In vivo evaluation of a lead-labeled monoclonal antibody using the DOTA ligand

Milenic, Diane E.; Roselli, Mario; Brechbiel, Martin W.; Pippin, C. G.; McMurray, Thomas J.; Carrasquillo, Jorge A.; Colcher, David; Lambrecht, Richard M.; Gansow, Otto A.; Schlom, Jeffrey

doi:10.1007/s002590050246

Cited by 19 publications

(10 citation statements)

References 17 publications

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“…Clinically, IFN-α is well documented to enhance the expression of CEA and MHC antigens on freshly isolated human adenocarcinomas (40) and improve monoclonal antibody-targeting of carcinoma lesions following systemic administration in patients (45, 46). In patients with CEA-expressing carcinomas, therefore, we would expect the full repertoire of immunomodulatory properties of IFN-α to improve the clinical efficacy of our vaccine strategy.…”

Section: Discussionmentioning

confidence: 99%

The Antitumor and Immunoadjuvant Effects of IFN-α in Combination with Recombinant Poxvirus Vaccines

Hance

Rogers

Zaharoff

et al. 2009

Clinical Cancer Research

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Purpose: IFN-a is a pleiotropic cytokine possessing immunomodulatory properties that may improve the efficacy of therapeutic cancer vaccines.The aim of this study was to evaluate the effectiveness and compatibility of combining recombinant IFN-a with poxvirus vaccines targeting the human carcinoembryonic antigen (CEA) in murine models of colorectal and pancreatic adenocarcinomas, where CEA is a self-antigen. Experimental Design: The phenotypic and functional effects of IFN-a were evaluated in the draining inguinal lymph nodes of tumor-free mice. We studied the effect of the site of IFN-a administration (local versus distal) on antigen-specific immune responses to poxvirus vaccination. Mechanistic studies were conducted to assess the efficacy of IFN-a and CEA-directed poxvirus vaccines in tumor-bearing CEA transgenic mice. Results:We identified a dose and schedule of IFN-a that induced a locoregional expansion of the draining inguinal lymph nodes and improved cellular cytotoxicity (natural killer and CD8 + ) and antigen presentation. Suppression of the vaccinia virus was avoided by administering IFN-a distal to the site of vaccination. The combination of IFN-a and vaccine inhibited tumor growth, improved survival, and elicited CEA-specific CTL responses in mice with CEA + adenocarcinomas. In mice with pancreatic tumors, IFN-a slowed tumor growth, induced CTL activity, and increased CD8 + tumor-infiltrating lymphocytes. Conclusions: These data suggest that IFN-a can be used as a biological response modifier with antigen-directed poxvirus vaccines to yield significant therapeutic antitumor immune responses. This study provides the rationale and mechanistic insights to support a clinical trial of this immunotherapeutic strategy in patients with CEA-expressing carcinomas.

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Section: Discussionmentioning

confidence: 99%

The Antitumor and Immunoadjuvant Effects of IFN-α in Combination with Recombinant Poxvirus Vaccines

Hance

Rogers

Zaharoff

et al. 2009

Clinical Cancer Research

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“…203 Pb and 212 Pb are 2 isotopes with diagnostic and therapeutic properties (11,12). The favorable decay and imaging properties of 203 Pb make it an ideal matched-pair radioisotope for 212 Pb for targeted radionuclide therapy (11,12). 203 Pb is a manageable radioisotope with respect to dose preparation and waste disposal because of its half-life of 51.9 h. 203 Pb displayed a spatial resolution (1.6 mm) comparable to that of 99m Tc (Fig.…”

Section: Tablementioning

confidence: 97%

“…The treatment of 7.4 MBq of 212 Pb-DOTA-Re(Arg 11 )CCMSH cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study and highlighted its potential as a novel agent for targeted radionuclide therapy of melanoma. 203 Pb and 212 Pb are 2 isotopes with diagnostic and therapeutic properties (11,12). The favorable decay and imaging properties of 203 Pb make it an ideal matched-pair radioisotope for 212 Pb for targeted radionuclide therapy (11,12).…”

