To clarify the relationship between clotting and lytic activities of intracardiac thrombi, and to elucidate whether this could be used to evaluate the embolic risk the ratio of indium-111 radioactivity accumulated on thrombi to that in the blood pool using dual-tracer technique %IE as a parameter of the clotting activity, and D-dimer, which is a fibrin specific degradation product, as a parameter of lytic activity were measured in 37 patients with intracardiac thrombi. Fifteen of the 37 patients had past histories of arterial embolization. The values of D-dimer correlated significantly with those of %IE (r = 0.758, p less than 0.01), e.g., the higher the values of D-dimer the higher the values of %IE. 37 patients were divided into 2 groups using the regression line for the D-dimer and %IE domains. Eleven patients above the regression line had thrombosis in excess of fibrinolysis but the remaining 26 patients under the regression line had fibrinolysis in excess of thrombosis. The incidence of past embolic episodes was 82% (9/11) in patients with thrombosis in excess of fibrinolysis but 23% (6/26) in patients with fibrinolysis in excess of thrombosis. These results demonstrated that intracardiac thrombi were under the dynamic process between the clotting and the lytic activities and moreover patients with intracardiac thrombi and thrombosis in excess of fibrinolysis had a substantial risk of arterial embolization.

Six patients with reactive arthritis (ReA) were examined for gastrointestinal accumulation of Indium-111 labelled granulocytes. Abnormal scintigrams were found in three of six patients all of which showed early (less than 4 h) accumulation of indium-111 labelled granulocytes which may represent small intestinal inflammation. Our findings may indicate that the small intestine is involved in ReA, and that indium-111 granulocyte scintigraphy is a useful method for demonstrating inflammatory changes in the small intestine in reactive arthritis (ReA).

Anti-human serum albumin antibody (Ab) was used as a model antibody. Ab was conjugated with DTPA using cyclic DTPA dianhydride reaction and radiolabeled with 111In. The labeled Ab was purified by affinity chromatography. Size exclusion HPLC of this product showed 62% of 111In bound to monomeric Ab and 38% of the activity bound to antibody oligomers with molecular weights ranging from 300,000 to 450,000. The labeled antibody preparation was injected into the tail vein of rats. The radioactive substances in serum and the supernatant from liver homogenates were analyzed for molecular weight and immunoreactivity. Size exclusion HPLC of the serum samples indicated that the monomeric and dimeric Abs disappeared from the serum at a similar rate over a 48 h period. In addition, a new radioactive substance with an estimated molecular weight of 35,000 appeared in the serum. The immunoreactive fraction of the circulating 111In substances decreased slowly, somewhat proportional to the appearance of the metabolite. On the other hand, the immunoreactivity of the 111In substances in the supernatant from the liver homogenate decreased rapidly and no appreciable immunoreactivity was observed after 48 h. The labeled antibody was catabolized very rapidly in the liver and the major activity in the supernatant was associated with a small molecular weight metabolite which had a HPLC retention time identical to that of DTPA-111In. The second metabolite had an estimated molecular weight of 35,000. No radioactivity was associated with transferrin.

Conjugates formed by reaction of monoclonal antibody B72.3 with benzyl isothiocyanate derivatives of four amino polycarboxylate chelators (NTA, EGTA, EDTA, DTPA) were labeled with indium-111 and administered iv to athymic mice bearing antigen-positive (LS174T) and antigen-negative (A375) human tumor xenografts. Conjugate immunoreactivities, antibody dose, and xenograft size were controlled, so that the effects of varying chelate structure could be evaluated under conditions where immunological and physiological factors were effectively held constant. Tissue distribution and excretion of the radiometal at 24 and 48 h postinjection were shown to correlate directly with chelate thermodynamic stability (NTA less than EGTA less than EDTA less than DPTA). Radioactivity levels in the blood and the LS174T xenograft increased, while kidney levels and excretion levels decreased, with increasing chelate stability. The kidney was the only normal organ that accumulated non-antibody-bound 111In, uptake of radioactivity into all other tissues, and in particular the liver, being unaffected by changes in chelate structure. Mean transferrin saturation in the tumor-bearing athymic mice was found to be 65%. It is proposed that uptake of free 111In by serum transferrin is precluded in this model, leading to the observed renal localization of unbound label. Kidney:blood and kidney:LS174T activity ratios at 48 h postinjection provided the most sensitive indices of conjugate instability in vivo, spanning 50- and 20-fold ranges, respectively, between the least stable and the most stable conjugate. It is concluded that this antigen/antibody system and mouse model are well-suited to structure-function studies of immunoglobulin labels.

