Intraoperative avidination for radionuclide therapy: a prospective new development to accelerate radiotherapy in breast cancer.

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 (approximately 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.

IART: intraoperative avidination for radionuclide treatment. A new way of partial breast irradiation.

A new procedure, known as Intraoperative Avidination for Radionuclide Therapy (IART), is described in breast cancer patients. In this paper, we provide proof of the principle that intraoperative injection of avidin in the tumour bed after quadrantectomy allows homing in of intravenously (IV) administered radioactive biotin to the target site. This approach of targeted therapy consists of two steps: (i) "avidination" of the anatomical area of the tumour with avidin injected by the surgeon, into and around the tumour bed; (ii) targeting the anatomical area of the tumour by IV injection of radiolabelled biotin. The scintigraphic images demonstrated fast and stable uptake of labelled biotin at the site of operated breast. The radiation dose released to the index quadrant was more than 5 Gy/GBq, consistent with a boost of 20 Gy for an activity of 3.7 GBq 90Y-biotin (100mCi). A further large clinical trial facing IART in combination with reduced external-beam radiotherapy is, in our opinion, fully justified.

Dosimetric model for locoregional treatments of brain tumors with 90Y-conjugates: clinical application with 90Y-DOTATOC.

UNLABELLED: Locoregional (LR) administration of (90)Y-conjugates after surgical debulking is a promising therapeutic option of gliomas. Dosimetry is highly recommended, as patient-specific parameters influence the absorbed dose to target and normal tissues. After tumor resection, the absorbed dose must be carefully evaluated in the rim of tissue surrounding the resected area. The aim of this study was to calculate and provide the S values, according to the MIRD concept, for dosimetry of LR brain treatments with several (90)Y-labeled compounds. The S values thus obtained have been clinically applied in 12 patients treated with (90)Y-labeled [DOTA(0),D-Phe(1),Tyr(3)]octreotide ((90)Y-DOTATOC). METHODS: An anthropomorphic model for Monte Carlo simulations was developed to evaluate absorbed doses in brain-adjacent tissue (BAT) and in normal brain. To adapt the model to single patients, S values were evaluated taking into account (i) different surgical resection cavity (SRC) volumes, (ii) different percentages of conjugate binding to the cavity wall, and (iii) different depths of percolation of the conjugate trough the cavity wall. BAT was divided into 1-mm-thick consecutive adjacent shells to evaluate the dose distribution around the cavity. Corresponding S values were obtained to allow dosimetric evaluation in brain LR therapy with (90)Y-conjugates. In the clinical treatments, 0.4-1.1 GBq of (90)Y-DOTATOC were injected into the SRC via an appropriate catheter. The activity in the SRC was assumed to be the difference between the total injected activity and the activity in the blood plus the activity cumulatively eliminated with the urine. RESULTS: Assuming no diffusion, with a mean residence time in SRC of 60 +/- 8 h, absorbed doses to shell II were 0.25 and 0.03 Gy/MBq for SRC volumes of 7.2 and 65.4 mL, respectively. Assuming a slight diffusion of 1 mm with a 7.2-mL SRC, absorbed dose to shells I, II, and VI were consistently different: 5.32, 2.53, and 0.12 Gy/MBq, respectively. Mean doses to normal brain, red marrow, bladder wall, and total body were 0.015, 0.03, 1.22, and 0.006 MGy/MBq. CONCLUSION: The model proved to be suitable for the dosimetry of several LR therapies with (90)Y-conjugates. According to our results, LR treatment with (90)Y-DOTATOC can safely deliver very high doses to target tissue, sparing normal organs including brain.