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Review
. 2016 Feb 23:3:5.
doi: 10.3389/fmed.2016.00005. eCollection 2016.

Small Molecule Radiopharmaceuticals - A Review of Current Approaches

Shubhra Chaturvedi  1 , Anil K Mishra  1
Affiliations
Review

Small Molecule Radiopharmaceuticals - A Review of Current Approaches

Shubhra Chaturvedi et al. Front Med (Lausanne). .

Abstract

Radiopharmaceuticals are an integral component of nuclear medicine and are widely applied in diagnostics and therapy. Though widely applied, the development of an "ideal" radiopharmaceutical can be challenging. Issues such as specificity, selectivity, sensitivity, and feasible chemistry challenge the design and synthesis of radiopharmaceuticals. Over time, strategies to address the issues have evolved by making use of new technological advances in the fields of biology and chemistry. This review presents the application of few advances in design and synthesis of radiopharmaceuticals. The topics covered are bivalent ligand approach and lipidization as part of design modifications for enhanced selectivity and sensitivity and novel synthetic strategies for optimized chemistry and radiolabeling of radiopharmaceuticals.

Keywords: bioorthogonal approaches; cross-coupling reaction; multivalent ligands; radiopharmaceuticals; surface modification.

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Figures

Figure 1
Figure 1
Binding modes for a ligand (A) monovalent ligand with one receptor unit (B) bivalent ligand with one receptor unit (C) bivalent ligand with receptor dimer.
Figure 2
Figure 2
Comprehensive list of small molecule-based bivalent ligands for diagnostics. (A) 99mTc-DTPA-bis(MPBA), (B) 99mTc-DTPA bis-triazaspirodecanone, (C) 99mTc-MAMA-DGal, (D) 99mTc-Ham, (E) [18F]-MPPSiF, (F) [18F]-bivalent-IA, (G) [18F]-styrylpyridine derivatives, (H) [11C]bivalent β-carbolines, (I) [67Ga]DOTA-MN2, (J) 99mTc-QDDTC-bisbiotin, (K) BMAOI, and (L) bivalent-IA-Cy5.5.
Figure 3
Figure 3
Lipidic modification of the nucleosides for prodrug strategy. (A) [76Br]FBAU 3′,5′-dibenzoate, (B) [18F]-Capecitabine, and (C) pegylated and modified ICF01012.
Figure 4
Figure 4
Lipidic nanoparticles for imaging and enhanced pharmacokinetics. (A) FA targeted pegylated nucleolipids, (B) phospholipid liposomes pegylated targeted against lactoferrin, (C) concept of remote labeling, and (D) squalene-based nanoparticles.
Figure 5
Figure 5
Applications of click chemistry. Structures referenced in (, , –66).
Figure 6
Figure 6
Representative examples for radiopharmaceuticals using SPAAC. Structures referenced in (, , –71, 73, 75, 76).
Figure 7
Figure 7
Selected structures developed using Stille reaction. Structures referenced in (, , –111).
Figure 7
Figure 7
Selected structures developed using Stille reaction. Structures referenced in (, , –111).
Figure 8
Figure 8
Selected structures developed using Suzuki reactions. Structures referenced in (, , , –118).
Figure 9
Figure 9
Selected radiopharmaceuticals developed using Sonogashira coupling. Structures referenced in (, , –120).
Figure 10
Figure 10
Radiopharmaceutical developed using Heck reaction. Structures referenced in (82, 121).
Figure 11
Figure 11
Representative radiopharmaceuticals developed using Misc reactions. Reference: (, , , –129).
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References

    1. Leopoldo M, Lacivita E, Colabufo NA, Niso M, Berardi F, Perrone R. Bivalent ligand approach on 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine: synthesis and binding affinities for 5-HT7 and 5- HT1A receptors. Bioorg Med Chem (2007) 15:5316–21. 10.1016/j.bmc.2007.05.010 - DOI - PubMed
    1. Paolino M, Mennuni L, Giuliani G, Anzini M, Lanza M, Caselli G, et al. Dendrimeric tetravalent ligands for the serotonin-gated ion channel. Chem Commun (2014) 50(62):8582–5. 10.1039/c4cc02502d - DOI - PubMed
    1. Janssen M, Oyen WJ, Massuger LF, Frielink C, Dijkgraaf I, Edwards DS, et al. Comparison of a monomeric and dimeric radiolabeled RGD-peptide for tumor targeting. Cancer Biother Radiopharm (2004) 17(6):641–6. 10.1089/108497802320970244 - DOI - PubMed
    1. Liu S. Radiolabeled multimeric cyclic RGD peptides as integrin αvβ3 targeted radiotracers for tumor imaging. Mol Pharm (2006) 3(5):472–87. 10.1021/mp060049x - DOI - PubMed
    1. Li ZB, Cai W, Cao Q, Chen K, Wu Z, He L, et al. 64Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor αvβ3 integrin expression. J Nucl Med (2007) 48(7):1162–71. 10.2967/JNUMED.107.039859 - DOI - PubMed