99mTc-Labeled (1S,3S)-3-acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-α- l-lyxo-hexopyranoside

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Daunorubicin, a member of the anthracycline family of antibiotics, is approved by the United States Food and Drug Administration (FDA) for the remission induction of acute nonlymphocytic leukemia in adults and for the remission induction of acute lymphocytic leukemia in children and adults. Anthracyclines are known to inhibit cancer cell proliferation by several mechanisms, but it is well established that these antibiotics intercalate between the nucleotides of DNA and RNA and interfere with the replication of these nucleic acids. In addition, anthracyclines inhibit the topoisomerase II group of enzymes that have an important role in DNA replication (2). Doxorubicin, another anthracycline antibiotic with a structure and mechanism of action similar to that of daunorubicin, has been approved by the FDA for the treatment of several types of cancers, such as acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms' tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin's disease, malignant lymphoma, and bronchogenic carcinoma.

Several radiochemicals, such as [^99mTc]-methoxyisobutyl-isonitrile ([^99mTc]-MIBI), [^99m]Tc-tetrofosmin, and [¹⁸F]-fluorodeoxyglucose ([¹⁸F]-FDG), are often used in the clinic with single-photon emission computed tomography (SPECT; for noninvasive imaging with [^99mTc]-MIBI and [^99m]Tc-tetrofosmin) and positron emission tomography (for imaging with [¹⁸F]-FDG) to detect and monitor cancerous tumors. However, these tracers are of limited use for the detection and monitoring of neoplastic lesions because they often generate false-positive results, as detailed elsewhere (3). Transformed cells have a characteristically high proliferation rate and consequently exhibit a higher rate of DNA synthesis compared with the normal cells. Therefore, cells with an elevated rate of DNA synthesis would be expected to intercalate high levels of anthracycline antibiotics within the nucleic acid structure. Based on this assumption, Kumar et al. evaluated the use of ^99mTc-labeled doxorubicin for the noninvasive detection of tumors in mice, and the investigators showed that the tracer was probably suitable for visualization of the lesions with scintigraphy in the rodents (3). Faheem et al. investigated the biodistribution of ^99mTc-labeled daunorubicin ([^99mTc]-daunorubicin) in normal rats, and scintigraphy was used to study the biodistribution of this radiolabeled compound in a rabbit (1). Results obtained from studies performed with [^99mTc]-daunorubicin are presented in this chapter.