Radiation-absorbed dose estimates to normal organs following intraperitoneal 186Re-labeled monoclonal antibody: methods and results.

The radiation-absorbed dose was estimated following i.p. administration of a 186Re-labeled murine antibody, NR-LU-10, in 27 patients with advanced ovarian cancer. Data for the dosimetry estimation were obtained from quantitative gamma camera imaging and gamma counting of serum and i.p. fluid radioactivity. A peritoneal cavity model was used to estimate the dose to normal organs from radioactivity within the peritoneal cavity. Estimates of radiation-absorbed dose to normal organs in rad/mCi administered (mean + SD) were: whole body, 0.7 + 0.3; marrow, 0.4 + 0.1; liver, 1.9 + 0.9; kidneys, 0.2 + 0.2, and intestine, 0.2 + 0.2. The radiation-absorbed dose estimates to the normal peritoneal surface varied depending on the volume of fluid infused and whether the activity was measured by the gamma camera or from the peritoneal fluid samples. Using gamma camera data, the peritoneal surface dose ranged from 7 to 36 rads/mCi; when using the peritoneal fluid sample data, the dose ranged from 2 to 25 rads/mCi. Myelosuppression, observed in several patients, correlated best with marrow dose estimates based on the serum radioactivity, and significant toxicity was observed at marrow doses greater than 100 rads. The noninvasive methods of dose estimation for i.p. administration of radioimmunoconjugates provided reasonable absorbed dose estimates when compared with previously described, more invasive methods.

Pretargeted radioimmunotherapy (PRIT) for treatment of non-Hodgkin's lymphoma (NHL).

Pretargeted radioimmunotherapy (PRIT) was first investigated in a series of phase I and phase II studies in patients with adenocarcinoma using a pancarcinoma antibody, NR-LU-10. The principles and schema developed were then applied to an initial study in patients with non-Hodgkin's lymphoma (NHL). The PRIT approach used is a multi-step delivery system in which an antibody is used to target streptavidin to a tumor-associated antigen receptor, and subsequently, biotin is used to target the 90Y radioisotope to the tumor localized streptavidin. In the NHL study, a chimeric, IgG1, anti-CD20 antibody (Rituximab) was conjugated to streptavidin (SA) and administered to patients. Thirty-four hours later, a clearing agent, synthetic biotin-N-acetyl-galactosamine, was administered to remove non-localized conjugate from the circulation. Finally, a DOTA-biotin ligand, labeled with 111In for imaging and/or 90Y for therapy was administered. Ten patients with relapsed or refractory NHL were studied, and seven received 30 or 50 mCi/m(2) 90Y DOTA-biotin. Preliminary studies using 186Re labeled conjugate confirmed that it localized to tumor and that the clearing agent removed >95% of the conjugate from the circulation. Radiolabeled biotin localized well to tumor. Unbound radiobiotin was rapidly excreted from the whole body and normal organs. The mean tumor dose calculated was 29+/-23 cGy/mCi 90Y, and the mean tumor to whole body dose ratio was 38:1. Only grade I/II non-hematologic toxicity was observed. Hematologic toxicity was also not severe; i.e. five of the seven patients who received 30 or 50 mCi/m(2) of 90Y-DOTA-biotin experienced only transient grade III (but no grade IV) hematologic toxicity. Although six of 10 patients developed humoral immune responses to the streptavidin, these were delayed and transient and hence may not preclude retreatment. Six of seven patients who received 30 or 50mCi/m(2) 90Y achieved objective tumor regression, including three complete and one partial response. The estimate of tumor to whole body dose ratio (38:1) achieved with PRIT in these NHL patients is higher than that achieved in other studies using conventional RIT. Toxicity was mild and tumor response encouraging. PRIT clearly deserves additional study in patients with NHL.

Breast milk excretion of radiopharmaceuticals: mechanisms, findings, and radiation dosimetry.