Section: Tablementioning

confidence: 99%

²⁰³Pb-Labeled α-Melanocyte–Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

Miao¹,

Figueroa²,

Fisher³

et al. 2008

J Nucl Med

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Peptide-targeted a-therapy with 7.4 MBq of 212 Pb-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ReO-[Cys 3,4,10 , D-Phe 7 ,Arg 11 ]a-MSH 3-13 ( 212 Pb-DOTA-Re(Arg 11 )CCMSH) cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patientspecific dosimetry and to monitor the tumor response to 212 Pb-DOTA-Re(Arg 11 )CCMSH therapy. The purpose of this study was to evaluate the potential of 203 Pb-DOTA-Re(Arg 11 )CCMSH as a matched-pair SPECT agent for 212 Pb-DOTA-Re(Arg 11 ) CCMSH. Methods: DOTA-Re(Arg 11 )CCMSH was labeled with 203 Pb in 0.5 M NH 4 OAc buffer at pH 5.4. The internalization and efflux of 203 Pb-DOTA-Re(Arg 11 )CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of 203 Pb-DOTARe(Arg 11 )CCMSH was examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT study was performed with 203 Pb-DOTA-Re(Arg 11 )CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h after injection. Results: 203 Pb-DOTARe(Arg 11 )CCMSH was easily prepared in NH 4 OAc buffer and completely separated from the excess nonradiolabeled peptide by reversed-phase high-performance liquid chromatography (RP-HPLC). 203 Pb-DOTA-Re(Arg 11 )CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of 203 Pb-DOTA-Re(Arg 11 )CCMSH activity internalized after a 20-min incubation at 25°C. After incubation of the cells in culture medium for 20 min, 78% of internalized activity remained in the cells. 203 Pb-DOTA-Re(Arg 11 )CCMSH exhibited a biodistribution pattern similar to that of 212 Pb-DOTA-Re(Arg 11 )CCMSH in B16/ F1 melanoma-bearing mice. 203 Pb-DOTA-Re(Arg 11 )CCMSH exhibited a peak tumor uptake of 12.00 6 3.20 percentage injected dose per gram (%ID/g) at 1 h after injection. The tumor uptake gradually decreased to 3.43 6 1.12 %ID/g at 48 h after injection. 203 Pb-DOTA-Re(Arg 11 )CCMSH exhibited a peak tumor-to-kidney uptake ratio of 1.53 at 2 h after injection. The absorbed doses to the tumor and kidneys were 4.32 and 4.35 Gy, respectively, per 37 MBq. Whole-body clearance of 203 Pb-DOTA-Re(Arg 11 )CCMSH was fast, with approximately 89% of the injected activity cleared through the urinary system by 2 h after injection. 203 Pb showed 1.6-mm SPECT resolution, which was comparable to 99m Tc. Melanoma lesions were visualized through SPECT/CT images of 203 Pb-DOTA-Re(Arg 11 )CCMSH at 2 h after injection. Conclusion: 203 Pb-DOTA-Re(Arg 11 )CCMSH exhibited favorable pharmacokinetic and tumor imaging properties, highlighting its potential as a matched-pair SPECT agent for 212 Pb-DOTA-Re(Arg 11 )CCMSH melanoma treatment.

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“…Clear and distinct γ-camera images of LS-174T tumors were obtained by injection of 203 Pb-DOTA-B72.3 (Figure 3). 78 Miao et al also evaluated DOTA-Re(Arg11)CCMSH radiolabeled with 203 Pb as a matched pair imaging agent for 212 Pb- DOTA-Re(Arg11)CCMSH 79 . 203 Pb- DOTA-Re(Arg11)CCMSH exhibited high melanoma uptake and a biodistribution pattern similar to that of 212 Pb-DOTA-Re(Arg11)CCMSH, highlighting its potential as a matched pair imaging probe for 212 Pb-DOTA-Re(Arg11)CCMSH (Figure 4).…”

Section: Applications Of 203pbmentioning

confidence: 99%

Towards translation of 212Pb as a clinical therapeutic; getting the lead in!

Yong

Brechbiel

2011

Dalton Trans.

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Targeted α-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissue than β-emitters because of the combination of short path length (50-80 μm) with the high linear energy transfer (100 KeV μm −1 ) of this emission. These physical properties offer the real possibility of targeted (pre-targeted) α-therapy suitable for the elimination of minimal residual or micrometastatic disease. Targeted and pre-targeted radioimmunotherapy (RIT) using α-emitters such as 212 Bi (T 1/2 = 1.01 h) and 212 Pb (T 1/2 =10.6 h) has demonstrated significant utility in both in vitro and in vivo model systems. 212 Pb, a promising α-particle emitting source, is the longer-lived parent nuclide of 212 Bi, and serves as an in vivo generator of 212 Bi. The radionuclide has been successfully used in RIT and pre-targeted RIT and demonstrated the enhanced therapeutic efficacy in combination with chemotherapeutics, such as gemcitabine and paclitaxel. The following perspective addresses the modes of radionuclide production, radiolabeling and chelation chemistry, as well as the application of 212 Pb to targeted and pre-targeted radiation therapy.

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In vivo evaluation of a lead-labeled monoclonal antibody using the DOTA ligand

Cited by 19 publications

References 17 publications

The Antitumor and Immunoadjuvant Effects of IFN-α in Combination with Recombinant Poxvirus Vaccines

The Antitumor and Immunoadjuvant Effects of IFN-α in Combination with Recombinant Poxvirus Vaccines

²⁰³Pb-Labeled α-Melanocyte–Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

Towards translation of 212Pb as a clinical therapeutic; getting the lead in!

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In vivo evaluation of a lead-labeled monoclonal antibody using the DOTA ligand

Cited by 19 publications

References 17 publications

The Antitumor and Immunoadjuvant Effects of IFN-α in Combination with Recombinant Poxvirus Vaccines

The Antitumor and Immunoadjuvant Effects of IFN-α in Combination with Recombinant Poxvirus Vaccines

203Pb-Labeled α-Melanocyte–Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

Towards translation of 212Pb as a clinical therapeutic; getting the lead in!

Contact Info

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²⁰³Pb-Labeled α-Melanocyte–Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection