90Y.B72.3 against pancreatic cancer: dosimetric and biological analysis.
Nude mice xenografted with a human pancreatic carcinoma cell line were injected with yttrium-90 (90Y) conjugated to diethylene triaminepenta acetic acid (DTPA) alone, and DTPA covalently linked to a monoclonal antibody, B72.3. The animals were sacrificed in temporal sequence to evaluate isotope distribution. Dosimetry was carried out using the principles outlined in MIRD and ICRU Report 32. Results are expressed as percent uptake per unit mass in organs and tumor and as relative absorbed dose normalized to 90Y uptake in liver at 7 hr. When conjugated to B72.3, an 8-fold increase in isotope localization in the tumor was noted by 24 hr. When the relative absorbed dose is calculated for 90Y and 90Y.B72.3, a 26-fold increase in tumor dose is noted for the 90Y conjugate. Normal tissues show no to modest (less than 5x) enhanced dose with 90Y.B72.3. B72.3, therefore, deserves further investigation as a potential monoclonal antibody for targeting therapeutic radioisotopes and possibly diagnostic radioisotopes to pancreatic cancer. Radiobiological aspects of the low dose rates from radioimmunotherapy are discussed.
Department of Human Oncology, Wisconsin Clinical Cancer Center University of Wisconsin, Madison, WI 53792.
M P
MP
Mehta
S S
SS
Kubsad
J F
JF
Fowler
A K
AK
Verma
J T
JT
Hsieh
T J
TJ
Kinsella
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002277:Carcinoma / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D004369:Pentetic Acid / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; D004369:Pentetic Acid