Patient dosimetry of intravenously administered 99mTc-annexin V.

UNLABELLED: Annexin V labeled with 99mTc is evaluated as a potential in vivo marker for tissue with increased apoptosis. Promising results in patients have been obtained with 99mTc-(n-1-imino-4-mercaptobutyl)-annexin V (99mTc-i-AnxV). Because information on biodistribution and radiation burden is desired for the application of any radiopharmaceutical, a dosimetric study of 99mTc-i-AnxV was undertaken. METHODS: Eight persons with normal kidney and liver functions were included in this study: six patients with myocardial infarction, one with Crohn's disease, and one healthy volunteer. Approximately 600 MBq 99mTc-i-AnxV were injected intravenously immediately before a dynamic study with a dual-head gamma camera in conjugate view mode. In the next 24 h, two to four whole-body scans were acquired. Patient thickness was determined from a transmission scan with a 57Co flood source. Organ uptake was estimated after correction for background, attenuation, and scatter, using a depth-independent buildup factor and an organ-size-dependent attenuation correction. Residence times were calculated from the dynamic and whole-body studies and used as input for the MIRDOSE 3.1 program to obtain organ-absorbed doses and effective dose. RESULTS: Activity strongly accumulated in the kidneys (21% +/- 6% of the injected dose at 4 h postinjection) and the liver (12.8% +/- 2.2%). Uptake in the target tissues (myocardium or colon) was limited and negligible from a dosimetric point of view. The biologic half-life of activity registered over the total body was 62 +/- 13 h. Of the excreted activity, approximately 75% went to the urine and 25% to the feces. The absorbed dose for the more strongly exposed organs was (in microGy/MBq): kidneys, 93 +/- 24; spleen, 22 +/- 6; liver, 17 +/- 2; testes, 15 +/- 3; thyroid, 10 +/- 6; urinary bladder wall, 7.5 +/- 2.6; and red bone marrow, 5.5 +/- 0.8. The effective dose was 9.7 +/- 1.0 microSv/MBq, corresponding to a total effective dose of 5.8 +/- 0.6 mSv for a nominally injected activity of 600 MBq. CONCLUSION: 99mTc-i-AnxV strongly accumulates in the kidneys and to a lesser degree in the liver. The associated effective dose per MBq is in the midrange of values found for routine 99mTc-labeled compounds. From a dosimetric point of view 99mTc-i-AnxV is therefore well suited for the study of apoptosis in patients.

99mTc-PEG liposomes for the scintigraphic detection of infection and inflammation: clinical evaluation.

UNLABELLED: Polyethyleneglycol (PEG) liposomes have been shown to be excellent vehicles for scintigraphic imaging of infection and inflammation in various experimental models. In this article we report on a series of patients with possible infectious and inflammatory disease in whom the performance of 99mTc-PEG liposomes was evaluated. The results of 99mTc-PEG liposome scintigraphy were directly compared with those of 111In-immunoglobulin G (IgG) scintigraphy. METHODS: Thirty-five patients (22 men, 13 women; mean age, 51 y; range, 20-76 y), suspected of having infectious or inflammatory disease, received 740 MBq 99mTc-PEG liposomes intravenously. Imaging was performed at 4 and 24 h after injection. Patients received 75 MBq 111In-IgG 24 h after administration of the liposomes. The scintigraphic results were compared and verified by culture, biopsy, surgery, and follow-up of at least 6 mo. RESULTS: Of the 16 proven infections and inflammations, 15 were detected by 99mTc-PEG liposome scintigraphy: soft-tissue infection (n = 3), septic arthritis (n = 3), autoimmune polyarthritis (n = 2), infected hip prosthesis (n = 1), infected osteosynthesis (n = 1), spondylodiscitis (n = 1), infected aortic prosthesis (n = 1), colitis (n = 1), abdominal abscess (n = 1), and pneumonia (n = 1). 99mTc-PEG liposome and 111In-IgG scintigraphy both missed 1 case of endocarditis. In addition, an 111In-IgG scan of a patient with mild soft-tissue infection was false-negative. Concordantly false-positive scans were recorded from 2 patients, both with uninfected pseudarthrosis and focal signs of sterile inflammation. During liposomal administration, 1 patient experienced flushing and chest tightness, which rapidly disappeared after lowering the infusion rate. No other adverse events were observed. CONCLUSION: This clinical evaluation of 99mTc-PEG liposomes shows that focal infection and inflammation can be adequately imaged with this new agent. The performance of 99mTc-PEG liposomes is at least as effective as that of 111In-IgG. With the simple and safe preparation and the physical and logistic advantages of a 99mTc label, 99mTc-PEG liposomes could be an attractive agent for infection or inflammation imaging.

Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250.

Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG250) in renal cell carcinoma (RCC) patients indicated the potential use of this antibody for radioimmunotherapy. Here we report on a phase I activity dose escalation study to determine the safety, the maximum tolerable dose (MTD), and the possible therapeutic potential of 131I-labeled cG250 in patients with progressive metastatic RCC. All patients (n = 12) received a diagnostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of 131I. If accumulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 labeled with a high dose of 131I was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m2. If no dose-limiting toxicity occurred, the study continued at the next dose level (555 MBq/m2 increase). Most patients experienced mild nausea without vomiting. No other complaints were reported during hospitalization. In two of two patients who received a dose of 2775 MBq/m2, grade IV hematological toxicity was observed, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq/m2. In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) was achieved, whereas another patient (2220 MBq/m2) showed a partial response that is ongoing (>9 months). The minor responses observed in this phase I trial in patients with an advanced stage of RCC are encouraging and warrant further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.

Absolute organ activity estimated by five different methods of background correction.

UNLABELLED: Accurate absorbed dose estimates in radionuclide therapy require patient-specific dosimetry. In patient-based dosimetry, estimation of absolute organ uptake is essential. The methods used should be reasonably accurate as well as easy to perform in routine clinical practice. One of the major sources of uncertainty in quantification of organ or tumor activity from planar images is the activity present in the tissue surrounding the source. METHODS: To estimate organ activity as a function of organ-to-background activity concentration ratio, a cylindrical phantom, filled with 5.6 liters of water was used to simulate the abdomen of a patient. Two other cylinders of 150 ml each, representing the kidneys, were each filled with 19 MBq 99mTC and were positioned in the abdomen phantom. The phantom was imaged with a dual-head gamma camera with the kidneys placed at posterior depths of 1-, 5- and 10-cm at kidney-to-background activity concentration ratios of infinity, 10:1, 5:1 and 2:1. The conjugate view geometric mean counting method was used to quantify activity. Five methods for background correction were applied: (1) no correction; (2) conventional background correction (simple subtraction of the background counting rate from the source region counting rate); (3) Kojima method (background corrected for organ thickness and depth); (4) Thomas method (analytical solution); and (5) Buijs method (background corrected for organ and total-body thickness). RESULTS: Since the results were identical for both kidneys, only the left kidney activity measurements are presented. The accuracy of the five background correction methods is given as the percentage difference between the actual and measured activity in the left kidney. For Method 1, the percentage difference ranged from 2% with an infinite kidney-to-background activity concentration ratio to +413% with a 2:1 ratio. For Method 2, these values ranged from -1% to -80%, for Method 3 from +11% to -18%, for Method 4 from -2% to +120% and for Method 5 from -4% to +39%. CONCLUSION: Even though quantitative SPECT is the most rigorous method for activity quantification in conditions of low organ-to-background activity concentration ratio, planar scintigraphy can be applied accurately if appropriate attention is paid to background correction. Using relatively simple background subtraction methods, the quantitative planar imaging technique can result in reasonably accurate activity estimates (Methods 3 and 5). The use of Kojima's method is preferable, especially at very low source-to-background activity concentration ratios.

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration.

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.

Dynamic distribution and dosimetric evaluation of human non-specific immunoglobulin G labelled with 111In or 99Tcm.

