Concurrent radiotherapy and tumor targeting with 111In-HMFG1-F(ab')2 in patients with MUC1-positive non-small cell lung cancer.
BACKGROUND
Combining external radiotherapy (XRT) and radioimmunotargeting might enhance tumor radiation without affecting morbidity, due to different toxicity profiles.


OBJECTIVE
To assess 111In-F(ab')2-HMFG1 biodistribution, the influence of "low-dose" lysine on F(ab')2 renal uptake and provide data forfurther concurrent XRT and RIT.


METHODS
Twenty-three patients received injections of 111n-HMFG1-F(ab')2, with or without lysine co-infusion, 7 and 21 days after the initiation of XRT. Whole-body images, blood and urine activity were monitored.


RESULTS
Despite clear visualization of 111In-F(ab')2-HMFG1, the residence time and absorbed dose in tumors were low. The co-infusion of "low-dose" lysine did not reduce renal uptake, thus contradicting previously published results. The biodistribution differences after the first and the second injection might be attributed to human anti-mouse antibody (HAMA) response or Ag-complexation.


CONCLUSIONS
Low-dose lysine is not feasible. Larger amounts of lysine during extended infusion time are therefore advocated. It is proposed that repeated MAb injection be given during the first fractions of XRT.
Garkavij
Michael
M
Department of Oncology, Lund University Hospital, SE-221 85, Lund, Sweden. Michael.Garkavij@med.lu.se
Samarzija
Miroslav
M
Ewers
Sven B
SB
Jakopovic
Marko
M
Tezak
Stanko
S
Tennvall
Jan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism / Q000627:therapeutic use; D007205:Indium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017879:Isothiocyanates / Q000493:pharmacokinetics / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008239:Lysine / Q000031:analogs & derivatives / Q000627:therapeutic use; D008875:Middle Aged; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000096:biosynthesis / Q000378:metabolism*; D009367:Neoplasm Staging; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D016499:Radioimmunotherapy / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
C100700:6-(4-isothiocyanatobenzyl)-diethylenetriamine pentaacetic acid; D000596:Amino Acids; D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D007205:Indium Radioisotopes; D017879:Isothiocyanates; D018396:Mucin-1; D019275:Radiopharmaceuticals; C469215:pemtumomab; D004369:Pentetic Acid; D008239:Lysine