Yttrium-90/indium-111 DOTA peptide chimeric L6; pharmacokinetics, dosimetry and initial therapeutic studies in patients with breast cancer
- Univ. of California, Sacramento, CA (United States); and others
Chimeric L6 MoAb(ChL6) as I-131 ChL6 has shown therapeutic promise in breast cancer patients. To enhance this potential, we developed yttrium-90 (Y-90) and indium-111 (In-111) ChL6 radiopharmaceuticals by conjugating Y-90 and In-111 DOTA peptide ChL6. Immunoreactivity of In-111 and Y-90 ChL6 was 80-100% of ChL6. Dosimetry was calculated from pharmacokinetics obtained in four studies of patients with metastatic breast cancer using 200 mg ChL6 and 4mCi In-111/3mCi Y-90 DOTA peptide ChL6 in 3 studies and 10 mCi In-111 in one (specific activity 1.1-3.5mCi/mg). Quantitative imaging of In-111 and in vitro analysis of Y-90/In-111 blood and urine clearances and biopsies for bone and marrow uptake were performed. In-111 and Y-90 DOTA peptide ChL6 blood clearances were compared in each patient with {beta} intercepts for each initial study of 13.9/12.7, 4.9/5.8, 25.2/16.2 (%ID), and {beta} T{1/2} 32/30, 33/35, and 41/57 (h) for In- 111/Y-90, respectively. Normal organ and tumor dosimetry for Y-90 DOTA peptide ChL6 was extrapolated from the In-111 kinetics: WB 2.1-2.3, Liver 3.8-5.9, Lung 6.2-7.9, Kidney 8.1-11.3, Spleen 4.4-14.0 (cGy/mCi). Dosimetry of 13 tumored areas (1-10 g) ranged from 42-260 (mean = 103) cGy/mCi. Marrow doses calculated from Y-90 in blood ranged from 0.6-1.5. Marrow biopsies at 5 d pi showed In-111 and Y-90 (%ID/g), 1-2 x 10{sup -3} and 6-7x10{sup -4} and bone 1-3x10{sup -3} and 0.1-3x10{sup -4}, respectively. Compared to our previous I-131 ChL6 dosimetry, this study indicates that the Y-90 DOTA peptide ChL6 radiation dose to tumor is 4-8 times that of I-131 ChL6 whereas normal organs receive less than twice that of I-131 from Y-90. Based on this calculated enhancement of the therapeutic ratio, a multicycle Y-90 DOTA peptide ChL6 therapy protocol has been initiated in breast cancer patients.
- DOE Contract Number:
- FG03-84ER60233
- OSTI ID:
- 441607
- Report Number(s):
- CONF-950603-; ISSN 0161-5505; CNN: Grant NCl CA47829; TRN: 96:002093-0032
- Journal Information:
- Journal of Nuclear Medicine, Vol. 36, Issue Suppl.5; Conference: 42. annual meeting of the Society of Nuclear Medicine, Minneapolis, MN (United States), 12-15 Jun 1995; Other Information: PBD: May 1995
- Country of Publication:
- United States
- Language:
- English
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