Metallic radionuclides in the development of diagnostic and therapeutic radiopharmaceuticals

Abstract

Metallic radionuclides are the mainstay of both diagnostic and therapeutic radiopharmaceuticals. Therapeutic nuclear medicine is less advanced but has tremendous potential if the radionuclide is accurately targeted. Great interest exists in the field of inorganic chemistry for developing target specific radiopharmaceuticals based on radiometals for non-invasive disease detection and cancer radiotherapy. This perspective will focus on the nuclear properties of a few important radiometals and their recent applications to developing radiopharmaceuticals for imaging and therapy. Other topics for discussion will include imaging techniques, radiotherapy, analytical techniques, and radiation safety. The ultimate goal of this perspective is to introduce inorganic chemists to the field of nuclear medicine and radiopharmaceutical development, where many applications of fundamental inorganic chemistry can be found.

Fig. 1

Schematic representation of PET imaging technique.

Fig. 2

Radiopharmaceutical design: schematic diagram of the bifunc-tional chelator (BFC) approach and different bioconjugation strategies. R is the chelator part of the BFC.

Fig. 3

Radiopharmaceutical design: an example of an integrated approach.

Fig. 4

Selected BFCs often employed in conjugate labeling strategies.

Fig. 5

Selected diagnostic radiopharmaceuticals based on small metal complexes.

Fig. 6

Common technetium core structures (BM is the targeting biomolecule).

Fig. 7

Examples of some ionic and neutral [Tc(CO)₃]⁺ core complexes. The R group may be a biomolecule or a linker attached to the biomolecule.

Fig. 8

(A) An example of commercially available ⁶⁸ Ga-generators (Courtesy of Y. M. Daltorio, E & Z, Germany); (B) Somatostatin analogue ⁶⁸Ga–DOTA–TOC.

Fig. 9

Structure of Cu–ATSM and Cu–PTSM (Cu = ⁶²Cu or ⁶⁴Cu).

Fig. 10

Structure of TETA, CB–TE2A conjugates with Tyr³–Octreotate.

Fig. 11

MicroPET projection images of AR42J tumor bearing rats at 4 h after injection (A); liver, kidney (B); and tumor (C) showing the ⁶⁴Cu activity uptake at 1, 4, and 24 h post-injection. This image is reprinted with the permission from American Association for Cancer Research: Sprague et al., Clin. Canc. Res., 2004, 10, 8674.

Fig. 12

Copper complex of sarcophagine-based cage-like BFC and an ORTEP representation shows a distorted octahedral structure with axial Jahn–Teller elongation (Ma et al. Chem. Commun. 2009, 22, 3237; reproduced by the permission of the Royal Society of Chemistry).

Fig. 13

Structure of ⁸⁹Zr labelled desferrioxamine conjugate with mAb.

Fig. 14

Immuno-PET images with ⁸⁹Zr–cmAb U36 of a head and neck cancer patient with a tumor in left tonsil (large arrow) and lymph node metastases (small arrows). Images were obtained 72 h post-injection. A, sagittal image; B, axial image; and C, coronal image. This image is reprinted with the permission from American Association for Cancer Research: Bo¨rjesson et al., Clin. Canc. Res., 2006, 12, 2133.

Fig. 15

Structures of some therapeutic radiopharmaceuticals. A: ¹⁵³Sm–EDTMP (Quadramet); B: ¹⁷⁷Lu and ⁹⁰Y-labelled DOTATOC, a somatostatin analog useful for tumor imaging and therapy.