Pilot therapy trial of CEA positive tumours using a three-step pretargeting approach

G. Paganelli, P. Magnani, M. Chinol, F. Sudati, F. Zito, F. Mangili, M. Li, C. F. Meares, A. G. Siccardi, F. Fazio

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The three-step pretargeting approach, based on the avidin-biotin system, has been shown to improve the target/non target ratio in radioimmunoscintigraphy. This pilot study was designed to assess the feasibility of applying the same strategy to radioimmunotherapy. Five patients, with advanced metastatic CEA positive carcinomas were studied. All patients received two cycles of therapy with an interval of 3 months in between. The protocol consisted of an i.v. injection of 10 mg of biotinylated anti-CEA antibody, followed 24h later by avidin: 3 mg as rapid bolus (chase effect) plus 50 mg in 100 ml of saline. Biotin-LC-DOTA (2.5 mg) was labelled with Y-90 and injected i.v. 24 h later. The injected dose ranged between 1.7 and 1.85 GBq for the first cycle and 3.7 GBq for the second treatment. No acute or delayed side effects were observed. Haematologic toxicity was negligible with a transient decrease of RBC, WBC and PTL in the first 8-15 days after each cycle of therapy. Two patients developed a weak HAMA response after the second treatment and three showed a moderate anti-avidin immunoresponse. The plasma clearance of 90Y-DOTA-LC-biotin showed a bi- exponential curve with a t(1/2) of 106 ± 3 min and 20.5 ± 1.5 h respectively. The estimated absorbed dose to bone marrow was 42 cGy and 104 cGy for the first and second cycle respectively. Two out of five patients evaluated showed a minor benefit. In particular, one patient with disseminated liver metastases had a stable disease after the second cycle of therapy lasting over 1 year of follow-up. The data from this study indicate that high doses of 90Y-biotin can be administered safely without bone marrow toxicity. Further improvements, however, are necessary to enhance the efficacy of this approach for cancer therapy.

Original languageEnglish
Pages (from-to)96-104
Number of pages9
JournalTumor Targeting
Issue number2
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology


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