Evaluation of a new biotin-DOTA conjugate for pretargeted antibody-guided radioimmunotherapy (PAGRIT®)

Urbano, Nicoletta; Papi, Stefano; Ginanneschi, Mauro; Santis, Rita De; Pace, Silvia; Lindstedt, Ragnar; Ferrari, Liliana; Choi, Sang-Jin; Paganelli, Giovanni; Chinol, Marco

doi:10.1007/s00259-006-0124-4

Cited by 41 publications

(34 citation statements)

References 29 publications

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“…Advantages of the avidin/biotin based systems include; the high affinity between avidin and biotin leads to efficient capture of the radionuclide by antibody [125,126] and a correspondingly high tumor to normal tissue ratio that can be achieved. Mean tumor to marrow absorbed dose ratios of 63:1 have been published with this method, which compares well to a ratio of 6:1 with conventional RIT [127].…”

Section: Pre-targeting Approachesmentioning

confidence: 99%

Imaging in targeted delivery of therapy to cancer

2009

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We review the current status of imaging as applied to targeted therapy with particular focus on antibody-based therapeutics. Antibodies have high tumor specificity and can be engineered to optimize delivery to, and retention within, the tumor. Whole antibodies can activate natural immune effector mechanisms and can be conjugated to beta- and alpha-emitting radionuclides, toxins, enzymes, and nanoparticles for enhanced therapeutic effect. Imaging is central to the development of these agents and is used for patient selection, performing dosimetry and assessment of response. gamma- and positron-emitting radionuclides may be used to image the distribution of antibody-targeted therapeutics While some radionuclides such as iodine-131 emit both beta and gamma radiation and are therefore suitable for both imaging and therapy, others are more suited to imaging or therapy alone. Hence for radionuclide therapy of neuroendocrine tumors, patients can be selected for therapy on the basis of gamma-emitting indium-111-octreotide imaging and treated with beta-emitting yttrium-90-octreotate. Positron-emitting radionuclides can give greater sensitivity that gamma-emitters but only a single radionuclide can be imaged at one time and the range of radionuclides is more limited. The multiple options for antibody-based therapeutic molecules, imaging technologies and therapeutic scenarios mean that very large amounts of diverse data are being acquired. This can be most effectively shared and progress accelerated by use of common data standards for imaging, biological, and clinical data.

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Section: Pre-targeting Approachesmentioning

confidence: 99%

Imaging in targeted delivery of therapy to cancer

2009

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“…Anhydrous sodium acetate (NaAc), acetic acid, and diethylenetriaminepentaacetic acid were purchased from Sigma-Aldrich Italy at the highest available purity. A NaAc buffer at 1 mol/L (pH 5.0) was prepared using MilliQ water (q = 18 MV/cm) as previously described (12). Indium-111 chloride ( …”

Section: Methodsmentioning

confidence: 99%

“…The radiolabeling of DOTA-biotin was carried out following a previously described procedure (12). Briefly, a volume of NaAc buffer, equal to that of the radionuclide MCl 3 (M =…”

Section: Radiolabelingmentioning

confidence: 99%

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

Paganelli¹,

Ferrari²,

Ravasi³

et al. 2007

Clinical Cancer Research

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“…32, [52][53][54][55] Theoretically, the biotin moiety could be conjugated to the antibody or carry the radionuclides, and both approaches have been evaluated for PRIT. 32 Theoretical modeling suggests that the combination of (strept)avidin-conjugated targeting vehicles and biotin-labeled effectors offers pharmacokinetic advantages over biotin-conjugated targeting vehicles with (strept)avidin-labeled effectors in the absence of antigen internalization.…”

mentioning

confidence: 99%

Pretargeted Radioimmunotherapy for Hematologic and Other Malignancies

Walter

Press

Pagel

2010

Cancer Biotherapy and Radiopharmaceuticals

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SummationRadioimmunotherapy (RIT) has emerged as one of the most promising treatment options, particularly for hematologic malignancies. However, this approach has generally been limited by a suboptimal therapeutic index (target-to-nontarget ratio) and an inability to deliver sufficient radiation doses to tumors selectively. Pretargeted RIT (PRIT) circumvents these limitations by separating the targeting vehicle from the subsequently administered therapeutic radioisotope, which binds to the tumor-localized antibody or is quickly excreted if unbound. A growing number of preclinical proof-of-principle studies demonstrate that PRIT is feasible and safe and provides improved directed radionuclide delivery to malignant cells compared with conventional RIT while sparing normal cells from nonspecific radiotoxicity. Early phase clinical studies corroborate these preclinical findings and suggest better efficacy and lesser toxicities in patients with hematologic and other malignancies. With continued research, PRIT-based treatment strategies promise to become cornerstones to improved outcomes for cancer patients despite their complexities.

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Evaluation of a new biotin-DOTA conjugate for pretargeted antibody-guided radioimmunotherapy (PAGRIT®)

Abstract: These results indicate that the new biotin-DOTA conjugate may be a suitable candidate for pretargeting trials.

Cited by 41 publications

References 29 publications

Imaging in targeted delivery of therapy to cancer

Imaging in targeted delivery of therapy to cancer

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

Pretargeted Radioimmunotherapy for Hematologic and Other Malignancies

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