The excretion of radiopharmaceuticals in breast milk is studied to understand excretion mechanisms and to determine recommended breast feeding interruption times for many compounds based on the radiation absorbed dose estimated. A literature review is summarized, providing information on breast milk excretion of many radiopharmaceuticals, including the observed fractions of administered activity excreted and the disappearance half-times. Radiation doses to the infant and to the mother's breasts have been calculated using mathematical models of the activity clearance into milk, with interruption schedules for the nursing infant derived using a dose criteria of 1 mSv effective dose to the infant. In only 9 of the 25 radiopharmaceuticals considered here is interruption in breast feeding thought necessary. However, in the literature, breast milk concentrations of radiopharmaceuticals and half-times varied considerably between subjects, and individual measurements are encouraged to raise confidence in specific cases. The absorbed dose to the mother's breast approaches 10-20 mGy (1-2 rad) for a few nuclides, but most doses are quite low. Therapeutic administration of 131I-NaI is a special case, for which the breast dose for a 5550 MBq (150 mCi) administration could approach 2 Gy (200 rad). In this article, these data are discussed, with the aim of assisting others in evaluating the significance of administration of radiopharmaceuticals to lactating women. An example of a sampling scheme and calculation to determine dose for a specific patient is also developed.

Marrow toxicity and radiation absorbed dose estimates from rhenium-186-labeled monoclonal antibody.

UNLABELLED: Estimates of radiation absorbed dose to the red marrow (RM) would be valuable in treatment planning for radioimmunotherapy if they could show a correlation with clinical toxicity. In this study, a correlation analysis was performed to determine whether estimates of radiation absorbed dose to the bone marrow could accurately predict marrow toxicity in patients who had received 186Re-labeled monoclonal antibody. METHODS: White blood cell and platelet count data from 25 patients who received 186Re-NR-LU-10 during Phase I radioimmunotherapy trials were analyzed, and the toxicity grade, the fraction of the baseline counts at the nadir (percentage baseline) and the actual nadir were used as the indicators of marrow toxicity. Toxicity was correlated with various predictors of toxicity. These predictors included the absorbed dose to RM, the absorbed dose to whole body (WB) and the total radioactivity administered. RESULTS: Percentage baseline and grade of white blood cells and platelets all showed a moderate correlation with absorbed dose and radioactivity administered (normalized for body size). The percentage baseline platelet count was the indicator of toxicity that achieved the highest correlation with the various predictors of toxicity (r = 0.73-0.79). The estimated RM absorbed dose was not a better predictor of toxicity than either the WB dose or the total radioactivity administered. There was substantial variation in the blood count response of the patients who were administered similar radioactivity doses and who had similar absorbed dose estimates. CONCLUSION: Although there was a moderately good correlation of toxicity with dose, the value of the dose estimates in predicting toxicity is limited by the patient-to-patient variability in response to internally administered radioactivity. In this analysis of patients receiving 186Re-labeled monoclonal antibody, a moderate correlation of toxicity with dose was observed but marrow dose was of limited use in predicting toxicity for individual patients.

Contribution to red marrow absorbed dose from total body activity: a correction to the MIRD method.

UNLABELLED: The contribution to red marrow absorbed dose from beta-emitting radionuclides distributed uniformly in the total body can be overestimated using either MIRD 11 or MIRDOSE3. The S value assigned to the red marrow target region from activity distributed in the remainder of the body is of particular concern. The assumption that the specific absorbed fraction for total body irradiating red marrow and other skeletal tissues is the inverse of the total-body mass can result in an inappropriate remainder-of-body contribution to marrow dose. We evaluated differences in the calculation of marrow dose using MIRD 11 and MIRDOSE3 formulations and developed methods to correct the results from either to remove inappropriate contributions. When bone takes up significantly less activity than is predicted from an apportionment of remainder-tissue activity based on mass, the standard remainder-of-body correction may substantially overestimate the electron component of the S value from remainder tissues to red marrow using either MIRD 11 or MIRDOSE3. If bone takes up activity, this contribution is negligible using MIRD 11 S values but remains with MIRDOSE3 S values. This overestimate can be significant, particularly when the residence time of activity in the remainder of the body is much higher than in the red marrow and a different correction is needed. As the ratio of the remainder of body to marrow residence time is lowered, the overestimate becomes less significant. CONCLUSION: In this article, we show the magnitude of this overestimate (which is most important for nuclides with large "nonpenetrating" emission components and for pharmaceuticals that have a large ratio of remainder of body to marrow residence times), show the appropriate corrections to be made in each case, and propose a new method for calculating marrow dose contributions that will avoid this complication in future applications. Because all models give approximate doses for real patients, with uncertainties within those involved in these corrections, we do not suggest that changes be made to existing marrow dose estimates. We suggest only that future calculations be as accurate as possible.