This study presents data on the dynamic distribution and dosimetry of 111In- and 99Tcm-labelled human non-specific immunoglobulin G (IgG), two recently developed radiopharmaceuticals for the detection of infection and inflammation. Five healthy volunteers were injected with 20-75 MBq 111In-IgG and seven patients were injected with 740 MBq 99Tcm-hydrazinonicotinamide derivative (HYNIC)-IgG. Blood samples, urine and feces were collected. Whole-body gamma camera imaging studies were performed. The activity in source organs was quantified using the conjugate view counting method and a partial background subtraction technique. Dosimetric calculations were performed using the MIRD technique. For 111In-IgG, the mean biological half-times in the blood were 0.90 and 46 h for the a- and b-phase, respectively. For 99Tcm-HYNIC-IgG, these half times were 0.46 and 45 h. For 111In-IgG, the mean cumulative urinary excretion in the first 48 h was 18% of the injected dose, while excretion in the feces was less than 2% of the injected dose. For 99Tcm-HYNIC-IgG, the whole-body retention was always 100% up to 24 h. The mean absorbed doses in the liver, spleen, kidneys, red marrow and testes from 111In-IgG were 0.8, 0.7, 1.2, 0.3 and 0.4 mGy MBq-1 respectively. The mean absorbed doses for 99Tcm-HYNIC-IgG to these organs were 16, 24, 15, 10 and 22 mu Gy MBq-1 respectively. The mean effective dose was 0.25 mSv MBq-1 and 8.4 mu Sv MBq-1 for 111In-IgG and 99Tcm-HYNIC-IgG respectively. In conclusion, the radiation absorbed doses for both 111In-IgG and 99Tcm-HYNIC-IgG are low and, therefore, these radiopharmaceuticals can be administered safely from a radiation risk perspective.

Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250.

PURPOSE: Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody. PATIENTS AND METHODS: Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. RESULTS: In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients. CONCLUSION: 131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.

Dosimetry and risk estimates of radioiodine therapy for large, multinodular goiters.

UNLABELLED: In patients with a large, multinodular goiter (> 100 g), radiation absorbed doses in the thyroid, surrounding tissues and remainder of the body were estimated after therapeutic administration of 131I(3.7 MBq or 100 microCi/g of thyroid tissue retained at 24 hr). METHODS: Thermoluminescent dosimeter (TLD) measurements were performed on 23 patients (12 euthyroid and 1I hyperthyroid; thyroid weight 222 +/- 72 g; 2.1 +/- 0.9 GBq 131I) on the skin over the thyroid, over the submandibular gland and over the parotid gland. Thyroid radioactivity measurements were done daily in 6 euthyroid and 6 hyperthyroid patients (thyroid weight 204 +/- 69 g; 1.9 +/- 0.9 GBq 131I). An iodine biokinetic model and the MIRD methodology were used to estimate absorbed doses in organs. Cancer risks were calculated using ICRP Publication 60. RESULTS: Cumulated absorbed doses on the skin (TLD measurements) were 4.2 +/- 1.4 Gy (thyroid), 1.2 +/- 0.6 Gy (submandibular) and 0.4 +/- 0.2 Gy (parotid). All these values were significantly correlated with the amount of radioiodine retained in the thyroid at 24 hr (euthyroid versus hyperthyroid not significant). Absorbed doses in the thyroid of 94 +/- 25 Gy for euthyroid and 93 +/- 17 Gy for hyperthyroid patients were calculated (thyroid radioactivity measurements). Extrathyroidal absorbed doses (means of 12 patients) were 0.88 Gy in the urinary bladder, 0.57 Gy in the small intestine, 0.38 Gy in the stomach, and ranged from 0.05 to 0.30 Gy in other organs (euthyroid versus hyperthyroid not significant). A 1.6% life-time risk of development of cancer outside the thyroid gland was calculated. When applied to people of 65 yr and older the estimated risk is approximately 0.5%. CONCLUSION: These data may help in choosing the treatment regimen for individual patients with a large, multinodular goiter, who have to be treated for hyperthyroidism or compressive problems. In younger patients, surgery may be preferred. However, for elderly patients and patients with cardiopulmonary disease, the advantages of noninvasive radioiodine treatment will outweight the life-time risk of this mode of therapy.

The value of dynamic hepatic scintigraphy and serum aminoterminal propeptide of type III procollagen for early detection of methotrexate-induced hepatic damage in psoriasis patients.

