title: Pretargeted gamma imaging of murine metastatic melanoma lung lesions with bispecific antibody and radiolabeled polymer drug conjugates.
abstract: BACKGROUND
  Bispecific monoclonal antibodies (bsMAbs) have been developed as a pretargeting tool to reduce background activity, thereby increasing target to background (T : B) ratios. To enhance visualization of small lesions in vivo, we have used the pretargeting approach of bsMAb and negatively charged polymers radiolabeled with high-specific radioactivity.
  
  
  METHODS
  Imaging of metastatic melanoma lesions localized in lung tissues pretargeted with bsMAb and targeted with high-specific radioactivity polymers was carried out. The bsMAb was prepared by covalent conjugation of an antinucleosomal antibody (2C5) recognizing a nucleosomal pan cancer antigen and an anti-diethylene triaminepentaacetic acid antibody (6C31H3) by means of thioether linkage. BsMAb was injected intravenously 10 days after the initiation of the induction of murine melanoma metastasized to the lungs. The next day, 37 MBq ⁹⁹mTc-diethylene triaminepentaacetic acid-succinylated polylysine were injected intravenously and in-vivo imaging was carried out after the injection. In-vivo and ex-vivo target (T) to background (B) activity ratios were assessed by computer planimetry and biodistribution studies.
  
  
  RESULTS
  Lesions were visualized unequivocally in 3 h by gamma scintigraphy. Ex-vivo gamma-scintillation counting corrected for the lesion mass showed that the mean lesion activity was 24.85 ± 13.53 percent injected dose per gram when pretargeted with bsMAb, whereas it was 0.977 ± 0.465 percent injected dose per gram (P<0.01) in the control group injected only with radioactive polymers also corrected similarly.
  
  
  CONCLUSIONS
  The use of bsMAb complexes and ⁹⁹mTc-diethylene triaminepentaacetic acid-succinylated polylysine enabled early in-vivo visualization of small metastatic melanoma lesions in the lungs.
authors: Department of Pharmaceutical Sciences, Bouve College of Health Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts 02115, USA.
authors: Keyur S
authors: KS
authors: Gada
authors: Vishwesh
authors: V
authors: Patil
authors: Rajiv
authors: R
authors: Panwar
authors: Stan
authors: S
authors: Majewski
authors: Yared
authors: Y
authors: Tekabe
authors: Ban-An
authors: BA
authors: Khaw
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm / Q000276:immunology; D005240:Feasibility Studies; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D004369:Pentetic Acid; D011108:Polymers; D019275:Radiopharmaceuticals; D012878:Skin Neoplasms / Q000000981:diagnostic imaging*; D013667:Technetium; D017556:Technetium Compounds; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D011108:Polymers; D019275:Radiopharmaceuticals; D017556:Technetium Compounds; D013667:Technetium; D004369:Pentetic Acid