What if doctors could start treating cancer the same moment they found it? With recent developments in theranostics (“therapy” plus “diagnostics”), this “see it, treat it” approach is moving closer to clinical usage. It relies on nuclear medicine, which is transforming healthcare by enabling highly targeted therapies for complex diseases.
While traditionally known for its diagnostic capabilities, nuclear medicine is now advancing into therapeutics through innovations where the same molecular agent is used for imaging and treatment. This shift is redefining how clinicians approach cancer, cardiovascular, and neurological conditions, offering more personalized and effective treatment strategies.
The building blocks of nuclear medicine
At the heart of nuclear medicine therapies are radiopharmaceuticals — compounds that combine radioactive isotopes (radionuclides) with carrier molecules to deliver targeted radiation for either imaging or therapy. These agents are often stabilized by chelators to ensure safe and effective transport within the body (see Figure 1).
Depending on their emission properties, these agents can be used diagnostically in a PET scan (positron emission tomography) and a SPECT scan (single-photon emission computed tomography) or therapeutically to destroy diseased cells by inducing DNA damage. This damage includes single-strand breaks (SSBs) and double-strand breaks (DSBs), with the extent and nature determined by the type of radiation emitted.
Alpha-particle emitters (e.g., radium-223, actinium-225, astatine-211) have high linear energy transfer (LET) and short path lengths, causing dense, localized DSBs that activate apoptotic and pyroptotic pathways. Auger electron emitters (e.g., iodine-125, indium-111) also produce highly localized DSBs due to their short range and high LET.
In contrast, beta-particle emitters (e.g., lutetium-177, yttrium-90) have lower LET and primarily induce indirect DNA damage through the generation of reactive oxygen species (ROS), leading to SSBs or DSBs and oxidative stress. These lesions activate DNA repair mechanisms, such as base excision repair (BER), nucleotide excision repair (NER), non-homologous end joining (NHEJ), and homologous recombination (HR).
However, cancer cells often exhibit impaired DNA repair capabilities, making them vulnerable to radiopharmaceutical-induced cytotoxicity. To enhance therapeutic efficacy, combination strategies involving radiopharmaceuticals and DNA repair inhibitors, such as Poly(ADP-ribose) polymerase (PARP) inhibitors, are being actively explored.
We examined the CAS Content CollectionTM, the largest human-curated repository of scientific information, to better understand the research landscape in nuclear medicine, and we found exponential growth in the volume of publications over the last 20 years. Notably, patent activity surged significantly after 2020, reaching nearly 800 patents by 2024, suggesting increased commercial interest and innovation in nuclear medicine technologies (see Figure 2).
Presently, about 67 radiopharmaceuticals have received FDA approval, comprising 54 diagnostic and 13 therapeutic agents. All currently approved therapeutic radiopharmaceuticals are intended for cancer treatment (see Figure 3).
Among the FDA-approved radiopharmaceuticals, technetium-99m (⁹⁹ᵐTc) is the most used radionuclide for diagnostic imaging, whereas iodine-131 (¹³¹I) remains the leading choice for therapeutic applications. In terms of targeting vectors, small molecules are the most used, owing to their favorable pharmacokinetics and ease of development.
Peptide-based agents have also gained significant clinical relevance, following the FDA approval of [68Ga]/[177Lu]Ga-DOTA-TATE for the diagnosis and treatment of neuroendocrine tumors. Antibody-based radiopharmaceuticals play a crucial role as well, offering high in vivo binding affinity that enhances imaging precision and therapeutic efficacy. Additionally, a smaller group of approved agents includes radiopharmaceuticals based on proteins and serum albumin.
Latest breakthroughs in nuclear medicine
Significant innovations in radiopharmaceuticals, imaging modalities, molecular targeting, and isotope production have driven the evolution of nuclear medicine. In the brief period between 2020-2024, for example, the number of investigational radiopharmaceuticals increased significantly, from around 40 to nearly 170. This rapid expansion is likely driven by regulatory approvals and the commercial success of pioneering agents such as Lutathera® ([177Lu]Lu-DOTA-TATE) for treating neuroendocrine tumors and Pluvicto® ([177Lu]Lu-PSMA-617) for PSMA-positive metastatic prostate cancer, both of which have set new standards in targeted radioligand therapy.
Fields of note include:
- Theranostics: Within this dynamic field, one of the most significant breakthroughs in recent years has been the development of theranostic radiopharmaceuticals, which are similar radiopharmaceutical compounds used for diagnosis and treatment. For example, recently FDA-approved prostate-specific membrane antigen (PSMA) ligands labeled with gallium-68 (Locametz) can be used to detect prostate cancer through PET imaging. The same PSMA ligands, when labeled with lutetium-177, (Pluvicto), can deliver targeted radiation therapy to treat cancer. This approach represents the pinnacle of precision medicine, allowing clinicians to identify disease sites with exceptional accuracy and then deliver radiation therapy directly to those same targets while sparing healthy tissues.
- Targeted alpha therapy: Alpha particles, helium nuclei composed of two protons and two neutrons, exhibit high LET and limited tissue penetration (50–100 μm), making them ideal for delivering lethal radiation doses to individual cancer cells while minimizing damage to surrounding healthy tissue. This property underpins the effectiveness of targeted alpha therapy (TAT), a breakthrough in precision oncology.
Initially exemplified by ²²³Ra-dichloride (Xofigo®), TAT has expanded to include agents like ²²⁵Ac-PSMA-617, which has shown remarkable clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC), with 91% of patients experiencing a decline in prostate-specific antigen (PSA) levels and a median survival of 15 months. Advancements in isotope production now support large-scale manufacturing and the development of novel alpha emitters such as ²¹²Pb. Clinical trials are exploring a range of alpha-emitting therapies across various cancer types, including RayzeBio’s Phase III RYZ101 trial for gastroenteropancreatic neuroendocrine tumors.
