Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb

Chappell, Lara L.; Dadachova, Ekaterina; Milenic, Diane E.; Garmestani, Kayhan; Wu, Chao‐Liang; Brechbiel, Martin W.

doi:10.1016/s0969-8051(99)00086-4

Cited by 127 publications

(105 citation statements)

References 30 publications

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“…The synthesis, characterization, and purification of the bifunctional ligand TCMC has been previously described (27,28). Trastuzumab was conjugated with TCMC by established methods using a 10-fold molar excess of ligand to mAb (29).…”

Section: Methodsmentioning

confidence: 99%

Potentiation of High-LET Radiation by Gemcitabine: Targeting HER2 with Trastuzumab to Treat Disseminated Peritoneal Disease

Milenic¹,

Garmestani²,

Brady³

et al. 2007

Clinical Cancer Research

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Section: Methodsmentioning

confidence: 99%

Potentiation of High-LET Radiation by Gemcitabine: Targeting HER2 with Trastuzumab to Treat Disseminated Peritoneal Disease

Milenic¹,

Garmestani²,

Brady³

et al. 2007

Clinical Cancer Research

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“…16,17 The final concentration of trastuzumab and HuIgG was determined by the method of Lowry using a bovine serum albumin (BSA) standard. 18 The number of CHX-A †-DTPA or TCMC molecules linked to each of the preparations was determined using spectrophotometric assays based on the titration of either the yttriumor lead-Arsenazo(III) complex, respectively.…”

Section: Chelate Synthesis and Monoclonal Antibody Conjugationmentioning

confidence: 99%

Evaluation of Platinum Chemotherapy in Combination with HER2-Targeted α-Particle Radiation

Milenic

Baidoo

Shih

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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The studies described herein assess the potential of combining platinum-based chemotherapy with high-linear energy transfer (LET) a-particle-targeted radiation therapy using trastuzumab as the delivery vehicle. An initial study explored the combination of cisplatin with 213 Bi-trastuzumab in the LS-174T i.p. xenograft model. This initial study determined the administration sequence of cisplatin and 213 Bi-trastuzumab. Cisplatin coinjected with 213 Bi-trastuzumab increased the median survival (MS) to 90 days versus 65 days for 213 Bi-trastuzumab alone. Toxicity was observed with a weight loss of 17.6% in some of the combined treatment groups. Carboplatin proved to be better tolerated. Maximal therapeutic benefit, that is, a 5.1-fold increase in MS, was obtained in the group injected with 213 Bi-trastuzumab, followed by carboplatin 24 hours later. This was further improved by administration of multiple weekly doses of carboplatin. The MS achieved with administration of 3 doses of carboplatin was 180 days versus 60 days with 213 Bi-trastuzumab alone. The combination of carboplatin with 212 Pb radioimmunotherapy was also evaluated. The therapeutic efficacy of 212 Pb-trastuzumab (58-day MS) increased when the mice were pretreated with carboplatin 24 hours prior (157-day MS). These results again demonstrate the necessity of empirically determining the administration sequence when combining therapeutic modalities.

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“…Macrocylic structures are extremely favorable for metal complexation. The strong affinity shown by polyamines and their selective binding of certain metals result in their use as metal catalysts [5], the active sites of metalloenzymes [6][7][8], agents which cleave phosphate esters [9,10] including DNA [11] and RNA [12], molecular luminescence probes [13], MRI contrast agents [14], and nuclear radiophamaceuticals for diagnosis [15][16][17] and therapy [18].…”

Section: Introductionmentioning

confidence: 99%

A New Synthesis of TE2A—a Potential Bifunctional Chelator for 64Cu

Pandya

Kim

Kwak

et al. 2010

Nucl Med Mol Imaging

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Purpose The development of a new bifunctional chelator, which holds radiometals strongly in living systems, is a prerequisite for the successful application of diseasespecific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu(II) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator. Methods TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive deprotection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with 64 Cu and microPET imaging was performed to follow the clearance pattern of the 64 Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with 64 Cu. Results TE2A was prepared in salt-free form from cyclam in an overall yield of 74%. The microPET images showed that 64 Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through one carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with 64 Cu in 94% yield within 30 min. Conclusion TE2A can be used by itself as a bifunctional chelator without any further structural modification.

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Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb

Cited by 127 publications

References 30 publications

Potentiation of High-LET Radiation by Gemcitabine: Targeting HER2 with Trastuzumab to Treat Disseminated Peritoneal Disease

Potentiation of High-LET Radiation by Gemcitabine: Targeting HER2 with Trastuzumab to Treat Disseminated Peritoneal Disease

Evaluation of Platinum Chemotherapy in Combination with HER2-Targeted α-Particle Radiation

A New Synthesis of TE2A—a Potential Bifunctional Chelator for 64Cu

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