Tc-99m labeled anti CEA F(ab{prime}){sub 2}: Augmenting tumor uptake with anitbody:Interferon (MAb:IFN-{alpha}-2b) conjugate

Journal Article · Wed May 01 04:00:00 EDT 1996 · Journal of Nuclear Medicine

OSTI ID:447771

Thakur, M L; Donegan, M; Li, J ^[1]

---

1. Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States); and others

Previously we have shown that IFN-{alpha}-2b, a potent biological response modifier (BRM) significantly enhanced tumor uptake of radiolabeled MAbs. Results were attributed to increased blood flow and upregulation of cell surface receptor glycoproteins. Probably because of the blood flow increase in all organs, radioactivity levels in other tissues, although to a lesser extent, were also enhanced. In order to validate our hypothesis that selective tumor targeting of IFN-{alpha}-2b (Schering-Plough, N.J.) may enhance tumor uptake and diminish uptake in normal organs, IFN-{alpha}-2b was conjugated with anti CEA MAb F-6 (IgG2a), by reacting with 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (CMC) and N-hydroxysulfosuccinimide (NHS) in a 1:2:50:50 ratio by weight at pH 9.2 (22{degrees}C) for 24 hr. The conjugate (30{mu}g) was administered i.v. to nude mice bearing human colorectal carcinoma LS174T, 3hr prior to the i.v. administration of 300uCi / 20ug (1.5Ci / uM) F-6F(ab{prime}){sub 2}. Animals not receiving the conjugate served as controls. The conjugation efficiency as determined using I-125-IFN-{alpha}-2b was >70% and MAb:IFN-{alpha}-2b ratio was approximately 1:1. In animals receiving IFN conjugate tumor uptake enhanced by 180% and liver uptake decreased to 56%. Radioactivity also decreased in most other tissues. Furthermore with conjugate, the tumor/muscle ratio increased by 210% (10 {plus_minus} 1.2 Vs 4.7 {plus_minus} 0.5), tumor/blood ratio by 220% (5.4 {plus_minus} 0.6 Vs 2.5 {plus_minus} 0.3), and tumor/liver ratio by 317% (0.7 {plus_minus} 0.1 Vs 0.2 {plus_minus} 0.05).

• DOE Contract Number: FG02-92ER61485
• OSTI ID: 447771
• Report Number(s): CONF-960659--
• Journal Information: Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 37; ISSN 0161-5505; ISSN JNMEAQ
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BLOOD FLOW
CARCINOMAS
INTERFERON
LABELLED COMPOUNDS
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
RADIATION DOSES
RADIOIMMUNOTHERAPY
SYNTHESIS
TECHNETIUM 99
TUMOR CELLS
UPTAKE