Harnessing the power of radiopharmaceuticals and theranostics for precision cancer diagnosis and treatment
When Sarah was diagnosed with an advanced neuroendocrine tumor, her treatment options were limited. Then her doctors proposed a revolutionary approach: they would use a radioactive compound to first locate every cancer cell in her body, then deliver a targeted radiation payload to destroy those same cells while sparing her healthy tissue. This "see it, treat it" approach represents a breakthrough in cancer care that's extending lives and offering new hope to patients like Sarah 5 .
Welcome to the world of nuclear oncology—a rapidly advancing field where radioactive drugs are transforming how we diagnose and treat cancer. By harnessing the power of atomic physics and molecular biology, nuclear oncology allows physicians to attack cancer with what one expert calls "guided missiles" that seek out and destroy tumor cells with unprecedented precision 3 .
The field is experiencing explosive growth, with investment soaring to $14.86 billion in 2024—more than triple the amount invested just a year before 5 . What makes this approach unique is the concept of theranostics—using nearly identical radioactive compounds for both diagnosis and therapy, enabling truly personalized cancer treatment 5 .
| Year | Development | Significance |
|---|---|---|
| 2021 | First KRAS inhibitor approved | Began targeting "undruggable" cancer mutations 2 |
| 2022 | Lutathera® for neuroendocrine tumors | Established new standard for targeted radioligand therapy 5 |
| 2024 | Pluvicto® for PSMA-positive prostate cancer | Proven effective for metastatic castration-resistant prostate cancer 5 |
| 2025 | 225Ac-SSO110 entering Phase 1/2 trials | First SSTR2-targeting antagonist with Actinium-225 for small cell lung cancer 6 |
At the heart of nuclear oncology are radiopharmaceuticals—sophisticated drugs consisting of two key components: a radioactive isotope that either emits detectable signals for imaging or destructive energy for therapy, and a targeting molecule that seeks out specific proteins on cancer cells 5 . Think of them as specialized delivery trucks carrying either surveillance equipment (for diagnosis) or weapons (for treatment) directly to enemy territory (cancer cells).
The targeting component is what makes this approach so precise. Different carriers—including peptides, antibodies, and small molecules—are engineered to recognize and bind to specific receptors abundant on cancer cells, such as PSMA in prostate cancer or SSTR2 in neuroendocrine tumors and some lung cancers 5 6 .
Emits signals for imaging or energy for therapy
Seeks out specific proteins on cancer cells
The true power of modern nuclear oncology lies in theranostics (therapy + diagnostics). This approach uses two nearly identical compounds: one for diagnosis and one for therapy 5 . For example:
This "see it, treat it" method represents the pinnacle of precision medicine, allowing clinicians to confirm the presence of the right target before initiating treatment 5 .
Nuclear oncology employs different types of radiation depending on the clinical goal. Diagnostic radiopharmaceuticals use low-energy emissions that are easily detected by imaging equipment but cause minimal cellular damage. Therapeutic radiopharmaceuticals deliver higher-energy particles that damage cancer cell DNA, leading to cell death 7 .
Common Isotopes: Gallium-68, Fluorine-18
Primary Use: Diagnosis (PET)
Emits signals detectable by PET scanners 7
Common Isotopes: Technetium-99m
Primary Use: Diagnosis (SPECT)
Creates images using gamma cameras 7
Common Isotopes: Lutetium-177, Yttrium-90
Primary Use: Therapy
Causes DNA damage through reactive oxygen species 5
Common Isotopes: Actinium-225, Radium-223
Primary Use: Therapy
Causes dense, localized DNA damage with high energy 5
Recent preclinical research highlights the remarkable potential of targeted alpha therapy. In a study presented at the 2025 European Association of Nuclear Medicine Congress, scientists investigated a new compound called 225Ac-SSO110 for treating extensive-stage small cell lung cancer (ES-SCLC) and Merkel cell carcinoma 6 .
This experiment is particularly significant because small cell lung cancer is highly aggressive and can quickly become treatment-resistant. Researchers believe radiopharmaceuticals could offer a powerful new way to treat this disease by making cancer cells more susceptible to immunotherapy 2 .
Developed SSO110, a somatostatin receptor 2 (SSTR2) antagonist that binds to SSTR2 receptors commonly found on certain lung cancer and neuroendocrine cells without being absorbed into the cell 6
Labeled SSO110 with Actinium-225, a powerful alpha-emitting isotope 6
Compared 225Ac-SSO110 against an existing compound (225Ac-DOTA-TATE) in mouse models with SCLC xenografts 6
Tracked the distribution of Actinium-225 and its decay product, Bismuth-213, in various tissues 6
Measured tumor uptake, retention time, and treatment efficacy between the two compounds 6
Monitored for potential side effects and histopathological abnormalities 6
The findings were promising and could signal a major advance in targeted alpha therapy:
| Parameter | 225Ac-SSO110 | 225Ac-DOTA-TATE | Significance |
|---|---|---|---|
| Tumor uptake | Superior | Moderate | Better accumulation at cancer site 6 |
| Tumor retention | Enhanced | Standard | Longer exposure to radiation 6 |
| Daughter redistribution | Minimal | Comparable | Reduced risk of off-target damage 6 |
| Tumor growth control | Complete remission after single 30 kBq injection | Failed to control tumor growth at same dose | Significant efficacy improvement 6 |
| Treatment safety | Well-tolerated, no abnormalities | Well-tolerated | Favorable safety profile 6 |
The most remarkable finding was that 225Ac-SSO110 achieved complete tumor remissions after just a single injection, while the comparison compound failed to control tumor growth at the same radiation dose 6 . This suggests that the unique non-internalizing binding property of SSO110—it remains on the cell surface rather than entering the cell—contributes to its enhanced effectiveness.