Dosimetry of rhenium-186-labeled monoclonal antibodies: methods, prediction from technetium-99m-labeled antibodies and results of phase I trials.

Rhenium-186 is a beta-emitting radionuclide that has been studied for applications in radioimmunotherapy. Its 137 keV gamma photon is ideal for imaging the biodistribution of the immunoconjugates and for obtaining gamma camera data for estimation of dosimetry. Methods used for determining radiation absorbed dose are described. We have estimated absorbed dose to normal organs and tumors following administration of two different 186Re-labeled immunoconjugates, intact NR-LU-10 antibody and the F(ab')2 fragment of NR-CO-02. Tumor dose estimates in 46 patients varied over a wide range, 0.4-18.6 rads/mCi, but were similar in both studies. Accuracy of activity estimates in superficial tumors was confirmed by biopsy. Prediction of 186Re dosimetry from a prior 99mTc imaging study using a tracer dose of antibody was attempted in the NR-CO-02 (Fab')2 study. Although 99mTc was an accurate predictor of tumor localization and the mean predicted and observed radiation absorbed doses to normal organs compared favorably, 186Re dosimetry could not be reliably predicted in individual patients. The methods described nevertheless provide adequate estimates of 186Re dosimetry to tumor and normal organs.

Pharmacokinetics and normal organ dosimetry following intraperitoneal rhenium-186-labeled monoclonal antibody.

UNLABELLED: Pharmacokinetics, biodistribution and radiation dose estimates following intraperitoneal administration of a 186Re-labeled murine antibody, NR-LU-10, were assessed in 27 patients with advanced ovarian cancer. METHODS: Quantitative gamma camera imaging and gamma counting of serum and intraperitoneal fluid radioactivity were used to obtain data for dosimetry estimation. The MIRD intraperitoneal model was used to estimate dose to normal organs from radioactivity within the peritoneal cavity. The absorbed dose to normal peritoneum was estimated in two ways: from the gamma camera activity and peritoneal fluid samples. RESULTS: Serum activity peaked at 44 hr and depended on the concentration of radioactivity in the peritoneal fluid. Mean cumulative urinary excretion of 186Re was 50% by 140 hr. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean +/- s.d.) were whole body 0.7 +/- 0.3; marrow 0.4 +/- 0.1; liver 1.9 +/- 0.9; lungs 1.3 +/- 0.7; kidneys 0.2 +/- 0.2; intestine 0.2 +/- 0.2. Peritoneal surface dose estimates varied depending on the volume of fluid infused and the method of dose determination. Using gamma camera data, the peritoneal dose ranged from 7 to 36 rad/mCi. Using peritoneal fluid sample data, the dose ranged from 2 to 25 rad/mCi. Significant myelosuppression was observed at marrow doses above 100 rad. CONCLUSION: Noninvasive methods of dose estimation for intraperitoneal administration of radioimmunoconjugates provide reasonable estimates when compared with previously described methods.

Clinical optimization of pretargeted radioimmunotherapy with antibody-streptavidin conjugate and 90Y-DOTA-biotin.

UNLABELLED: Pretargeted radioimmunotherapy (PRIT) was evaluated using an antibody-streptavidin conjugate, followed by a biotin-galactose-human serum albumin clearing agent and 90Y-dodecane tetraacetic acid (DOTA)-biotin as the final step for therapy. The objective was to develop a clinical protocol that could show an improved tumor-to-red marrow therapeutic ratio compared with conventional radioimmunotherapy (RIT) and at the same time preserve the efficiency of tumor targeting. METHOD: Forty-three patients with adenocarcinomas reactive to NR-LU-10 murine monoclonal antibody received the 3 components. Doses and timing parameters were varied to develop an optimized schema. In some patients, the conjugate was radiolabeled with 186Re as an imaging tracer to assess biodistribution of the conjugate and effectiveness of the clearing agent. 111In-DOTA-biotin was coinjected with 90Y-DOTA-biotin for quantitative imaging. Safety, biodistribution, pharmacokinetics, dosimetry, and antiglobulin formation were evaluated. RESULTS: The optimal schema was defined as a conjugate dose of 125 microg/mL plasma volume followed at 48 h by a clearing agent in a 10:1 molar ratio of clearing agent to serum conjugate. The therapeutic third step was 0.5 mg radiobiotin administered 24 h later. No significant adverse events were observed after administration of any of the components. The mean tumor-to-marrow absorbed dose ratio when using the optimized PRIT schema was 63:1, compared with a 6:1 ratio reported previously for conventional RIT. Antiglobulin to murine antibody and to streptavidin developed in most patients. CONCLUSION: This initial study confirmed that the PRIT approach is safe and feasible and achieved a higher therapeutic ratio than that achieved with conventional RIT using the same antibody.