A total of twelve patients with gastroenteropathy were studied for possible protein loss. The underlying diseases were intestinal lymphangiectasia, ulcerative colitis and Crohn's disease in 2 patients each; and Ménétrier's disease, Cronkhite-Canada syndrome, postgastrectomy syndrome, severe atrophic gastritis, gastric cancer and gastroenteropathy of unknown origin in 1 patient each. The controls used in this study were four healthy volunteer and 9 patients with benign disease not accompanied by lesions in the digestive tract and protein loss, 111In-transferrin (Tf) was prepared by incubating 2-3 mCi of 111In-chloride with 15-20 ml of each patient's plasma in a sterilized vial at room temperature for 1 hour. After i.v. injection of 111In-Tf, the patients were scanned at given intervals of time for 72 hours to localize protein loss. 72-hour fecal 111In-Tf excretion was also measured. The following results were obtained: (1) 111In-Tf was detected in the feces of all patients. The recovery rate in the patient group was 7.95 +/- 3.65%, which was significantly higher than 0.48 +/- 0.26% in the control group (p less than 0.01). (2) However, 111In-Tf scanning showed the site of protein loss only in 6 patients. Negative scan in six other patients was thought to be associated with extensive inflammation and severe diarrhea. (3) Five of the twelve patients were observed before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Our laboratory investigated the use of a rapid miniaturized chromatography system, ITLC-SG with 0.9% NaCl, to assess the radiochemical purity of 111In labeled monoclonal antibodies (MoAbs). Radiochemical analysis was performed on numerous 111In labeled antibody preparations with labeling efficiencies ranging from 40 to greater than 95% and the results compared to those obtained with size exclusion high performance liquid chromatography (HPLC). The chromatographic procedure involved challenging radiolabeled antibodies with 0.05 M DTPA to chelate unbound and/or non-specific bound 111In, spotting on miniaturized instant thin layer-silica gel chromatography strips, developing in 0.9% NaCl, and counting appropriate segments for radioactivity. Results of the study demonstrated that the miniaturized chromatography procedure was rapid, taking less than 4 min to complete, and accurate in assessing the amount of unbound or non-specific bound 111In in 111In labeled monoclonal antibodies, when compared to size exclusion HPLC.

A general method is given to quantify the radioactivity ingested by a breast-fed infant following maternal radiopharmaceutical administration, and to derive the period to interrupt feeding which reduces the corresponding effective dose equivalent to below 1 mSv. Results are presented from applying the method to all available measurements of radioactivity secreted in breast milk. This review includes some hitherto unpublished data, takes more account of the scarcity of the available data, and has resulted in modifications to the guidance for interrupting breast feeding. Recommendations for interrupting feeding with mature milk have been expanded into four categories: (1) interruption not essential; (2) interruption for a fixed period of time; (3) interruption until measurements indicate feeding can be resumed; and (4) cease breast feeding. Changes to the earlier guidance are that 99Tcm-pertechnetate, (99Tcm) erythrocytes, 125I-OIH and 131I-OIH have been moved to the third category, and that recommendations have been included for 99Tcm-DMSA, 99Tcm-glucoheptonate, 99Tcm-HDP, 99Tcm-HMDP, 123I-iodide and 123I-OIH. Before recommendations (1) and (2) can be issued to a mother, quality control measurements must be made of the radiopharmaceutical administered. Recommendations (3) or (4) only should be issued to mothers secreting colostrum. If there are changes in the recommended dosimetry in the future, the calculated fractional ingested activities can be used as a basis to refine the recommendations.

HMFG1 tumour associated monoclonal antibody IgG1 and F(ab')2 fragments were radiolabelled with indium-111 and used to study patients with breast cancer. In vitro and in vivo stability of the radiolabelled antibodies was shown to be satisfactory. Thirty patients with primary breast cancer underwent tumour resection and quantitative evaluation of the radioactivity in the tumour and normal tissues following administration of specific and non-specific antibodies. The mean tumour uptake of HMFG1 F(ab')2 fragments at 24 h was significantly higher (P less than 0.05) than the intact IgG but at 48 h there was no difference. The mean tumour uptake with the specific antibody was higher than the non-specific antibody of the same subclass (P less than 0.05). Lymph node metastases showed higher antibody uptake than the corresponding primary tumours (P less than 0.05). Fifteen patients with primary or metastatic breast cancer were investigated by external body scintigraphy using HMFG1 F(ab')2 fragments. Successful localisation was observed in approximately 50% of the primary and metastatic lesions with no false positive results. All the patients had observable concentration of 111In in the liver (20% of the injected dose), the kidneys and the spleen. Following i.v. administration, F(ab')2 fragments cleared from the blood more rapidly than the intact IgG. We conclude that HMFG1 F(ab')2 fragments can localise specifically and faster than intact IgG in breast cancer but the sensitivity of the radioimmunoscintigraphy is relatively low. This method needs further improvement before becoming clinically useful for detecting and staging breast cancer.

The accumulation of an Indium-111-labeled monoclonal antibody (MoAb), ZME-018, in melanoma tumors in a patient was determined by sequential, quantitative gamma camera imaging. The amount and concentration of In-111 in each tumor changed in a characteristic pattern with time, reaching a peak at day 3 followed by a steady clearance. The concentration of In-111 in the tumor and the ratios of tumor to whole-body or blood decreased as the size of the tumor increased. These results were interpreted to indicate that the fraction of active, perfused tumor decreased as the melanoma lesions increased in size. The maximum number of MoAb molecules bound per melanoma cell was calculated to be abut 35,000. The implications of these observations for radioimmunoimaging and therapy are significant.