Small Molecule Radiopharmaceuticals – A Review of Current Approaches <s> Selectivity through BLA <s> Integrin αvβ3 plays a significant role in tumor angiogenesis and is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic (RGD) tripeptide sequence. These include vitronectin, fibronectin, fibrinogen, lamin, collagen, Von Willibrand's factor, osteoponin, and adenovirus particles. Integrin αvβ3 is expressed at low levels on epithelial cells and mature endothelial cells, but it is overexpressed on the activated endothelial cells of tumor neovasculature and some tumor cells. The highly restricted expression of integrin αvβ3 during tumor growth, invasion, and metastasis presents an interesting molecular target for both early detection and treatment of rapidly growing solid tumors. In the past decade, many radiolabeled linear and cyclic RGD peptide antagonists have been evaluated as the integrin αvβ3 targeted radiotracers. Significant progress has been made on their use for imaging tumors of different origin by single photon emission computed tomography (SPECT) or positron... <s> BIB001 </s> Small Molecule Radiopharmaceuticals – A Review of Current Approaches <s> Selectivity through BLA <s> We here report on the synthesis and binding properties at 5-HT(7) and 5-HT(1A) receptors of ligands 3-12, that were designed according to the 'bivalent ligand' approach. Two moieties of the 5-HT(7)/5-HT(1A) ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1) were linked through their 3-methoxy substituent by polymethylene chains of variable length, with the aim to increase the affinity for 5-HT(7) receptor and the selectivity over 5-HT(1A) receptors. In the best cases, the dimers showed affinities for 5-HT(7) receptors as high as the monomer with no improvement in selectivity. Some dimers displayed 5-HT(1A) receptor affinities slightly higher than monomer 1. <s> BIB002 </s> Small Molecule Radiopharmaceuticals – A Review of Current Approaches <s> Selectivity through BLA <s> Multivalency is widely used in nature in specific recognition processes. This paper describes an approach to multivalency in the pentameric 5-HT3 receptor, a ligand-gated ion channel, which constitutes an example of intrinsically multivalent biological receptors. Owing to the picomolar Ki value, TETRA-L represents an outstanding multivalent ligand for the neurotransmitter receptor. <s> BIB003
Bivalent ligands are examples of multimeric interactions. Multimeric interactions are known to enhance the binding affinity of the ligands through multiple mechanisms, e.g., receptor clustering, chelating effect on receptors, ligand-receptor steric stabilization, and ligand accumulation near the receptor BIB003 . Overall, the effect is enhanced selectivity and enhanced binding affinity BIB002 . The multivalent concept has been extensively validated for peptides. Successful reports for multimeric peptides as diagnostics agent are included in Table 1 . Reviews regarding the development of homo-multimeric and hetero-multimeric peptidic ligands are many, and hence, for peptidic multimeric ligands readers may refer reviews BIB001  . The multimeric concept is now being extended to small molecules as well. Small molecule-based BLs are capable of multimeric interactions, thereby having higher sensitivity and selectivity.