Biodistributions of intact monoclonal antibodies and fragments of BLCA-38, a new prostate cancer directed antibody.
BACKGROUND
Monoclonal antibodies (MAbs) are used for targeting agents to tumours while minimizing normal tissue exposure.


METHODS
A new anti-prostate cancer MAb, BLCA-38, was radioiodinated (I125) and assessed for its ability to target subcutaneous human prostate cancer (DU-145) xenografts after systemic intraperitoneal administration. For comparison, the profile of J591 MAb (now in clinical trial) against LNCaP-LN3 tumours was examined. Biodistribution profiles were obtained at various times, by assessing injected dose/gram (%ID/g) and xenograft to blood (X/B) ratios. Microautoradiography of xenografts was performed. After conjugation with a melittin peptide toxin, the profiles of BLCA-38 and J591 were compared with that of an irrelevant antibody, DS-1.


RESULTS
Xenograft localization by 125I-labeled BLCA-38 and J591 MAbs to their relevant antigen-positive tumors was comparable, and there was no unusual localization in nontumour tissues. F(ab')2 and Fab fragments gave improved X/B ratios, but the %ID/g xenograft was decreased and they accumulated in kidneys, bladder and stomach. In contrast, the conjugates of irrelevant antibody showed no tumour targeting. Microautoradiography showed more tumour accumulation of MAbs than F(ab')2s or Fabs.


CONCLUSIONS
BLCA-38 can target prostate cancer in vivo almost as effectively as J591. Given that J591 is used clinically, BLCA-38, which targets a different antigen, has potential for radioimmunoscintigraphy and for therapeutic targeting of prostate cancer.
Carter
Teresa
T
School of Clinical Medicine, University of New South Wales, Sydney, Australia.
Sterling-Levis
Katy
K
Ow
Kim
K
Doughty
Larissa
L
Hattarki
Meghan
M
Shapira
Deborah
D
Hewish
Dean
D
Kortt
Alexander A
AA
Russell
Pamela J
PJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007274:Injections, Intraperitoneal; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism; D008297:Male; D008555:Melitten / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000276:immunology*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D008555:Melitten