ORIGINAL 
Annals of Nuclear Medicine Vol. 4, No. 2, 55-58, 1990 
Bone scanning in patients with pleural effusion - Experience in 76 cases 
Shigeru KOSUDA Kunihiko YOKOYAMA,** Iku NISHIGUCHI,* Etsuo KUNIEDA,** Atsushi KUBO* and Shozo HASHIMOTO* 
*Department of Radiology, Tokyo Metropolitan Komagome Hospital **Keio University Hospital, Tokyo, Japan 
Seventy-six patients with malignant or benign pleural effusion were studied to determine the incidence of accumulation of 99mTc-MDP in relation to effusion, and reveal the mechanism. Of 76 patients, 46 (61%) were found to have diffuse uptake of 99mTc-MDP in the hemithorax, with almost the same positive rate in malignant and benign effusions, i,e. 62% and 57%, respectively. Of 46 patients, 32 (70%) showed diffuse, slight accumulation in the hemithorax, and the positive rate had a tendency to be higher with the increase in the effusion volume. 
We are convinced that the major mechanism of unilateral intrathoracic accumulation of 99mTc-MDP in pleural effusion is a passive transudation. 
Key words : bone scan, pleural effusion, 99mTc-MDP, 67Ga citrate 
INTRODUCTION 
UNILATERAL diffuse intrathoracic accumulation of bone seeking agents is not so uncommon because of the increasing use of these agents in osseous metastasis evaluation. There have been some reports as to the etiology of intrathoracic accumulation.1-3 Hy-perconcentration of 99mTc bone seeking agents in malignant effusion has also been reported previously.4-7 No investigator, however, has demonstrated the precise mechanism of accumulation of 99mTc bone seeking agents in pleural effusion. 
In our concern to disclose the mechanism, we reviewed the records of patients with pleural effusion due to miscellaneous diseases, who were referred to us for bone scanning during the previous four years. 
The aim of this research is to determine the incidence of accumulation of 99mTc-MDP in pleural effusion, and to attempt to reveal the mechanism. 
MATERIALS AND METHODS 
Bone scintigrams of 76 patients with malignant or benign pleural effusion, who were referred to us for bone scanning from January, 1983 through March, 1987, were analyzed. Of the 76 patients, 41 were male and 35 were female. Age range was 37 to 84 year (mean 59.8 year). All of the patients had definite, clinical and pathological documentation of pleural effusion at either side, when they underwent bone studies. The existence of pleural effusion was detected by radiographs, including CT scan, and/or thoracentesis. The final diagnosis was based on the results of cytology and/or culture or the clinical outcome. Malignant pleural effusion was proved cytologically from pleural fluid samples obtained in thoracentesis or thoracotomy. No patient had received radio-therapy or chemotherapy before the bone studies. Scans were performed approximately 3 hrs after i.v. injection of 740 MBq (20 mCi) of 99mTc-MDP on a gamma camera.* Both whole body and detailed spot views were taken in each case. We investigated the correlation between the presence of intrathoracic accumulation of 99mTc-MDP on bone scan and pleural effusion volume. The volume of pleural fluid was grossly estimated from the chest roentgenograms which were obtained within 1 week of the bone scans and mostly within 3 days. In the 46 out of 76 patients, 67Ga citrate scans were also available for comparison. Both anterior and posterior lung scans were made 48 hrs after i.v. injection of 111 MBq (3 mCi) of 67Ga citrate. Posterior spot views were taken in a patient lying prone, with the camera head facing down. 
RESULTS 
Tables 1, 2 and 3 show the results of our clinical examination. The positive rate of 99mTc-MDP accumulation in pleural effusion which resulted from miscellaneous diseases is shown on Table l. Of 76 patients with effusion, 46 (60.5%) were found to have diffuse uptake of 99mTc-MDP in the hemithorax. The diffuse uptake was demonstrated by bone scan in both malignant and benign effusions, with almost the same positive rate, i.e. 62% and 57%, respectively. Of 46 patients with the diffuse uptake, 32 (69.6 %) showed weak activity, 12 (26.1 %) showed moderate activity less than that of the rib and 2 (4.3%) showed strong activity equal to the rib uptake (Fig. 1). A definite difference between malignant and benign effusions was not noted in the intensity of uptake. 
