Iodine-124: a promising positron emitter for organic PET chemistry

Abstract

The use of radiopharmaceuticals for molecular imaging of biochemical and physiological processes in vivo has evolved into an important diagnostic tool in modern nuclear medicine and medical research. Positron emission tomography (PET) is currently the most sophisticated molecular imaging methodology, mainly due to the unrivalled high sensitivity which allows for the studying of biochemistry in vivo on the molecular level. The most frequently used radionuclides for PET have relatively short half-lives (e.g. 11C: 20.4 min; 18F: 109.8 min) which may limit both the synthesis procedures and the time frame of PET studies. Iodine-124 (124I, t1/2 = 4.2 d) is an alternative long-lived PET radionuclide attracting increasing interest for long term clinical and small animal PET studies. The present review gives a survey on the use of 124I as promising PET radionuclide for molecular imaging. The first part describes the production of 124I. The second part covers basic radiochemistry with 124I focused on the synthesis of 124I-labeled compounds for molecular imaging purposes. The review concludes with a summary and an outlook on the future prospective of using the long-lived positron emitter 124I in the field of organic PET chemistry and molecular imaging.

Scheme 1

[¹²⁴I]MIBG synthesis via Cu(I)-assisted nucleophilic exchange reaction.

Scheme 2

Synthesis of hypoxia imaging agent [¹²⁴I]IAZA.

Scheme 3

Synthesis of hypoxia imaging agent [¹²⁴I]IAZG.

Scheme 4

Synthesis of [¹²⁴I]dRFIB.

Scheme 5

Synthesis of 5-[¹²⁴I]iodo-2’-deoxyuridine ([¹²⁴I]IUdR).

Scheme 6

Synthesis of ¹²⁴I-labeled hypericin.

Scheme 7

Synthesis of [¹²⁴I]FIAU.

Scheme 8

Synthesis of the reference compound m-IPPM and m-[¹²⁴I]IPPM: a) benzene, 0 ºC; b) phenylhydroazonium chloride, 0 ºC, pyridine, room temperature; c) Zn, HOAc/NaOAc, 60 ºC, then reflux; d) Sn₂Me₆, PdCl₂(PPh₃)₂; e) [¹²⁴I]NaI, Iodogen^® beads.

Scheme 9

Synthesis of the reference compound morpholino-IPQA, precursor A and radiolabeling: a) EDC, HCl, DMAP, DMF b) EDC, HCl, HOBt, CH₂Cl₂ c) [¹²⁴I]NaI, NaOH, MeOH, H₂O₂/HOAc (1:3), 1 min vortex, 2 min room temperature.

Scheme 10

Synthesis of ¹²⁴I-labeled EGFR-inhibitors: a) Sn₂Bu₆, Pd(PPh₃)₄, THF; b) [¹²⁴I]NaI, NaOH, HCl, Chloramin T; c) BrCH₂CHCHCOCl; d) Me₂NH; e) ClCH₂COCl; f) MeOCH₂COCl.

Scheme 11

Synthesis of the ¹²⁴I-labeled purpurinimide derivatives [¹²⁴I]12, [¹²⁴I]14 and [¹²⁴I]16: a) (i) n-hexyl amine (ii) HBr/AcOH (iii) 3-Iodobenzyl alcohol; b) (i) 3-iodobenzyl amine (ii) HBr/AcOH (iii) R-OH; c) Sn₂Me₆, PdCl₂(PPh₃)₂; d) Iodogen^®, [¹²⁴I]NaI.

Scheme 12

Synthesis of [¹²⁴I]18: a) Sn₂R₆, Pd(PPh₃)₄, microwave; b) [¹²⁴I]NaI, 30% H₂O₂:HOAc (1:3), 10 min, rt.

Figure 1

Central cannabinoid CB₁ receptor ligand[¹²⁴I]AM281.

Scheme 12

Radiolabeling of the Cdk4/6 inhibitors: a) [¹²⁴I]NaI, Iodogen^®, 5% HOAc in MeOH, DMSO, room temperature, 10 min; b) TFA.

Scheme 13

Synthesis of [¹²⁴I]SHPP and radiolabeling of VG76e: a) [¹²⁴I]NaI, Iodogen^® (pH 6.5); b) VG76e, pH 8.5, 0 ºC.

Figure 2

Structures of 4-[¹²⁴I]SIB and 3-[¹²⁴I]SIB.

Scheme 14

Labeling of Annexin V with 3-[¹²⁴I]SIB.

Scheme 15

Labeling of a peptide/protein with 4-[¹²⁴I]SIB.