# RADIOLABELED MONOCLONAL ANTIBODIES FOR CANCER THERAPY

> **NIH NIH R01** · OAK RIDGE ASSOCIATED UNIVERSITIES · 1988 · $173,302

## Abstract

Monoclonal antibodies and monoclonal antibody fragments will be
labeled with the beta-emitting radionuclide, yttrium-90 (90Y, T
1/2 = 64.- hr), and studied preclinically to assess their potential as
agents for radioimmuntherapy of cancer.  Bifunctional chelate
techniques which will give enhanced in vivo stability will be
developed in order to circumvent the high bone and
reticuloendothelial uptakes and consequent dose-limiting bone
marrow toxicity associated with currently available methods for
production of 90Y-labeled monoclonal antibodies.  Monoclonal
antibody CO17-1A, which has specificity for colorectal and
pancreatic carcinomas, will be chelate conjugated using the new
bifunctional chelate techniques.  Radioimmunoassay will be used
to monitor retention of immunoreactivity following conjugation.
Tissue distribution studies of 90Y-labeled CO17-1A in athymic
nude mice bearing xenografts of human colorectal carcinoma cell
line SW 948 will permit assessment of the potential of the new
bifunctional chelate techniques.  Control studies will be used to
evaluate the importance of nonspecific binding.  Absorbed
radiation dose calculations will enable selection of tumoricidal
dosages of 90Y-labeled CO17-1A for use in tumor
growth/regression studies in nude mice bearing tumor xenografts.
Calcium DTPA encapsulated in large unilamella vesicle (LUV)
liposomes will be evaluated for decorporation of the 90Y which
becomes dissociated in vivo from 90Y-labeled CO17-1A via either
catabolism or "leakage."  Use of the radioprotective drug, WR-
2721, as an adjunct to 90Y-labeled monoclonal antibody therapy
for reducing the radiation dose to the bone marrow will be
studied.  WR-2721 will also be coupled to monoconal antibody
16B-13, which has specificity for the bone marrow, in order to
direct the radioprotective effect more specifically to that organ.
The research will be extended to other monoclonal antibodies
against gastrointestinal tumors (BR55-2 and 1116-NS-19-9) and
melanoma (ME-361 and 691-19-19), as well as Fab and F(ab')2
fragments of monoclonal antibodies.  This multidiscplinary
research approach, which combines the fields of bio-organic
chemistry, immunochemistry, and radiopharmacology, is aimed at
development of improved methods for radioimmunotherapy of
cancer in man.

## Key facts

- **NIH application ID:** 3179052
- **Project number:** 2R01CA039706-04
- **Recipient organization:** OAK RIDGE ASSOCIATED UNIVERSITIES
- **SAM.gov UEI:** JW7MLW3RRK34
- **Principal Investigator:** LEE CROSS WASHBURN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $173,302
- **Award type:** 2
- **Project period:** 1985-09-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179052

## Citation

> US National Institutes of Health, RePORTER application 3179052, RADIOLABELED MONOCLONAL ANTIBODIES FOR CANCER THERAPY (2R01CA039706-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179052. Licensed CC0.

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