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Antibody Guided Targeting of Non-Small Cell Lung Cancer Using ¹¹¹In-labeled HMFG1 F(ab')₂ Fragments

Imperial Cancer Research Fund, Oncology Group [H. P. K., G. B. S., N. S. C-L., D. E. S., A. A. E.], Department of Clinical Oncology [H. P. K., N. S. C-L., D. E. S., G. R. H., C. G. M., A. A. E.], Respiratory Unit [R. W.], Medical Physics [G. R. H.], Diagnostic Radiology [A. A. E.], Royal Postgraduate Medical School, Hammersmith Hospital, London, W12 OHS, and Imperial Cancer Research Fund, London WC2A 3PX [J. J. T-P.], England

Immunoscintigraphy using F(ab')₂ fragments of tumor-associated monoclonal antibody HMFG1 was performed in 14 patients with primary and metastatic non-small cell carcinoma of lung cancer. The antibody was conjugated with diethylenetriamine pentaacetic acid and labeled with ¹¹¹In. Quality control studies showed efficient incorporation of ¹¹¹In onto antibody (5 mCi/mg), no significant loss of immunoreactivity, and in vitro and in vivo stability.

The optimal time for imaging was between 48 and 72 h. Following i.v. administration, serum activity fell rapidly (ta = 2.5 ± 1.3 (SD) h; tb = 42 ± 4.5 h). The majority of the radioactivity was associated with the plasma and not with the blood cells.

All patients had a significant concentration of ¹¹¹In in the liver (approximately 20% of the injected dose, 48 h postadministration). No toxicity was encountered. No human antimurine-IgG antibody was detected in any of the patients within 4 months of follow-up, even in patients receiving two administrations of F(ab')₂ fragments.

Localization of all primary lesions and the majority (80%) of metastatic lesions was achieved. Seven of 14 patients were also studied using a ¹¹¹In-labeled nonspecific antibody (Fab'₂ fragment (4C4). In three patients the specificity index was higher than the other four (P < 0.05).

We conclude that although successful targeting of ¹¹¹In-labeled (Fab')₂ fragments of HMFG1 can be achieved in patients with non-small cell carcinoma of lung, observable tumor localization can also be achieved using a nonspecific antibody. Based on these findings, we recommend that in order to demonstrate specific radioimmunolocalization, patients with lung and possibly other tumor types should be studied using both specific and nonspecific antibodies.

¹ To whom requests for reprints should be addressed, at Imperial Cancer Research Fund Oncology Group, Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, England.

Received 6/16/87. Revised 11/30/87. Accepted 12/10/87.

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