Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: results of a phase II study with 90Y-labeled biotin

Paganelli, Giovanni; Cicco, Concetta De; Ferrari, Mahila; Carbone, Giuseppe; Pagani, Gianmatteo; Leonardi, Maria Cristina; Cremonesi, Marta; Ferrari, Annamaria; Pacifici, Monica; Dia, A. Di; Santis, Rita De; Galimberti, Viviana; Luini, Alberto; Orecchia, Roberto; Zurrida, Stefano; Veronesi, Umberto

doi:10.1007/s00259-009-1260-4

Cited by 33 publications

(37 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This approach, already tested in breast cancer by our group, has been shown to be a safe procedure, delivering about 20 Gy to the tumor bed after a single i.v. injection of 3.7 GBq of 90 Y-biotin [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Eleven-Year Experience with the Avidin-Biotin Pretargeting System in Glioblastoma: Toxicity, Efficacy and Survival

Grana

Chinol

Cicco

et al. 2012

TONMEDJ

View full text Add to dashboard Cite

Background:The 3-step avidin-biotin pretargeting approach is applied in patients with recurrent glioblastoma (GBM), using biotinylated anti-tenascin monoclonal antibody as the first step of pretargeting followed by avidin and 90 Ybiotin.Methods: The present study reviews objective response and overall survival rates in 502 glioblastoma patients treated with 3-step radioimmunotherapy in our institute from December 1994 to December 2005. Patients underwent standard treatment before receiving Pretargeted Antibody-Guided Radionuclide Therapy with 90 Y-biotin (PAGRIT ® ).Results: Of the 502 patients, 272 (54%) were evaluable for response and 375 (75%) for overall survival. 174 patients (64%) continued to progress after PAGRIT ® , 77 (28%) obtained disease stabilization, and 21 (8%) showed objective tumor regression. Survival of the 375 evaluable patients was 98.4% at 6 months, 79.2% at 12 months, 51.7% at 18 months, and 30.7% at 24 months after the first cycle of PAGRIT ® . All 375 received 3-step PAGRIT ® at recurrence of GBM. The median survival time from diagnosis was 19 months. Conclusion:The results from this retrospective analysis suggest that 90 Y-biotin PAGRIT ® interferes with the progression of glioblastoma, prolonging survival in a larger number of patients. Our analysis forms the basis for further prospective trials, where radioimmunotherapy, which is known to be more effective in minimal residual disease, could be offered immediately after surgery.

show abstract

Section: Discussionmentioning

confidence: 99%

Eleven-Year Experience with the Avidin-Biotin Pretargeting System in Glioblastoma: Toxicity, Efficacy and Survival

Grana

Chinol

Cicco

et al. 2012

TONMEDJ

View full text Add to dashboard Cite

show abstract

“…Benefits of APBI include the precise treatment of a limited volume with increased irradiation dose-to-target area, decreased time course of treatment, and less toxicity. A wide range of APBI techniques have been reported, including (1) external beam conformal irradiation [14, 15], (2) intraoperative irradiation using soft x-rays supplied by a portable spherical device [10, 16] or accelerator produced electron beam [17, 18], (3) MammoSite RTS brachytherapy using an iridium-192 ( 192 Ir) source containing balloon catheter device [19, 20], and (4) other brachytherapy techniques using interstitial implants [21–25] or targeted radiotherapeutic agents [26]. However, APBI techniques may be limited by instrument availability.…”

Section: Introductionmentioning

confidence: 99%

Post-lumpectomy intracavitary retention and lymph node targeting of 99mTc-encapsulated liposomes in nude rats with breast cancer xenograft

Goins

Phillips

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

Liposomes are recognized drug delivery systems with tumor-targeting capability. In addition, therapeutic or diagnostic radionuclides can be efficiently loaded into liposomes. This study investigated the feasibility of utilizing radiotherapeutic liposomes as a new post-lumpectomy radiotherapy for early-stage breast cancer by determining the locoregional retention and systemic distribution of liposomes radiolabeled with technetium-99m (99mTc) in an orthotopic MDA-MB-231 breast cancer xenograft nude rat model. To test this new brachytherapy approach, a positive surgical margin lumpectomy model was set up by surgically removing the xenograft and deliberately leaving a small tumor remnant in the surgical cavity. Neutral, anionic, and cationic surface-charged fluorescent liposomes of 100 and 400 nm diameter were manufactured and labeled with 99mTc-BMEDA. Locoregional retention and systemic distribution of 99mTc-liposomes injected into the post-lumpectomy cavity were determined using non-invasive nuclear imaging, ex vivo tissue gamma counting and fluorescent stereomicroscopic imaging. The results indicated that 99mTc-liposomes were effectively retained in the surgical cavity (average retention was 55.7 ± 24.2% of injected dose for all rats at 44 h post-injection) and also accumulated in the tumor remnant (66.9 ± 100.4%/g for all rats). The majority of cleared 99mTc was metabolized quickly and excreted into feces and urine, exerting low radiation burden on vital organs. In certain animals 99mTc-liposomes significantly accumulated in the peripheral lymph nodes, especially 100 nm liposomes with anionic surface charge. The results suggest that post-lumpectomy intracavitary administration of therapeutic radionuclides delivered by 100-nm anionic liposome carrier is a potential therapy for the simultaneous treatment of the surgical cavity and the draining lymph nodes of early-stage breast cancer.

