Effect of size of radiolabeled antibody and fragments on tumor uptake and distribution in nephrectomized mice
The importance of molecular size in tumor (T) uptake of intact monoclonal antibody (MAb) of MAb fragments (frag.) is difficult to assess because frag. are excreted by the kidney. To obviate this problem nephrectomized nude mice (M) bearing carcinoembryonic (CEA) secreting human colon (T) were used in the following experiments. Following nephrectomy 3 groups of M were injected intravenously with intact In-111 anti-CEA MAb and simultaneously with I-125 intact, F(ab')2 or Fab anti-CEA-MAb. Iodination was by chloramine T and In-111 labeling by bifunctional chelation. All M were killed 8 h after injection, T and normal tissues (NT) dissected, weighed, and counted against a standard of the injectate. The distribution of intact I-125 and In-111-MAb were nearly identical allowing In-111-MAb to be used for comparison with the I-125 frag. T concentration (conc.) of I-125-F(ab')2 were 25% greater and L conc. were 63% lower than for intact In-111-MAb. T conc. of I-125-Fab were 86% greater and L conc. 64% lower than for intact In-111-MAb. Large T, which produce higher serum CEA levels, increased the L conc. of intact MAb but not I-125 frag. The authors conclude that when renal excretion is prevented there is (a) an inverse relationship between size of a MAb moiety and its T conc. indicating that the improved T/NT ratios observed with frag. are not due only to renal excretion, and (b) the Fc portion of the MAb appears to be critical for L uptake of MAb or immune complexes.
- Research Organization:
- Ludwig Institute, Lausanne
- OSTI ID:
- 6781170
- Report Number(s):
- CONF-840619-; TRN: 87-008836
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 25:5; Conference: 31. annual meeting of the Society of Nuclear Medicine, Los Angeles, CA, USA, 5 Jun 1984
- Country of Publication:
- United States
- Language:
- English
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INDIUM 111
DIAGNOSTIC USES
IODINE 125
MICE
NEOPLASMS
MONOCLONAL ANTIBODIES
LABELLING
RENAL CLEARANCE
ANTIGENS
HUMAN POPULATIONS
KIDNEYS
LARGE INTESTINE
QUANTITY RATIO
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TRACER TECHNIQUES
UPTAKE
ANIMALS
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BETA DECAY RADIOISOTOPES
BODY
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DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
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ELECTRON CAPTURE RADIOISOTOPES
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GASTROINTESTINAL TRACT
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
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IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ORGANS
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550601* - Medicine- Unsealed Radionuclides in Diagnostics