64Cu-{ N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(aminomethyl)pyridine}

Excerpt

Chemokine receptors are G-protein–coupled receptors that direct cell movement (when activated by a ligand) toward higher concentrations of chemokines. Chemokine receptor 4 (CXCR4) and its ligand, stromal cell–derived factor-1 (SDF-1 or CXCL12), are known to play a major role in the migration of progenitor cells during embryonic development of the central nervous, cardiovascular, and hematopoietic systems (1, 2). In addition, this CXCR4/SDF-1 receptor system has a function in the development, progression, and spread of various cancers (3), and the CXCR4 acts as a co-receptor for human immunodeficiency virus (HIV) on CD4⁺ T cells (4). It has also been suggested that CXCR4/SDF-1 interaction participates in the pathogenesis of neurodegenerative and inflammatory conditions (5). CXCR4 is expressed by many different types of cancers, and overexpression of CXCR4 in cancers indicates poor prognosis with aggressive and metastatic tumors and resistance to chemotherapy (6).

CXCR4 is considered to play an important role in HIV infections and cancers (4). It is critical to perform imaging studies to measure CXCR4 levels under in vivo conditions for various pathological and physiological conditions (7). ^99mTc-SDF-1 has been used with single-photon emission computed tomography (SPECT) to determine changes in CXCR4 expression in the heart after a myocardial infarction. ⁶⁴Cu-1,1'-[1,4-Phenylenebis(methylene)]-bis[1,4,8,11-tetraazacyclotetradecane] (⁶⁴Cu-AMD3100), a bicyclam inhibitor of CXCR4 activity, has been studied in mice bearing orthotopic breast tumors and in mice with lung metastases with positron emission tomography (PET) (8). {N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(aminomethyl)pyridine} (AMD3465) is a monocyclam CXCR4 inhibitor with a ~15-fold higher affinity for CXCR4 than AMD3100. De Silva et al. (9) radiolabeled AMD3465 with ⁶⁴Cu to form ⁶⁴Cu-AMD3465 for PET imaging of CXCR4 expression in xenograft tumors in mice.