TAG-72 as a Tumor Marker

Schlom, Jeffrey; Colcher, David; Milenic, Diane E.; Hand, Patricia Horan; Greiner, John W.; Kuroki, Masahide; Thor, Ann D.; Molinolo, Alfredo A.; Ohuchi, Noriaki

doi:10.1007/978-1-4612-0401-5_18

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…The expression of TAG-72 and the reactivity of MAb B72.3 have been extensively studied. 26 The stability and efficacy of these ligands for radioimmunotherapy with bismuth radioisotopes and MAb B72.3 are the focus of the study presented here. The six derivatives of DTPA assessed are SCN-Bz-, 1B4M-, 1B3M-, 1M3B-and the cyclohexyl isomers, CHX-A and CHX-B ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

In VivoEvaluation of Bismuth-Labeled Monoclonal Antibody Comparing DTPA-Derived Bifunctional Chelates

Milenic¹,

Roselli²,

Mirzadeh³

et al. 2001

Cancer Biotherapy and Radiopharmaceuticals

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Among the radionuclides considered for radioimmunotherapy, alpha-emitters such as the bismuth isotopes, 212Bi and 213Bi, are of particular interest. The macrocyclic ligand, DOTA, has been shown to form stable complexes with bismuth isotopes. The kinetics of the complexation of bismuth with the DOTA chelate, however, are slow and impractical for use with 212Bi and 213Bi that have half-lives of 60.6 and 45.6 min. The study described herein compares six DTPA derived bifunctional chelates with the goal of identifying an alternative to the DOTA ligand for radiolabeling with bismuth. Radioimmunoconjugates comprised of MAb B72.3, each of the six DTPA chelates, and radiolabeled with 206Bi, which facilitated the evaluation due to its readily detectable gamma-emission. In vitro studies showed that each of the radioimmunoconjugates retained immunoreactivity that was comparable to its 125I-labeled counterpart. The 206Bi- and 125I-labeled immunoconjugates were then co-injected i.p. into normal athymic mice. Injection of Afree@ 206Bi demonstrated that the kidneys were the critical organ to evaluate for retention of bismuth in the chelate complex. Major differences were identified among the six preparations. The CHX-A and -B immunoconjugates were found to have 1) the lowest %ID/gm in the kidney; 2) a level of 206Bi in the kidney that was comparable to that of 125I-B72.3; and 3) no significant uptake of 206Bi evident in other organs such as bone, lung and spleen. The results described herein suggest that either of the cyclohexyl derivatives of DTPA may be suitable candidates for the labeling of immunoconjugates with alpha-emitting bismuth isotopes for radioimmunotherapeutic applications.

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Section: Introductionmentioning

confidence: 99%

In VivoEvaluation of Bismuth-Labeled Monoclonal Antibody Comparing DTPA-Derived Bifunctional Chelates

Milenic¹,

Roselli²,

Mirzadeh³

et al. 2001

Cancer Biotherapy and Radiopharmaceuticals

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“…T h e antibodies are used in an unconjugated or 'naked' form as passive therapy or as vaccines, or as vehicles for delivery of toxic agents such as drugs, toxins and isotopes to the tumour cells [2,5]. Affinity binding, molecular size of antibody form and antigen expression on the tumour are among the features that can now be manipulated to increase the effectiveness of these agents for tumour targeting [6].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic monoclonals

Boleti

George

Epenetos

1995

Biochemical Society Transactions

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

Milenic

Roselli

Brechbiel

et al. 1998

European Journal of Nuclear Medicine and Molecular Imaging

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The aim of this study was to assess the utility of a radioimmunoconjugate containing a lead radionuclide for therapy and scintigraphy applications. The radioimmunoconjugate evaluated consisted of a bifunctional DOTA ligand and monoclonal antibody (MAb) B72.3 using athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. In the studies reported here, the lead-203-DOTA complex itself was first demonstrated to have in vivo stability. MAb B72.3 was then conjugated with the DOTA ligand and labeled with 203Pb, and the immunoreactivity of B72.3 was maintained. The localization of the radioimmunoconjugate to tumor tissue and other select organs paralleled that of DOTA-125I-B72.3, suggesting a similar metabolic pattern of the two radioimmunoconjugates. Thus, the DOTA-metal complex does not alter the behavior of the radioimmunoconjugate. Tumor localization of the 203Pb-DOTA-B72.3 conjugate was demonstrated with biodistribution studies as well as immunoscintigraphy studies. Such data highlight the stability of a lead radionuclide in the DOTA ligand. The suitability of this chelation chemistry for labeling radioimmunoconjugates with a lead radionuclide now makes its application in nuclear medicine a feasible proposition.

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TAG-72 as a Tumor Marker

Cited by 4 publications

References 30 publications

In VivoEvaluation of Bismuth-Labeled Monoclonal Antibody Comparing DTPA-Derived Bifunctional Chelates

In VivoEvaluation of Bismuth-Labeled Monoclonal Antibody Comparing DTPA-Derived Bifunctional Chelates

Therapeutic monoclonals

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

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