Why are alpha emitters like Actinium-225 so effective? Alpha particles are helium nuclei composed of two protons and two neutrons that deliver exceptionally high energy over extremely short distances (50-100 micrometers)—roughly the width of a human hair 5 . This means they can deliver lethal radiation doses to individual cancer cells while minimizing damage to surrounding healthy tissue 5 .
The 225Ac-SSO110 compound also demonstrated minimal redistribution of its radioactive daughter isotopes, particularly Bismuth-213, which is critical for safety as it reduces the risk of radiation damage to healthy tissues 6 .
2 protons + 2 neutrons
Lethal to cancer cells
50-100 micrometers
Behind these clinical advances lies a sophisticated array of research tools that enable scientists to develop and test new radiopharmaceuticals.
Investigate protein phosphorylation status. Used for studying cancer-related signaling pathways in kinases 4 .
Create 3D cell culture environments. Used for gel droplet-embedded culture drug sensitivity tests 4 .
Enable spheroid/organoid formation. Used for drug screening using 3D cancer models 4 .
Safely bind metallic radionuclides to targeting molecules. Used for creating radiopharmaceuticals like [68Ga]Ga-DOTA-TATE 7 .
Detect specific cancer biomarkers. Used for research on plasminogen activation system in tumor malignancy 4 .
Next-generation targeting molecules. Used for EphA2-targeting BCY18469 with high tumor uptake 5 .
These tools have been instrumental in advancing the field. For instance, PrimeSurface® culture ware features a unique ultra-hydrophilic coating that prevents chemical elution and promotes spontaneous spheroid formation, allowing researchers to create more accurate 3D tumor models for drug testing 4 .
Meanwhile, Phos-tag™ products help scientists investigate phosphorylation cascades in various kinases—critical research since many modern cancer drugs target these pathways 4 .
The integration of artificial intelligence is taking nuclear oncology to new levels of precision. AI models now facilitate image reconstruction, automated lesion detection, and organ/tumor identification, enabling personalized dosimetry calculations 5 . This means doctors can tailor radiation doses to individual patients based on precise predictions of how the treatment will behave in their specific anatomy.
AI is also revolutionizing clinical trials in nuclear oncology. Platforms like HopeLLM help physicians summarize patient histories, identify trial matches, and extract data for research—streamlining the process of bringing new radiopharmaceuticals to patients 3 .
Perhaps the most significant shift in nuclear oncology is its movement from end-stage palliative care to early-line therapeutic intervention 5 . Radiopharmaceuticals that previously were used only when all other options had failed are now being tested in earlier disease stages with remarkable success.
177Lu-labeled PSMA-targeted compounds are undergoing extensive clinical testing across multiple prostate cancer scenarios, including:
[177Lu]Lu-DOTA-TATE has demonstrated statistically significant improvements in progression-free survival when used as:
As nuclear oncology advances, the field is developing specialized approaches to clinical trials. Radiopharmaceutical studies introduce unique demands on protocol development, requiring careful consideration of isotope half-life, dosimetry planning, and radiation safety compliance 8 .
"Radiopharmaceutical trials introduce operational intricacies that many Sponsors underestimate, including site infrastructure, regulatory variance, and radioactive material handling," explains Deb Hirscher, Senior Director of Clinical Trial Management at Medpace 8 .
Successfully navigating these complexities requires collaboration across clinical operations, regulatory teams, and imaging experts—a challenge that specialized research organizations are now addressing 8 .
Nuclear oncology represents a fundamental shift in our approach to cancer treatment—from carpet-bombing the body with chemotherapy to sending precision-guided missiles directly to cancer cells. The field is advancing at an astonishing pace, driven by innovations in theranostics, alpha therapy, and artificial intelligence.
While challenges remain—including high costs, limited isotope availability, and the need for specialized medical training—the future appears bright 5 . With massive investment fueling research and development, and with clinical trials increasingly demonstrating success in earlier-stage disease, nuclear oncology is poised to become an integral component of comprehensive cancer care.
As Dr. Germo Gericke, Chief Medical Officer of Ariceum Therapeutics, noted regarding their targeted alpha therapy program: "With initial safety readout expected in 2026 and preliminary efficacy in 2027, we remain committed to setting new standards in both research and patient care for diseases with high unmet needs" 6 . For patients facing cancers that were once considered untreatable, these advances offer more than just extended survival—they offer hope.