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Intraoperative Avidination for Radionuclide Therapy: A Prospective New Development to Accelerate Radiotherapy in Breast Cancer

Authors' Affiliations: Divisions of ¹ Nuclear Medicine, ² Medical Physics, and ³ Senology, European Institute of Oncology; ⁴ European Institute of Oncology, Milan, Italy; ⁵ Department of Pharmacy, Pharmacokinetics Laboratory, University of Patras, Patras, Greece; and ⁶ R&D, Sigma-Tau SpA, Rome, Italy

Requests for reprints: Giovanni Paganelli, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. Phone: 39-025-748-9043; Fax: 39-025-748-9040; E-mail: divisione.medicinanucleare{at}ieo.it.

Purpose: In a continuous effort to seek for anticancer treatments with minimal side effects, we aim at proving the feasibility of the Intraoperative Avidination for Radionuclide Therapy, a new procedure for partial breast irradiation.

Experimental Design: To assess doses of ⁹⁰Y-DOTA-biotin to target (i.e., breast tumor bed) and nontarget organs, we did simulation studies with ¹¹¹In-DOTA-biotin in 10 candidates for conservative breast surgery. Immediately after quadrantectomy, patients were injected with 100-mg avidin in the tumor bed. On the following day, patients were given ¹¹¹In-DOTA-biotin (111 MBq) i.v. after appropriate chase of biotinylated albumin (20 mg) to remove circulating avidin. Biokinetic studies were done by measuring radioactivity in scheduled blood samples, 48-h urine collection, and through scintigraphic images. The medical internal radiation dose formalism (OLINDA code) enabled dosimetry assessment in target and nontarget organs.

Results: Images showed early and long-lasting radioactive biotin uptake in the operated breast. Rapid blood clearance (<1% at 12 h) and urine excretion (>75% at 24 h) were observed. Absorbed doses, expressed as mean ± SD in Gy/GBq, were as low as 0.15 ± 0.05 in lungs, 0.10 ± 0.02 in heart, 0.06 ± 0.02 in red marrow, 1.30 ± 0.50 in kidneys, 1.50 ± 0.30 in urinary bladder, and 0.06 ± 0.02 in total body, whereas in the targeted area, they increased to 5.5 ± 1.1 Gy/GBq (50% ISOROI) and 4.8 ± 1.0 Gy/GBq (30% ISOROI).

Conclusion: Our preliminary results suggest that Intraoperative Avidination for Radionuclide Therapy is a simple and feasible procedure that may improve breast cancer patients' postsurgical management by shortening radiotherapy duration.