Abstract | UNLABELLED: METHODS: hEGF was derivatized with diethylenetriamine pentaacetic acid ( DTPA) and radiolabeled with 111In-acetate. The internalization of 111In-DTPA-hEGF by MDA-MB-468 breast cancer cells (1.3x10(6) EGFRs/cell) was determined by displacement of surface-bound radioactivity by an acid wash. The radioactivity in the cell nucleus and chromatin, isolated by differential centrifugation, was measured. The effect on the growth rate of MDA-MB-468 or MCF-7 (1.5x10(4) EGFRs/cell) cells was determined after treatment in vitro with 111In-DTPA-hEGF, unlabeled DTPA-hEGF, or 111In-DTPA. The surviving fraction of MDA-MB-468 or MCF-7 cells treated in vitro with 111In-DTPA-hEGF was determined in a clonogenic assay. The radiotoxicity in vivo against normal hepatocytes or renal tubular cells was evaluated by measuring alanine aminotransferase (ALT) or creatinine levels in mice administered high amounts of 111In-DTPA-hEGF (equivalent to human doses up to 14,208 MBq) and by light and electron microscopy of the tissues. RESULTS: Approximately 70% of 111In-DTPA-hEGF was internalized by MDA-MB-468 cells within 15 min at 37 degrees C and up to 15% was translocated to the nucleus within 24 h. Chromatin contained 10% of internalized radioactivity. The growth rate of MDA-MB-468 cells was decreased 3-fold by treatment with 111In-DTPA-hEGF (45-60 mBq/cell). Treatment with unlabeled DTPA-hEGF caused a 1.5-fold decrease in growth rate, whereas treatment with 111In-DTPA had no effect. Targeting of MDA-MB-468 cells with up to 130 mBq/cell of 111In-DTPA-hEGF resulted in a 2-logarithm decrease in their surviving fraction. No decrease in the growth rate or surviving fraction of MCF-7 cells was evident. There was no evidence of hepatotoxicity or renal toxicity in mice administered high amounts of 111In-DTPA-hEGF. Radiation dosimetry estimates suggest that the radiation dose to an MDA-MB-468 cell targeted with 111In-DTPA-hEGF could be as high as 25 Gy with up to 19 Gy delivered to the cell nucleus. CONCLUSION:
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Authors | R M Reilly, R Kiarash, R G Cameron, N Porlier, J Sandhu, R P Hill, K Vallis, A Hendler, J Gariépy |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 41
Issue 3
Pg. 429-38
(Mar 2000)
ISSN: 0161-5505 [Print] United States |
PMID | 10716315
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Indium Radioisotopes
- Epidermal Growth Factor
- ErbB Receptors
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Topics |
- Animals
- Breast Neoplasms
(pathology, radiotherapy)
- Epidermal Growth Factor
(pharmacology)
- ErbB Receptors
(metabolism)
- Female
- Humans
- In Vitro Techniques
- Indium Radioisotopes
(pharmacology)
- Kidney
(pathology)
- Liver
(pathology)
- Mice
- Mice, Inbred BALB C
- Microscopy, Fluorescence
- Radiation Dosage
- Radiotherapy
- Tumor Cells, Cultured
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