Oral methotrexate (MTX) is a highly effective drug for the treatment of severe psoriasis. A limitation of this treatment is its potential hepatotoxicity. In the present prospective study the value of dynamic hepatic scintigraphy (DHS) and serum aminoterminal propeptide of type III procollagen (PIIINP) were investigated as screening methods for early detection of MTX-induced hepatic damage. These relatively non-invasive procedures were compared with the liver biopsy classification, until now the gold standard to assess MTX-induced liver damage. Twenty-five MTX patients were studied. The mean cumulative MTX dose was 3.9 g (range 0.2-11.1 g). Twenty-one patients had a normal liver histology (grade I), three patients had steatosis (grade II), and one patient mild fibrosis (grade IIIA). Seven additional patients with non-MTX related hepatic cirrhosis were included as disease controls. DHS showed a clear-cut separation between the portal contribution of the MTX patients with grade I liver histology, and that of all other patients. A portal contribution larger than 52% was associated with a > 95% chance of normal liver histology. If this cut-off value had been used to postpone the liver biopsy, this would have resulted in at least a 55% reduction in the number of biopsies in patients with a normal liver histology. DHS appeared to be very promising as a screening test to differentiate between the presence or absence of MTX-induced hepatic damage, but appeared not suitable to grade the severity of hepatic damage. Although a global relationship was demonstrated between serum PIIINP concentration and hepatic damage, single measurements in individual patients were not reliable. The combination of PIIINP measurements with DHS had only a limited additional value above DHS alone. The present study indicates that DHS has great promise for the detection of early MTX-induced hepatic damage. Pending further studies, regular liver biopsies remain mandatory for the safe prolonged use of MTX in psoriasis patients.

Measurement of mandibular bone density ex vivo and in vivo by dual-energy X-ray absorptiometry.

Severe bone resorption is a vexing clinical problem, especially in patients without teeth. To study resorption in vivo, measurements of bone mineral density (BMD) of the mandible of both patients with and without teeth are needed. Using a Hologic QDR-1000 bone densitometer designed to measure lumbar spine and hips, ex vivo and in vivo measurements were made in selected areas of the mandible. The mandible was positioned such that the X-ray beam was perpendicular to its sagittal plane. In this way the beam hits first one half of the mandible and then the other. The reproducibility--expressed as coefficient of variation--of the ex vivo measurements was 0.5%. For in vivo measurements this coefficient was 3%. The method used for mandibular BMD would make it possible to define an average BMD in several categories of the normal population and of patients, and to compare bone density in the mandible with that in the axial and perpendicular skeleton. Improvement may be obtained by repeating the measurement. The entrance dose per scan is low, equalling that of one bitewing/radiograph.

Intraoperative bone and bone marrow sampling: a simple method for accurate measurement of uptake of radiopharmaceuticals in bone and bone marrow.

Accurate estimation of bone marrow uptake of radiopharmaceuticals is of crucial importance for accurate whole body dosimetry. In this study, a method for obtaining normal bone marrow and bone during routine surgery without inconvenience to volunteers is suggested and compared to an indirect method. In five volunteers (group 1), 4 MBq 111In-labelled human polyclonal IgG (111In-IgG) was administered 48 h before placement of a total hip prosthesis. After resection of the femoral head and neck, bone marrow was aspirated from the medullary space with a biopsy needle. In five patients, suspected of having infectious disease (group 2), bone marrow uptake was calculated according to a well-accepted method using regions of interest over the lumbar spine, 48 h after injection of 75 MBq 111In-IgG. Bone marrow uptake in group 1 (4.5 +/- 1.3% D kg-1) was significantly lower than that in group 2 (8.5 +/- 2.1% D kg-1) (P < 0.01). Blood and plasma activity did not differ significantly for both groups. This method provides a system for directly and accurately measuring uptake and retention in normal bone marrow and bone of all radiopharmaceuticals at various time points. It is a safe and simple procedure without any discomfort to the patient. Since small amounts of activity are sufficient, the radiation dose to the patient is low.

Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bone mineral content.

