Endobronchial Deposition of Radioactive Monoclonal Antibody in Patients with Inoperable Non-Small-Cell Carcinoma of the Lung

Endobronchial Deposition of Radioactive Monoclonal Antibody in Patients with Inoperable Non-Small-Cell Carcinoma of the Lung

the cases turned out to he nontuherculous benign pleuritis. Therefore, we did not include those cases that had heen diagnosed as tuberculous pleuritis...

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the cases turned out to he nontuherculous benign pleuritis. Therefore, we did not include those cases that had heen diagnosed as tuberculous pleuritis on the hasis of the diagnostic therapeutic trial. \Ve are now conducting a prospective study to evaluate more objectively the significance of subpleural inflammatory infiltrate. We have so far found eight cases with this finding in the pleural biopsy specimen; none of the patients has tuherculous pleuritis.

Nobuhiko Nagata, M .D . . Division of Respiratory Disease, University of Occupational and Enoironmental Health, Kitakyushu, Japan Reprint requests: Dr. Nagata, Div~\1(1n of Respiratory Disease, Unioersitu of Occupational and Environmental Health, 1-1 lseigaoka , Yahatanishi-ku, Kitakyushu 807, Japan

The diagnosis of a coronary artery fistula , usually based on clinical and angiographic findings, has recently been increasingly reported with the use of noninvasive modalities, including twodimensional and Doppler echocardiography, Doppler color-flow imaging, contrast echocurdiographv, and contrast material-enhanced cine computed tomography. One potential limitation of these techniques is in the evaluation of small shunts! Biplane transesophageal echocardiography offers the advantage of a high degree of resolution, the ability to image the lesion in cross-sectional and longitudinal planes, and the added advantage of color-How Doppler imaging, which may he useful for detecting shunts. We believe that transesophageal echocardiography will be used in the evaluation of coronary artery fistulae with increasing frequency and success in the future .

Allen J. 111ylor; M.D., Kevin M . Rogan , M.D ., Neal S. Gaither; M .D., Robert W Hull, M .D ., and Fred H. Edwards, M .D ., F.C.C .P., Walter Reed Anny Medical Center; Washington, DC

Traumatic Coronary ArteryAtrioventricular Fistula A 26-Year Follow-up with Application of Transesophageal Echocardiography

REFERENCES To the Editor: Our institution described the first surgical repair of a traumatic coronary artery fistula in 1965.' \Ve recently evaluated this lesion with transesophageal echocardiography, In 1964, an 18-year-old soldier was accidentally wounded in the chest with a .38 caliber pistol, resulting in a cardiac laceration. Several weeks after the initial repair, he was referred to our institution fill the evaluation of dyspnea and a continuous murmur. A fistula from the right coronary artery to the right atrium and ventricle was diagnosed and then repaired hy means of prnximal and distal ligation of the right coronary artery. lie did well until 1986, when atypical chest pain developed. The cardiac catheterization findings were normal except for a calcified, aneurysmal right coronary artery, which ended blindly Recently, we evaluated this lesion with biplane transesophageal echocardiography The dilated right coronary artery was visualized in both the horizontal and longitudinal planes. Utilizing Doppler color-flow imaging, we found no evidence of communication to either the right atrium or the right ventricle (Fig 1).

Jones RC, Jahnke EJ. Coronary artery-atrioventricular fistula and ventricular septal defect due to penetrating wound of the heart. Circulation 1965; 32:995-1000 2 Miyatake K, Okamoto M, Kinoshita N, Fusejima K, Sakakibara H, Nimura Y. Doppler echocardiographic features of coronary arteriovenous fistula : complementary roles of cross sectional echocardiography and the Doppler technique . Br Heart J 1984; 51:508-18

Endobronchial Deposition of Radioactive Monoclonal Antibody in Patients with Inoperable Non-Small-Cell Carcinoma of the Lung To the Editor: We read with great interest the article by Stein and Goldenberg.' which appeared in the June 1991 issue of Chest. They reviewed

FIGURE 1. Transesophageal echocardiogram demonstrates the course of the enlarged right coronary artery (arrowheads). Ao = aorta; RA = right atrium; RV = right ventricle. Left panel, Horizontal-plane image shows dilated proximal right coronary artery adjacent to the right sinus of Valsalva. Right panel, Longitudinalplane image shows dilated right coronary artery traversing atrioventricular groove.

