Development of a single vial kit formulation of [99mTc]-labeled doxorubicin for tumor imaging and treatment response assessment-preclinical evaluation and preliminary human results

Pardeep Kumar, Baljinder Singh, Anchal Ghai, Puja P. Hazari, B. R. Mittal, Anil K. Mishra

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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. Pre-clinical evaluation of an indigenously developed single vial kit preparation of [99mTc]-doxorubicin indicated that the radiopharmaceutical gets localized in the tumor site in high target to non-target (T/NT) ratio. A significant decline in the T/NT ratio following doxorubicin treatment on follow-up imaging demonstrated that the formulation can be used for treatment response monitoring. Further, use of the radiopharmaceutical in sarcoma patients (limited number) suggested its potential use in differentiating active recurrence from disease remission.

Original languageEnglish (US)
Pages (from-to)242-249
Number of pages8
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume58
Issue number6
DOIs
StatePublished - May 30 2015
Externally publishedYes

Keywords

  • human use
  • preclinical evaluation
  • single vial kit
  • tumor imaging
  • [99mTc]-labeled doxorubicin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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