Technological innovations are further enhancing TAT’s potential. These include bispecific antibodies, improved conjugation chemistries, and combination strategies with immunotherapies and DNA damage response inhibitors. Together, these developments position TAT as a transformative approach capable of overcoming resistance to traditional beta-emitting radiotherapies.
- Next-generation carriers: Next-generation carrier molecules in nuclear medicine refer to advanced delivery platforms that enhance targeting specificity, pharmacokinetics, and multimodal functionality. Recent research has focused on bicyclic peptides as promising alternatives to traditional carriers, offering antibody-like affinities (nanomolar range) with superior tissue penetration and rapid renal clearance, exemplified by EphA2-targeting BCY18469, which demonstrated high tumor uptake (19.5 ± 3.5 %ID/g at 1 h) and excellent imaging contrast as early as five minutes post-injection.
Ultrasmall nanoparticles (<10 nm) have achieved clinical translation, with Cornell dots in clinical trials for dual PET/optical imaging of different malignancies. The field is advancing toward alternative scaffold proteins including DARPins (designed ankyrin repeat proteins), affibodies, and nanobodies that offer enhanced stability under harsh radiolabeling conditions (up to 95°C, pH 3.6-11.0) while maintaining high target affinity, alongside modular nanotransporters capable of smart, paced delivery to specific cellular compartments.
These innovations address critical challenges in nuclear medicine by reducing off-target toxicity, extending circulation time for optimal tumor accumulation, and enabling the combination of active-passive targeting strategies. They also support the development of theranostic agents that can provide diagnostic imaging and therapeutic intervention within a single platform, positioning next-generation carriers as transformative tools for personalized precision medicine.
- Early-line therapy for early-stage disease: While nuclear medicine has experienced significant clinical growth in recent years, it has traditionally been reserved as a last-resort palliative treatment for advanced cancer patients. This paradigm is now shifting dramatically with active clinical investigations. For example, somatostatin receptor 2 (SSTR2) and PSMA-targeted radiopharmaceutical therapies are showing promise in earlier-stage diseases. Notably, [¹⁷⁷Lu]Lu-DOTA-TATE demonstrated statistically significant and clinically meaningful improvements in progression-free survival when used as initial therapy for advanced gastroenteropancreatic neuroendocrine tumors.
Concurrently, ¹⁷⁷Lu-labeled PSMA-targeted compounds are undergoing extensive clinical testing across multiple prostate cancer scenarios, including treatment-naive metastatic castrate-resistant disease, metastatic hormone-sensitive cancer, oligometastatic or biochemically recurrent disease, and locoregionally advanced or high-risk cases. This expansion from end-stage palliative care to early-line therapeutic intervention represents a fundamental transformation in how radiopharmaceuticals are being integrated into comprehensive cancer treatment strategies, potentially offering patients more effective outcomes when their disease is still in earlier, more treatable stages.
- AI in personalized radiopharmaceutical therapies: AI models facilitate image reconstruction and refinement, automated lesion detection, and organ/tumor identification, enabling personalized dosimetry calculations. This integration aims to make routine and reliable personalization of radiopharmaceutical therapies a reality, enhancing treatment efficacy and patient outcomes.
We can see how these innovations are making their way through the regulatory process and closer to clinical application. Figure 4 categorizes investigational drugs into Phase I, II, and III, with each segment color-coded to represent their intended use: diagnostic, therapeutic, or theranostic. The data reveals that anticancer agents dominate across all phases, particularly in Phase I, which includes 32 drugs. This trend reflects the growing emphasis on targeted radionuclide therapy and theranostics in oncology, aligning with recent literature that highlights the shift toward personalized treatment strategies using radiopharmaceuticals. Other disease areas are also represented, though to a lesser extent, indicating expanding applications beyond cancer.
An analysis of clinical trials underscores the prominence of Gallium-68 (⁶⁸Ga) and Fluorine-18 (¹⁸F) in diagnostic applications, reflecting their widespread use in PET imaging due to favorable half-lives and positron emission properties. In therapeutic applications, Actinium-225 (²²⁵Ac) leads, known for its alpha-emitting properties ideal for targeted radiotherapy. Radionuclides like Copper-64 (⁶⁴Cu) and Lead-212 (²¹²Pb) show dual-use potential, supporting the growing theranostic paradigm that integrates imaging and therapy.
Moving nuclear medicine from concept to the clinic
Bringing nuclear medicine into clinical practice faces several challenges, particularly its high cost and the limited availability of medical isotopes. There is also a lack of trained nuclear medicine professionals and radiopharmacists, as well as infrastructure limitations that restrict access to advanced imaging and therapy. This is most pronounced in lower-income countries.
Expanding stocks of isotopes, growing the workforce, and enhancing access to care are all long-term issues that will take dedicated resources to address. However, the future could be promising given the level of investment and projected growth in this field.
The nuclear medicine sector experienced remarkable growth in 2024, driven by a surge in capital investment and strategic consolidation. According to PitchBook, total investment in the field soared to $14.86 billion, more than tripling the amount invested in 2023. This momentum was further amplified by a wave of high-profile acquisitions as major pharmaceutical companies moved swiftly strengthened their positions in the expanding market, such as AstraZeneca’s $2.4 billion acquisition of Fusion Pharmaceuticals to advance targeted alpha therapies.
Hurdles remain to the wider application of theranostics and nuclear medicine, but more innovations are bringing us ever closer to “see it, treat it” with cancer and other debilitating diseases.