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Communications to the Editor

development techniques and applications for monoclonal antibodies (MoAbs) in the diagnosis, therapy, and study of lung cancer. They also described some of the limitations encountered in the in vivo use of radiolabeled MoAbs. We agree with them that the successful clinical application of radiolabeled MoAbs requires the selective localization of the radioantibody at the tumor site and the achievement of a high tumor-to-background ratio . Unfortunately, tumor accretion of radiolabeled MoAbs is usually low, which appears to be a considerable limitation to the clinical use of radiolabeled MoAhs. Furthermore, when given intravenously, radiolabeled MoAbs produce some undesirable activity in certain organs, such as the liver, spleen, and bone marrow. This nonspecillc uptake can be critical in therapeutic trials with radiolabeled MoAbs. In a recent study' we tried to overcome these limitations using endobronchial administration of radiolabeled MoAbs in patients with non-small-cell lung cancer, We tested the feasibility of endobronchial direct delivery of radiolabeled MoAbs and the biodistribution of the radiotracer 11I1-B72.3; a pancarcinoma MoAb that reacts with adenocarcinoma and adenosquamous lung cancer cells was placed on the tumor protruding into the bronchial lumen under visual monitoring, using a catheter during llberoptic bronchoscopy. A nonspecillc anti-hepatitis B virus antibody was used as the negative control. We demonstrated that radiolabeled MoAbs can be administered through a bronchoscope without side effects or adverse reactions. Furthermore, analysis of serial imaging data showed that radiolabeled MoAb was specifically retained at the tumor site for up to six days. No other organ was visualized with the exception of faint activity in the gastrointestinal tract, bladder, and thyroid gland (Fig 1). The activity removed from the bronchi by ciliary action was in fact swallowed, digested , and partially absorbed. The ciliary epithelium of the bronchi, however, proved to be an effective barrier to molecules with a high molecular weight, such as MoAb molecules. In conclusion, we have found that endobronchial administration of radio labeled MoAhs is a feasible technique and leads to very efficient targeting of lung tumors. It would be of interest to know whether the authors consider this approach suitable for therapeutic trials with radiolabeled MoAhs. Matteo Sofia, M.D. , Silvana Del ~cchlo, M.D., Antonella Petrillo, M.D ., Mauro Mormile, M.D., Marco Salvatore , M.D ., and Luigi Carratu, M.D ., F.C.C .P., University of Naples, Naples, Italy Reprint requests: Dr. Sofia, Clinka Pneumologica II Mculta , Ospedale Monaldi, Vaa L . Bianchi, 80131 Naples, Italy REFERENCES Stein R, Goldenberg D M. Prospects for the management of nonsmall-cell carcinoma of the lung with monoclonal antibodies. Chest 1991 ; 99 :1466-76 2 Del Vecchio S, Mansi L, Petrillo A, Camera L, Solla M, Marra A, et al. Intrabronchial administration of 13II-B72.3 monoclonal antibody in patients with lung cancer. Eur J Nucl Med 1991; 18:129-32 1b the Editor: Weappreciate the comments ofSolla and colleagues, and generally concur with their view that locoregional application of antibodies may provide advantages in tumor targeting and accretion. Indeed, intraperitoneal, intrapleural, and intrathecal administrations of radiolabeled antibodies have been reported.I.' With regard to

FIGURE I. Anterior views of whole body scans performed 2 h (len) and six days (right) after endobronchial deposition of radioactive monoclonal antibody (MoAb) in two patients with non-small-cell lung cancer. 1bp left, Early scan after deposition of specillc MoAb 13II-B72.3 shows retention of radioactivity at tumor site . 1bp right, Later scan in the same patient shows retention of radioactivity at the tumor site and the presence of thyroid activity. Bottom left , Early scan after deposition of nonspecillc (control) MoAh IJ'I_4C4 in another patient shows large amount of radioactivity in the left main bronchus, trachea, and gastrointestinal tract. Bottom right, Later scan shows that the nonspecillc antibody is not retained at the tumor site, and activity is present only in the thyroid gland. (Reprinted with permission from reference 2.)

endobronchial administration for radioimmunotherapy of cancer, this is in principle feasible . However, caution in the use of deeppenetrating beta-emitters should be exercised, since these may be toxic to adjacent normal tissues, particularly the lung . It will also be important to select an antibody that has a high discrimination between neoplastic and normal lung, and in this regard the B72.3 antibody may not be the best choice. CHEST I 102 I 5 I NOVEMBER, 1992

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