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Review

99mTc-Labeled doxorubicin

Liang Shan  1
In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004.
[updated ].
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Review

99mTc-Labeled doxorubicin

Liang Shan.
Free Books & Documents

Excerpt

Molecular imaging is considered to be a decision-making tool throughout the drug discovery and initial stages of clinical trials (1, 2). Molecular imaging techniques have been used to validate the potential drug targets, determine the drug pharmacokinetics and biodistribution, and assess the drug–target interaction (3). One notable example is the phase 0 clinical trial, which has been developed in response to the exploratory Investigational New Drug (IND) guidance of the United States Food and Drug Administration (1, 4). Phase 0 clinical trials perform first-in-human testing of IND drugs at microdoses (<100 ug) and allow the demonstration of drug–target effects and assessment of pharmacokinetic–pharmacodynamic relationships in humans earlier in clinical development (2, 3). Phase 0 trials are expected to reduce the high failure rate of new drug candidates in clinical trials and to decrease the prolonged timeline and high cost due to the low predictability of toxicity and efficacy with traditional preclinical studies. The drug and target information in these studies is obtained by directly labeling the drugs themselves and/or by imaging the drug targets with specific molecular probes. On the other hand, some well-studied, clinically used drugs have been explored as molecular imaging agents for tumor detection and other purposes. These studies take advantage of the fact that these drugs are already well understood in terms of their targeting, pharmacokinetics, toxicity, and other characteristics. Examples include the studies performed by Kumar et al., who tested the feasibility of doxorubicin as an imaging agent for tumor detection (5).

Doxorubicin is a well-investigated anthracycline antibiotic and widely used in cancer chemotherapy (6). The planar aromatic chromophore portion of doxorubicin intercalates between two base pairs of DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with the flanking base pairs immediately adjacent to the intercalation site (6, 7). The doxorubicin–DNA intercalation inhibits the progression of the enzyme topoisomerase II and stabilizes the topoisomerase II complex after it breaks the DNA chain; this prevents the DNA double helix from being resealed and thereby stops the process of replication. It is estimated that several thousand doxorubicin analogs have been synthesized (8). This chapter summarizes the data obtained in studies of 99mTc-doxorubicin performed by Kumar et al. (5).

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