The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval -36.0% to -8.1%) and cortical (-24.8%, 95% confidence interval -39.3% to -10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval -27.1% to -4.2%), but not the diaphyseal (-3.9%, 95% confidence interval -14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.

Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity.

BACKGROUND: Generalised osteoporosis is often described in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate disease related determinants of bone mineral density (BMD) in patients with RA. METHODS: Subjects were selected from a group of 147 patients with recent onset RA. Disease activity and functional capacity were studied prospectively in this cohort. Activity of the disease was assessed once every three months by various parameters, and functional capacity was measured with a health assessment questionnaire once every six months. Ninety seven patients consented to participate in the study. Bone mineral density was assessed with dual energy x ray absorptiometry in the lumbar spine, in a combined region of interest in the hips, and in Ward's triangle. Multiple linear regression procedures were used to analyse the data. RESULTS: Duration of RA was negatively associated with BMD at all three sites of measurement. The mean erythrocyte sedimentation rate in the six months before BMD measurement was negatively associated with BMD in the hip and in Ward's triangle. Other parameters of disease activity were not related to BMD. The mean health assessment questionnaire score in the 18 months before BMD measurement was negatively associated with BMD in the combined hip region only. Bone mineral density tended to be decreased when patients were compared with a normal reference group, especially in the femoral regions of interest. CONCLUSIONS: It is concluded that BMD may be affected in patients with recent onset RA by disease dependent mechanisms. Several factors have been suggested elsewhere as determinants of BMD in RA. The results of this study show that disease duration, disease activity, and functional impairment may, independently of each other, contribute to bone loss, especially in the proximal femur.

Dosimetric evaluation of immunoscintigraphy using indium-111-labeled monoclonal antibody fragments in patients with ovarian cancer.

This study reports the biodistribution and dosimetry for a monoclonal antibody against ovarian carcinoma. Eight patients received 140 MBq 111In-OV-TL 3 F(ab')2; thereafter gamma camera imaging was performed daily up to 96 hr. By using the conjugated view counting method, activity in the organs was quantitated by phantom calibration and by whole-body measurements using a whole-body counter with the conjugated view counting method. Red bone marrow uptake was derived from regions of interest over the lumbar vertebrae and iliac crest. In both methods, organ uptake varied only slightly with time, having a mean value of approximately 18%, 4%, 6% and 17% of the injected dose in the liver, spleen, kidneys and red bone marrow, respectively. The mean radiation dose to these organs was 0.9, 1.5, 1.2 and 0.5 mGy/MBq. The effective dose equivalent was 0.4 mSv/MBq. In this study, two different methods of uptake calculations, result in similar values of organ uptake.

Kinetics and biodistribution in relation to tumour detection with 111In-labelled OV-TL 3 F(ab')2 in patients with ovarian cancer.

The biological behaviour of 111In-labelled OV-TL 3 F(ab')2 was studied in 22 patients with suspected ovarian cancer. After i.v. injection with 140 MBq 111In-OV-TL 3 F(ab')2 (1 mg) blood samples were taken up to 96 h and urine and faeces were collected throughout the whole study. At surgery, 5 to 7 days post-injection, primary and metastatic tumour tissues, as well as fragments of several normal tissues, were removed and 111In uptake was measured. Blood activity disappeared with half-life values of 6.1 +/- 1.1 and 17.9 +/- 6.5 h. Within 96 h excretion in urine and faeces was 16.1 +/- 2.0% i.d. (mean +/- S.D.) and 3.1 +/- 1.9% i.d., respectively. Mean tissue uptake, expressed as % i.d. kg-1 was 3.9 +/- 1.0 for primary tumour, 11.5 +/- 5.0 for liver and 0.4 +/- 0.1 for several normal background tissues. Higher tumour uptake correlated with a higher detection rate at immunoscintigraphy. However, no strict correlation was found between the amount of tumour uptake and the expression of the monoclonal antibody defined OA3 antigen. Quantitation of organ activity, using region of interest analysis, resulted in mean peak organ activities for the liver of 16% i.d., spleen 9% i.d. and kidney 4% i.d. Distribution data indicate that besides specific antibody-antigen interaction several other mechanisms play a role in uptake in tumour and other tissues.