The positive rate of uptake tended to be higher with the increase in effusion volume estimated from chest roentgenogram (Table 2). 
Of 36 patients with the uptake of 99mTc-MDP, 22 (61%) similarly showed intrathoracic, diffuse uptake of 67Ga (Table 3). Of 10 patients without the uptake of 99mTc-MDP, none showed uptake of 67Ga. 
DISCUSSION 
Diffuse increased radioactivity in the thoracic region occasionally has been observed in 99mTc phosphate bone studies, Non-osseous uptake by skeletal agents is a well-known fact and some investigators have reported diffuse intrathoracic accumulation of skeletal agents in several disease states such as metastatic calcification,8-10 pleural effusion,4-7 radiation pneumonitis,11 alveolar microlithiasis12 and fibrothorax.13 Levy and Park14 reported that unilateral thoracic soft-tissue accumulation of bone agents was present in 60 of 130 (46%) of patients with lung cancer. In that study, they emphasized that radiation therapy for lung tumors was the most significant of the factors studied in unilateral soft-tissue uptake of bone agents in the thorax of patients with lung cancer. But our patient population did not receive any radiotherapy. 
The precise mechanism of phosphate accumulation in effusion remains to be clarified, although some speculations as to its mechanism have been reported.4-7 Disruption or altered capillary permeability in the pleura is considered as the most likely mechanism in malignant effusion. With an inflammatory change or due to a hypervascular tumor in the pleura, increased vascularity could occur in that area. Metabolic effects exerted by tumor cells might increase the amount of calcium and phosphorus in effusion. Collagen formation and activated phosphatase in effusion might also be related to the localization of 99mTc-MDP.13 
In our study, 99mTc-MDP accumulation in pleural effusion was noted not only in patients with malignant effusion, but also with benign effusion, with almost the same positive rate. Especially there was a diffuse uptake of the radiotracer in all of 3 patients with effusion due to congestive heart failure, and also 2 patients with thoracotomy. These effusions are so-called transudates, not exudates. About 70 % of our subjects showed slight or vague accumulation of 99mTc-MDP in the hemithorax. The positive rate of accumulation had a tendency to be higher with the increase in intrathoracic effusion volume. Patients with a pleural effusion less than 300 ml did not show diffuse intrathoracic uptake on bone scan because up to 300 ml of fluid is not apparent in the usual upright chest X-ray (Table 2). These results probably suggest that a simple effusion is a principal factor in the diffuse intrathoracic accumulation of 99mTc-MDP. 
As to the comparison between 67Ga citrate and 99mTc-MDP, of 46 cases, 22 (47.8%) showed diffuse, slight accumulation of both agents, and 10 (21.7%) showed accumulation of neither 67Ga nor 99mTc-MDP. This correlation between 67Ga and 99mTc-MDP seems to suggest that 67Ga accumulation in effusion also might be partly due to simple diffusion into the intrapleural space. Hatfield15 published an article on gallium accumulation in the ipsilateral hemithorax as the effect of previous thoracic surgery, which seems to endorse our results. 
From these results, we suggest that, once 99mTc-MDP is distributed throughout the extracellular compartment, in the third space after i.v. injection, it passively transudes into the intrapleural space and is cleared slowly from the congested intrathoracic space. Transudates including 99mTc-MDP are those fluids which occur in response to an increase in hydrostatic pressures in the capillaries, a decrease in the oncocytotic pressure of plasma, a decrease in intrapleural pressure, or a combination of these factors. 
In conclusion, while it is difficult to define a single mechanism which accounts for all of the cases we studied, we are convinced that, in patients with malignant or benign pleural effusion, passive diffusion of 99mTc-MDP along with effusion and its slow clearance from the congested intrathoracic space play a major role in diffuse intrathoracic accumulation in bone scan. 
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