Emerging Therapeutic Radiopharmaceuticals and Their Theranostic Pairs

Abstract

Nuclear medicine is a rapidly evolving multidisciplinary research field that has been intensively investigated in the past decades. The successful clinical application of various metal‐based radiopharmaceuticals for cancer imaging and therapy is based on the modular assembly of the drug complex through the popular bifunctional chelate (BFC) strategy. In targeted radionuclide therapy (TRT), potent radiation is selectively delivered to the cancer cells using radiopharmaceuticals that incorporate therapeutic radiometals which emit α ‐particles, β − ‐particles, or Meitner–Auger electrons (MAEs). Radiotheranostics is an emerging concept that connects nuclear imaging (via positron emission tomography (PET) or single‐photon emission computed tomography (SPECT)) and therapy for personalized cancer diagnosis and treatment. This article outlines the fundamentals of radiopharmaceutical design and radiotheranostics and presents a general description of the therapeutic emissions accompanied by literature examples of the most promising radionuclides; 212 Pb, 213 Bi, 225 Ac, 227 Th, and 149 Tb for α therapy; 47 Sc, 67 Cu, 77 As, and 161 Tb for β − therapy; and 119 Sb, 135 La, and 197m/g Hg for MAE therapy. A comparison of the currently used or proposed theranostic pairs of each radiometal is presented.

When ring makes the difference: coordination properties of Cu2+/Cu+ complexes with sulfur-pendant polyazamacrocycles for radiopharmaceutical applications

“…2–5 On the other hand, copper-67 ( 67 Cu, t 1/2 61.9 h) is a promising candidate for therapy as well as for single photon emission computed tomography (SPECT) imaging due to its β − ( I β − 100%, E β −,max 141 keV) and γ-rays emission ( E γ 93 keV, I γ 16%; E γ 185 keV, I γ 49%). 6–8…”

Comparative Study of a Decadentate Acyclic Chelate, HOPO-O10, and Its Octadentate Analogue, HOPO-O8, for Radiopharmaceutical Applications

“…The solvents were evaporated under vacuum to obtain 2 as an off-white solid (0.693 g, 70%). 1 H NMR (400 MHz, chloroform-d): δ 9.80 (s, 1H), 7.40−7.28 (m, 5H), 5.15 (s, 1H), 5.08 (s, 2H), 3.49 (q, J = 6.1 Hz, 2H), 2.74 (t, J = 5.8 Hz, 2H). 13 (N1,N4,N9-Tri-tert-butoxycarbonyl)-1,12-diamino-4,9-diazadodecane (3).…”

“…The pure compound was obtained in the form of a yellow oil (2.01 g, 30%). 1 H NMR (600 MHz, methanol-d 4 ): δ 3.37−3.32 (m, 2H), 3.22 (q, J = 6.5 Hz, 6H), 3.03 (t, J = 6.7 Hz, 2H), 2.92 (t, J = 7.2 Hz, 2H), 1.89 (p, J = 7.0 Hz, 2H), 1.74−1.63 (m, 2H), 1.57−1.50 (m, 4H), 1.50−1.39 (m, 27H). 13 Phenylmethyl N- sulfonyl]oxy]propyl]carbamate (4).…”

“…After concentration under reduced pressure, the crude was purified via automated silica gel chromatography (Isolera One, Sfar HC 10 g; gradient A, hexanes; gradient B, ethyl acetate; 0−10 CV, 30% B; 10− 12 CV, 30−100% B) to yield 4 as a colorless oil (1.23 g, 71%). 1 H NMR (400 MHz, chloroform-d 3 ): δ 7.78 (d, J = 8.6 Hz, 2H), 7.40− 7.28 (m, 7H), 5.07 (s, 2H), 4.09 (t, J = 6.0 Hz, 2H), 3.26 (q, J = 6.4 Hz, 2H), 2.43 (s, 3H), 1.93−1.83 (m, 2H). 13 N1,N5,N10-Tri-tert-butoxycarbonyl-N18-benzyloxycarbonyl-1,5,10,14,18-pentaazaoctadecane (5).…”

“…Radiotheranostics is an emerging concept in nuclear medicine that describes the use of radionuclides for the therapy and diagnosis of disease. In nuclear oncology, radionuclides are specifically delivered to the tumor site through a drug complex known as a radiopharmaceutical, which generally consists of four parts: radioisotope, bifunctional chelate (BFC), linker, and targeting vector (e.g., antibody or peptide). , To achieve the ultimate goal of a highly specific and personalized cancer treatment, the radiopharmaceuticals used for therapy and imaging applications should have identical molecular structures, resulting in identical or very similar biodistributions to ensure that radioactive uptake of the imaging drug accurately depicts uptake of the therapeutic pharmaceutical; for this purpose, the use of identical or chemically very similar isotope pairs is desired to ensure that this requirement is met . The diagnostic radiopharmaceutical will emit photons (either directly or indirectly) for imaging using single-photon emission computed tomography (SPECT) or positron emission tomography (PET), and the therapeutic construct will emit particulate radiation [α or β – particles or Meitner–Auger electrons (MAEs)] to produce irreparable cell damage and eradicate the tumor.…”