Rhenium-186-labeled chimeric antibody NR-LU-13: pharmacokinetics, biodistribution and immunogenicity relative to murine analog NR-LU-10.

A mouse-human chimeric monoclonal antibody (NR-LU-13), with the same pancarcinoma antigen recognition site as a previously studied murine monoclonal antibody (NR-LU-10), was radiolabeled with 186Re using a bifunctional chelate. Nine patients (ages 31-81 yr) with metastatic adenocarcinoma received 186Re NR-LU-13. A single intravenous dose of 42 mg NR-LU-13 labeled with 25 mCi/m2 (two patients) or 60 mCi/m2 (seven patients) was administered. Mean serum disappearance half-time values for the chimeric 186Re NR-LU-10). Fifty percent of the radiolabel was excreted in the urine by 6 days. Tumor localization was demonstrated by gamma camera imaging in seven of nine patients. The percent injected dose per gram in a single tumor biopsy specimen was 0.003% at 72 hr postinjection. Absorbed dose to bone marrow was 1.5 +/- 0.7 rads/mCi and resulted in reversible myelosuppression in five of six evaluable patients who received 60 mCi/m2: median WBC nadir = 2500/microliters; median platelet nadir = 85,500/microliters. Low grade fever, nausea, slight elevations of liver function tests and mild allergic reactions were seen in some patients. The chimeric antibody elicited low levels of anti-NR-LU-13 antibody in six of eight evaluable patients (75%), in contrast to NR-LU-10 which elicited higher levels of human anti-mouse antibody in all patients. This pilot study demonstrates the ability of the chimeric antibody to target tumors with reduced (but not absent) immunogenicity and delayed clearance relative to the murine antibody.

Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials.

Rhenium is a radionuclide with physical and chemical properties suitable for radioimmunotherapy. Two Phase I trials were carried out using 186Re-labeled murine monoclonal antibodies. Patients with refractory metastatic epithelial carcinoma received single doses of either 186Re-labeled intact NR-LU-10, a pancarcinoma antibody, 25-120 mCi/m2 (n = 15) or 186Re-labeled F(ab')2 fragment of NR-CO-02, an anti-CEA variant antibody, 25-200 mCi/m2 (n = 31). Prior to radioimmunotherapy, tumor localization of antibody was confirmed by 99mTc-labeled NR-LU-10 Fab or 99mTc-labeled NR-CO-02 F(ab')2 imaging. Dose-limiting myelosuppression was observed at 120 mCi/m2 following 186Re-NR-LU-10 intact antibody and at 150 mCi/m2 following NR-CO-02 F(ab')2 fragment in heavily pretreated patients. In patients with minimal prior therapy, a maximum tolerated dose for NR-CO-02 F(ab')2 was not reached by 200 mCi/m2. Non-marrow toxicity was minimal. Human anti-mouse antibody developed in all patients receiving intact NR-LU-10, and in 86% patients receiving F(ab')2 NR-CO-02. One patient treated with 186Re NR-CO-02 achieved a partial response. We conclude that 186Re-labeled antibody can be safely administered with significant toxicity limited to marrow.

Imaging lung cancer with radiolabeled antibodies.

Radiolabeled antibodies have been studied by several investigators as to their potential role in the diagnosis and staging of lung cancer. Studies with indium-111-labeled antibodies in limited numbers of patients have shown that 75% to 100% of primary lung tumors can be delineated and that the detection of metastases is dependent on size and location. Hepatic metastases and lesions smaller than 2 cm frequently are not visualized. Other studies with a technetium-99m-labeled Fab fragment of NR-LU-10 have been carried out for the staging of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In a large, well controlled multicenter study of patients with SCLC, staging by antibody imaging alone was as accurate as a combination of the conventional staging tests, and the positive predictive value for antibody staging of extensive disease was greater than 95%. In patients with NSCLC, antibody imaging was comparable to computed tomography for staging the mediastinum and was able to identify distant metastases at the same time.

Dosimetry of solid tumors.

