title: Development of a single vial kit formulation of [99mTc]-labeled doxorubicin for tumor imaging and treatment response assessment-preclinical evaluation and preliminary human results.
abstract: The present study describes the successful radiolabeling of [99mTcO(-) 4 ] with doxorubicin, and the resultant product was formulated in to a ready-to-label lyophilized single vial kit preparation for convenient use in a routine clinical setting. The radiolabeled preparation of [99mTc]-doxorubicin exhibited a high radiolabeling efficiency of more than 95.0%, serum stability for up to 24 h, and shelf-life of lyophilized cold kits was more than 6 months. Animal imaging data in tumor-bearing mice demonstrated that [99mTc]-doxorubicin accumulated in the tumor site with high target (tumor) to non-target (contra-lateral thigh) ratio (3.2 ± 0.5). The ratio decreased to 1.2 ± 0.6 indicating a good response on follow up imaging performed after 2 weeks of doxorubicin treatment. [99mTc]-doxorubicin scintigraphic data in human volunteers supported the hepato-renal excretion of the radiotracer as reflected by the increased accumulation of the radiotracer as a function of time in intestine, kidneys, and urinary bladder. Further, imaging in patients (very limited number) indicated that the technique may be useful in the detection of active sarcoma and post treatment (surgery/chemotherapy) remission or absence of the disease. The technique, however, needs validation through further preclinical evaluation and imaging in a larger number of patients.
authors.affiliation: Department of Nuclear Medicine and PET, PGIMER, Chandigarh, 160012, India.
authors.forename: Pardeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Nuclear Medicine and PET, PGIMER, Chandigarh, 160012, India.
authors.forename: Baljinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Nuclear Medicine and PET, PGIMER, Chandigarh, 160012, India.
authors.forename: Anchal
authors.initials: A
authors.lastname: Ghai
authors.affiliation: Division of Cyclotron and Radiopharmaceuticals Sciences, INMAS, New Delhi, 110054, India.
authors.forename: Puja P
authors.initials: PP
authors.lastname: Hazari
authors.affiliation: Department of Nuclear Medicine and PET, PGIMER, Chandigarh, 160012, India.
authors.forename: B R
authors.initials: BR
authors.lastname: Mittal
authors.affiliation: Division of Cyclotron and Radiopharmaceuticals Sciences, INMAS, New Delhi, 110054, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging*; D004317:Doxorubicin / Q000737:chemistry* / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D011933:Reagent Kits, Diagnostic; D012509:Sarcoma / Q000000981:diagnostic imaging*; D013667:Technetium / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D011933:Reagent Kits, Diagnostic; D013667:Technetium; D004317:Doxorubicin
keywords: [99mTc]-labeled doxorubicin; human use; preclinical evaluation; single vial kit; tumor imaging