show abstract

“…1a and as expected from bibliographic data (43), binding of avidin but not streptavidin to a panel of tumor as well as normal cells was confirmed by FACS analysis. Therefore, to evaluate their diffusion kinetics from a treated tissue, either 125 I-radiolabeled avidin or streptavidin was injected in the muscle of one hind limb of each mouse, simulating the recently described approach of cancer pretargeted radiotherapy named IART (37)(38)(39), and at different time points the mice were sacrificed, and the treated and controlateral limb (muscle), blood, liver, and kidney were collected, and radioactivity was measured by a ␥ counter. Previously published data from our group showed that the residence time of 125 I-labeled avidin and streptavidin in the treated tissue is very short, with ϳ8% of the injected dose/100 mg observed after 1 h and less than 1% ID/100 mg after 24 h. In agreement to previous pharmacokinetics data on avidin and streptavidin intravenously injected, the avidin diffused from the injected tissue, exhibited a faster clearance from the blood than streptavidin, and accumulated in the liver and kidney, whereas streptavidin preferentially accumulated in the kidney (35).…”

Section: Cell Binding and Tissue Kinetics Of Avidin And Streptavidin-mentioning

confidence: 99%

“…The use of native avidin, injected during surgery in the tissue surrounding an excised breast tumor, followed by intravenous radioactive biotin within the next 24 h, has been recently applied in the clinic to prevent local tumor recurrences. This method, named intraoperative avidination for radionuclide treatment (IART) (37)(38)(39), is an innovative way to perform pretargeted tissue radiotherapy, but it is conditioned by the short tissue half-life of native avidin that, diffusing from the injected breast into liver and kidney, requires the blocking of the radioactive biotin uptake in these organs that is performed by injecting human biotinylated albumin (HSAbiot) 10 min before radioactive biotin. The present data confirm that OXavidin HABA , being stable in injected tissues, could be a valid alternative to native avidin in IART.…”

mentioning

confidence: 99%

Biochemical and Biological Characterization of a New Oxidized Avidin with Enhanced Tissue Binding Properties

Verdoliva¹,

Bellofiore²,

Rivieccio³

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Chicken avidin and bacterial streptavidin are widely employed in vitro for their capacity to bind biotin, but their pharmacokinetics and immunological properties are not always optimal, thereby limiting their use in medical treatments. Here we investigate the biochemical and biological properties of a new modified avidin, obtained by ligand-assisted sodium periodate oxidation of avidin. This method allows protection of biotin-binding sites of avidin from inactivation caused by the oxidation step and delay of avidin clearance from injected tissue by generation of aldehyde groups from avidin carbohydrate moieties. Oxidized avidin shows spectroscopic properties similar to that of native avidin, indicating that tryptophan residues are spared from oxidation damage. In strict agreement with these results, circular dichroism and isothermal titration calorimetry analyses confirm that the ligand-assisted oxidation preserves the avidin protein structure and its biotin binding capacity. In vitro cell binding and in vivo tissue residence experiments demonstrate that aldehyde groups provide oxidized avidin the property to bind cellular and interstitial protein amino groups through Schiff's base formation, resulting in a tissue half-life of 2 weeks, compared with 2 h of native avidin. In addition, the efficient uptake of the intravenously injected 111 In-Biotin-DOTA (ST2210) in the site previously treated with modified avidin underlines that tissue-bound oxidized avidin retains its biotin binding capacity in vivo. The results presented here indicate that oxidized avidin could be employed to create a stable artificial receptor in diseased tissues for the targeting of biotinylated therapeutics.

show abstract

Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: results of a phase II study with 90Y-labeled biotin

Abstract: IART plus reduced EBRT can accelerate irradiation after conservative breast surgery.

Cited by 33 publications

References 29 publications

Eleven-Year Experience with the Avidin-Biotin Pretargeting System in Glioblastoma: Toxicity, Efficacy and Survival

Eleven-Year Experience with the Avidin-Biotin Pretargeting System in Glioblastoma: Toxicity, Efficacy and Survival

Post-lumpectomy intracavitary retention and lymph node targeting of 99mTc-encapsulated liposomes in nude rats with breast cancer xenograft

Biochemical and Biological Characterization of a New Oxidized Avidin with Enhanced Tissue Binding Properties

Contact Info

Product

Resources

About