Dosimetry data arising from a decade of radioimmunotherapy are summarized along with techniques utilized to arrive at the reported dose estimates. Generality of the MIRD methodology allows it to serve as a vehicle for the calculation of solid tumor dosimetry although several limitations exist. Nonstandard geometries of solid tumors will ultimately necessitate determination of absorbed fractions for the individual tumors. Several approaches currently under investigation are described. For reasons of practicality, solid tumor dosimetry estimates continue to use the assumption of homogeneous activity distribution in a source organ, accounting for either all radiation or only nonpenetrating radiation. As computation tools become available for incorporating inhomogeneous cellular level data, the currently used "average dose" as an index of tumor sterilization will likely be replaced with a statistical distribution based on the number of viable cells in the tumor volume. Estimates of a tumor control dose would be based upon a linear extension of dose coupled with a threshold dose for cell sterilization.

Pretargeted radioimmunotherapy (PRIT) for treatment of non-Hodgkin's lymphoma (NHL): initial phase I/II study results.

Pretargeted radioimmunotherapy (PRIT) was investigated in patients with non-Hodgkin's lymphoma (NHL). The PRIT approach used in this study is a multi-step delivery system in which an antibody is used to target streptavidin to a tumor associated antigen receptor, and subsequently biotin is then used to target 90Y radioisotope to the tumor localized streptavidin. A chimeric, IgG1, anti-CD20 antibody, designated C2B8 or Rituximab, was conjugated to streptavidin (SA) and administered to patients with NHL. Thirty-four hours later, a clearing agent, synthetic biotin-N-acetyl-galactosamine, was administered to remove non-localized conjugate from the circulation. Finally, a DOTA-biotin ligand, labeled with 111In for imaging and/or 90Y for therapy was administered. Ten patients with relapsed or refractory NHL were studied. In three patients, the C2B8/SA conjugate was radiolabeled with a trace amount of 186Re in order to assess pharmacokinetics and biodistribution using gamma camera imaging. Seven patients received 30 or 50 mCi/m2 90Y DOTA-biotin. Re-186 C2B8/SA images confirmed that the conjugate localized to known tumor sites and that the clearing agent removed > 95% of the conjugate from the circulation. Radiolabeled biotin localized well to tumor. Unbound radiobiotin was rapidly excreted from the whole body and normal organs. The mean tumor dose calculated was 29 +/- 23 cGy/mCi 90Y and the average whole body dose was 0.76 +/- 0.3 cGy/mCi 90Y, resulting in a mean tumor to whole body dose ratio of 38:1. Only grade I/II non-hematologic toxicity was observed. Hematologic toxicity was also not severe; i.e., five of the seven patients who received 30 or 50 mCi/m2 of 90Y-DOTA-biotin experienced only transient grade III (but no grade IV) hematologic toxicity. Although six of ten patients developed humoral immune responses to the streptavidin, these were delayed and transient and hence may not preclude retreatment. Six of seven patients who received 30 or 50mCi/m2 90Y achieved objective tumor regression, including three complete and one partial response. The estimate of tumor to whole body dose ratio (38:1) achieved with PRIT in these NHL patients is higher than has been achieved in other studies using conventional RIT. Toxicity was mild and tumor response encouraging. PRIT clearly deserves additional study in patients with NHL.

Radiation absorbed dose estimation for 90Y-DOTA-biotin with pretargeted NR-LU-10/streptavidin.

