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J Nucl Med. 2008; 49 (Supplement 1):327P
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Oncology-Basic Science: Therapy, Metrics & Intervention

Therapy, Metrics & Intervention Posters

Pre-clinical development of a 188Re-labeled melanin-binding antibody for phase I clinical trial in patients with metastatic melanoma

Ekaterina Dadachova1, Ekaterina Revskaya1, Muctarr Sesay2, Robertha Howell1, George Thornton3, Arut Natarajan4, Gary Mirick4, Sally DeNardo4, Gerald DeNardo4 and Arturo Casadevall1

1 Albert Einstein College of Medicine, Bronx, New York; 2 Goodwin Biotechnology, Plantation, Florida; 3 Pain Therapeutics, Inc., South San Francisco, California; 4 University of California, Davis Medical Center, Sacramento, California


Formula

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Objectives: Effective methods of treatment of currently deadly metastatic melanoma are urgently needed. Previously we established the feasibility of targeting melanin in experimental human melanoma with 188-Rhenium (188Re)-labeled 6D2 mAb resulting in tumor regression. We carried out additional pre-clinical development of 188Re-6D2 for use in Phase I clinical trial in patients with metastatic melanoma.

Methods: The developmental work included chemistry, pharmacokinetics, efficacy, and acute hematologic toxicity studies in an experimental human melanoma.

Results: Tris(2-Carboxyethyl) Phosphine Hydrochloride (TCEP) was tested as potential agent for generation of –SH groups on 6D2 mAb for subsequent radiolabeling with 188Re. TCEP turned out to be both effective in generating a sufficient number of -SH groups on 6D2 mAb to ensure high radiolabeling yields and facile in preserving mAbs structural integrity. 188Re-6D2 cleared from the blood with the half-life of approximately 5 hrs and from the body – with the half-life of 10 hr. Therapy of A2058 melanoma tumor-bearing mice showed that while the lowest dose of 0.15 mCi per mouse had no effect on the tumor progression relative to untreated mice - doses of 0.5, 1.0 and 1.5 mCi significantly (P<0.05) slowed down the tumor growth. Transient effects of RIT on WBC and platelet resolved by Day 14 post-treatment.

Conclusions: 188Re-6D2 was immunoreactive and stable over time, cleared fast from the blood and major organs and was therapeutic in experimental human melanoma.

Research Support: Pain Therapeutics, Inc. and AECOM Cancer Center.





This Article
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Right arrow Email this article to a friend
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Right arrow Alert me to new issues of the journal
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Google Scholar
Right arrow Articles by Dadachova, E.
Right arrow Articles by Casadevall, A.
PubMed
Right arrow Articles by Dadachova, E.
Right arrow Articles by Casadevall, A.