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Antibody guided targeting of non-small cell lung cancer using 111In-labeled HMFG1 F(ab')2 fragments
H P Kalofonos1, G B Sivolapenko, N S Courtenay-Luck
1Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
Abstract:
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 (t1/2a = 2.5 +/- 1.3 (SD) h; t1/2b = 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 less than 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.
Insights
Radioimmunoscintigraphy using indium-111-labeled antibody fragments successfully targeted non-small cell lung cancer. However, nonspecific antibody fragments also showed tumor localization, necessitating the use of both specific and nonspecific antibodies for accurate diagnosis.
Area of Science:
- Oncology
- Nuclear Medicine
- Immunology
Background:
- Non-small cell lung cancer (NSCLC) diagnosis and staging require accurate imaging techniques.
- Radioimmunoscintigraphy offers potential for targeted tumor visualization using radiolabeled antibodies.
Purpose of the Study:
- To evaluate the efficacy and specificity of immunoscintigraphy with indium-111-labeled F(ab')2 fragments of the HMFG1 monoclonal antibody in patients with NSCLC.
- To compare tumor localization using a specific antibody (HMFG1) versus a nonspecific antibody (4C4).
Main Methods:
- 14 patients with NSCLC underwent immunoscintigraphy using 111In-labeled HMFG1 F(ab')2 fragments.
- Quality control assessed radiolabeling efficiency, immunoreactivity, and stability.
- Pharmacokinetics and biodistribution were analyzed.
- Seven patients were also studied with 111In-labeled nonspecific 4C4 F(ab')2 fragments.
Main Results:
- The 111In-labeled HMFG1 F(ab')2 fragments demonstrated successful targeting of primary and metastatic NSCLC lesions (80% of metastases).
- Optimal imaging occurred between 48-72 hours post-injection.
- Significant liver uptake (approx. 20%) was observed; no toxicity or human antimurine-IgG antibodies were detected.
- Tumor localization was also observed with the nonspecific 4C4 antibody, with a higher specificity index in 3/7 patients.
Conclusions:
- 111In-labeled HMFG1 F(ab')2 fragments can target NSCLC, but nonspecific antibodies also show tumor localization.
- To confirm specific radioimmunolocalization, studies should include both specific and nonspecific antibodies for lung and potentially other cancers.