UNLABELLED: Pretargeted radioimmunotherapy permits the administration of doses of 90Y five times higher than is possible with antibodies directly labeled with 90Yttrium (90Y). These high doses of 90Y introduced new issues for dosimetry that were not encountered in prior studies using conventional radioimmunotherapy. We have addressed these issues here and correlated dosimetry estimates with observed toxicity and tumor responses. METHODS: The pretargeted radioimmunotherapy (PRIT) system employed the antibody NR-LU-10 conjugated with streptavidin, a glycoprotein clearing agent and 90Y-DOTA-biotin. A single dose of 90Y was escalated to 140 mCi/m2. Indium-111(111In) (3-5 mCi) DOTA-biotin was co-injected for gamma camera imaging and dosimetry assessment. The effect of bremsstrahlung radiation from increasing 90Y activity levels with a constant dose of 111In was studied using a phantom. Patient images identified the intestinal tract and the kidneys as potential organs at risk of clinically significant radiation toxicity. A method of measuring the activity localized in the intestinal tract was developed, and S values were calculated to estimate intestinal wall dose from radioactivity present in the intestine. Intestinal, bone marrow and renal toxicity were observed. Coefficients were derived for correlating the relationships between observed intestinal and marrow toxicity and the estimated radiation absorbed doses. RESULTS: At an 90Y:111In ratio of 50:1, bremsstrahlung radiation accounted for 12% of the counts in the images. Grade IV diarrhea was observed in patients estimated to have received 6850-14,000 cGy to the large intestinal wall. The correlation coefficient of intestinal toxicity with absorbed dose was 0.64. Myelotoxicity (measured as grade of suppression of absolute neutrophil count) correlated better with marrow dose (r = 0.72) than with the whole body dose, (r = 0.44). Delayed renal toxicity was observed in two patients 8 and 11 months following therapy. Tumor response was seen in the two patients with the highest estimated dose to tumor, 4,000-6,000 cGy. CONCLUSION: Dosimetry is feasible using 111In as a tracer in the presence of high 90Y activity. The absorbed dose estimates derived in the PRIT schema correlated moderately well with clinically observed toxicity and response.

Localization of inflammation with 111In IgG and 99Tcm albumin colloid labelled leukocytes in a rabbit model.

Localization of inflammation with two recently described radiotracers, 111In-labelled polyclonal IgG and 99Tcm albumin colloid labelled leukocytes (Tc-WBC), was studied. Accumulation of activity was compared with 111In-labelled leukocytes (In-WBC) using 131I human serum albumin as a control. Ratios of activity in a chemically induced abscess in the thigh of rabbits compared with normal muscle tissue were measured. The results showed that all agents localize in inflammation but Tc-WBC consistently localizes to a greater degree than the other agents. At 2 h the inflammed-to-normal ratios for Tc-WBC were 4, IgG 2.1, albumin 1.9 and In-WBC 1.7. The pattern of the ratios remained similar over the 18 h period of the study. The short time in which leukocytes can be labelled and the quality of the images obtained suggest that Tc-WBC imaging is the method of choice for this model.

Cardiac calcification causing arrhythmia detected by technetium-99m MDP and SPECT.

SPECT was used to identify a focal accumulation of cardiac calcification using Tc-99m MDP in a patient with an arrhythmia and known metastatic calcification elsewhere.

Clinical experience with Tc-99m nofetumomab merpentan (Verluma) radioimmunoscintigraphy.

Tc-99m nofetumomab merpentan (Verluma), consisting of a Fab fragment of the pancarcinoma murine antibody NR-LU-10, has been previously evaluated as a diagnostic imaging agent in staging patients with lung cancer. The authors have taken advantage of the pancarcinoma reactivity of this antibody to select patients with a variety of carcinomas for radioimmunotherapy trials. These have included gastrointestinal, breast, ovary, pancreas, kidney, cervix, and bladder carcinoma. This article documents the range of tumor types and locations that can be identified by gamma camera imaging with this radioimmunoconjugate. Tumor was positively identified in 92% of 107 patients studied. In 15 patients, the images led to suspicion of previously unknown disease. The authors conclude that this radioimmunoconjugate is useful in assessing patients with advanced disease. Additional studies may be warranted to explore further the potential benefit of this diagnostic imaging agent in evaluating the extent of disease in patients with a variety of carcinomas.

Pleuroperitoneal communication associated with malignant ascites. A potential cause for new pleural effusion suggestive of pulmonary embolism.

A patient with metastatic gastric carcinoma and malignant ascites developed sudden-onset dyspnea secondary to a new large left pleural effusion. A radionuclide lung scan performed for suspected pulmonary embolism was indeterminate. Scintigraphy performed following intraperitoneal administration of Tc-99m sulfur colloid subsequently demonstrated rapid accumulation of activity in the left pleural space, indicating the presence of a pleuroperitoneal communication. In a patient with known or suspected ascites, a new pleural effusion, and an indeterminate lung scan, peritoneal scintigraphy may identify the origin of the effusion and obviate the need for further invasive evaluation for possible pulmonary embolism.

Progressive pulmonary calcification complicating successful renal transplantation.

Metastatic pulmonary calcification occurs in a chronic form in patients with malignancy, chronic renal failure, and primary hyperparathyroidism. A rapidly progressive form is associated with renal transplant failure. This case report describes chronic progressive pulmonary calcification after successful transplant with no obvious underlying cause.