Radiopharmaceuticals: Nuclear Isotopes for a Noble cause.

priyankamathur35
Nov 24
4 min read

Imagine a medicine that works like a missile. It finds diseased cells and delivers a tiny dose of radiation right where it’s needed. That’s what radiopharmaceuticals do. They are drugs that carry a radioactive atom attached to a molecule that knows how to find a specific target in the body. They could direct the radioactivity to specific cells, tissues, or biological pathways, and are used both to image disease (diagnostic tracers) and to treat disease (therapeutic radiopharmaceuticals).

History of Discovery

The therapeutic potential of radioactivity was recognized shortly after the discovery of radioactivity by Becquerel and the isolation of radium and polonium by Marie and Pierre Curie in the late 19th century. Early uses of radium and X-rays in oncology were non-targeted. The modern era of radiopharmaceuticals began with the development of radiolabelled compounds that localized biologically (e.g., radioiodine-131 for thyroid disease) and progressed to receptor-targeting peptides and small molecules in the late 20th and early 21st centuries.

Principle and Mechanism of Action:

A radiopharmaceutical consists of (1) a radio-isotope that emits detectable radiation and (2) a carrier molecule that directs the isotope to a biological target (for example, glucose analogs, peptides, antibodies). The mechanism of action depends on the role:

Targeting: A biologically active carrier molecule (e.g., peptide, antibody, small molecule) directs the radio-isotope to a specific receptor or metabolic pathway.
Diagnostic action: Radio-isotopes such as ¹⁸F or ⁹⁹ᵐTc emit photons or positrons detected by PET or SPECT scanners. The radioactive atom gives off signals (like tiny beacons) that scanners can detect, creating images of how the body is working.
Therapeutic action: Radio-isotopes such as ¹³¹I, ¹⁷⁷Lu, or ²²⁵Ac emit beta or alpha particles that induce DNA damage and apoptosis in targeted cells, killing them while sparing most healthy tissue.

Radio-isotope types and their radiation biology

Beta (β⁻) emitters (e.g., lutetium-177 (^177Lu), yttrium-90 (^90Y)) produce moderate-energy electrons with tissue ranges of millimetres. β emitters cause DNA single- and double-strand breaks and are suited to treat small to medium-sized lesions and disseminated metastases.
Alpha (α) emitters (e.g., radium-223 (^223Ra), actinium-225 (^225Ac), bismuth-213 (^213Bi)) emit highly energetic, short-range (a few cell diameters) particles that induce dense double-strand DNA breaks, giving high cytotoxicity with steep dose fall-off, advantageous for eradicating isolated tumor cells or micro-metastases.
Auger electron emitters deliver very short-range, high linear energy transfer (LET) damage when localized near DNA. The biological effect depends critically on subcellular localization.

The therapeutic efficacy reflects a combination of radionuclide physical properties (half-life, emission type/energy), radiochemistry stability, targeting vector affinity and biodistribution, and dosimetry.

Why They’re Special

They’re precise and go straight to the target.
They’re personalized, the doctors can test if a tumor takes up the tracer before giving the therapy.
They’re complementary, as they can be combined with surgery, chemo, or external radiation.
Provides functional information beyond anatomical imaging.

Comparison with Other Treatments

Chemotherapy is systemic, non‑specific as it targets all rapidly dividing cells in the body, higher toxicity.
External beam radiotherapy: localized but limited by tumor location, but can cause side-effects.
Radiopharmaceuticals: systemic delivery with molecular precision, often fewer systemic side effects.

Safety and side effects

Common adverse effects reflect off-target radiation to normal tissues (bone marrow, kidneys, salivary glands) and specific toxicity patterns by radio-isotope/type:

Hematologic toxicity: cytopenias (neutropenia, thrombocytopenia, anemia) are the dominant dose-limiting toxicities for many β and α therapies and require monitoring and sometimes dose modification.
Organ-specific toxicity: renal impairment (for renally excreted agents), xerostomia (with PSMA-targeted therapies), gastrointestinal effects, and transient pain flare in metastatic bone disease are reported.
Late effects: secondary myeloid neoplasms have been reported but are uncommon.
Alpha emitters: potent cytotoxicity with high tumoricidal effect but may increase local toxicity if mis-targeted, careful dose and isotope handling is critical.

Landmark Therapies:

Established therapies include: ¹³¹I for thyroid cancer, ¹⁷⁷Lu‑DOTATATE (Lutathera) for gastro-entero-pancreatic neuroendocrine tumors, and Lutetium-177 PSMA-617 (Pluvicto) for metastatic prostate cancer.
Emerging therapies : Alpha‑emitters (²²⁵Ac, ²¹³Bi) for resistant malignancies, that eject pairs of protons and neutrons. it slices the DNA double helix completely, making it harder for repair enzymes to fix the damage.

References:

Abergel R. The Enduring Legacy of Marie Curie: Impacts of Radium in Medicine. Front Oncol. 2022; [historical review].
Strosberg J, El‑Haddad G, Wolin E, et al. Phase 3 trial of ^177Lu‑Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125‑135. doi:10.1056/NEJMoa1607427
Sartor O, de Bono J, Chi KN, et al. Lutetium‑177–PSMA‑617 for metastatic castration‑resistant prostate cancer. N Engl J Med. 2021;385(12):1091‑1103. doi:10.1056/NEJMoa2107322
Herrmann K, Schwaiger M, Lewis JS, et al. Recent advances and impending challenges for the radiopharmaceutical sciences. Lancet Oncol. 2024;25(2):e67‑e78. doi:10.1016/S1470-2045(23)00456-7
Dhoundiyal S, Sharma A, Gupta R, et al. Radiopharmaceuticals: navigating the frontier of precision medicine and therapeutic innovation. Eur J Med Res. 2024;29(1):45. doi:10.1186/s40001-024-01567-2
Chen J, Li Y, Wang H, et al. Radiopharmaceuticals: from discovery to theranostics. J Radioanal Nucl Chem. 2025;331(2):567‑582. doi:10.1007/s10967-025-09876-1
Elliyanti A. Radiopharmaceuticals in modern cancer therapy. In: Advances in Nuclear Medicine. IntechOpen; 2021. doi:10.5772/intechopen.100123

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