By Willie Foerstner

Introduction: What is theranostics?
Theranostics is a fusion of "therapy" and "diagnostics," representing a paradigm shift in precision medicine. The core principle involves using a single molecular targeting agent to diagnose and treat disease simultaneously. This duality allows for real-time tracking of therapeutic delivery, enhanced treatment efficacy, and minimized off-target toxicity. While the term gained popularity in the early 2000s, its scientific roots extend back over a century.

The individual most often referred to as the “father of theranostics” is Dr. Johannes (Hans) Hör of Germany. In the 1990s and early 2000s, Dr. Hör and collaborators formally conceptualized and advanced the dual-use strategy of using the same molecular structure for both imaging and therapy—especially in neuroendocrine tumors and prostate cancer.

However, the foundations were built by many contributors. Here are some of the key pioneers:
• Marie & Pierre Curie (1898–1906): Pioneered the therapeutic use of radium, introducing the notion of targeting disease with radioisotopes.
• Saul Hertz (1941): Used radioactive iodine (I-131) to treat thyroid cancer—considered the first clinical theranostic application.
• Dr. Richard Baum (Germany): Early adopter and evangelist of PSMA theranostics.
• Dr. Johannes Hör: Credited with coining and applying the term “theranostics” in the radiopharmaceutical context.

Origins: The conceptual foundation
• Early 1900s: Marie and Pierre Curie’s discovery of radium and polonium laid the groundwork for targeted radionuclide therapy. Physicians began exploring the effects of radioactive substances on malignant cells. During this period, Bayer—through its pharmaceutical division—played a role in early medicinal chemistry, although its involvement in radiopharmaceuticals wouldn't formalize until the 20th century's second half.
• 1920s-1940s: Radon seeds and radium-226 were used to treat cancers like cervical and prostate cancer—some of the earliest examples of radioisotope-based targeted therapy.
• 1950s-1970s: Nuclear medicine pioneers began using radioiodine (I-131) for both diagnosis and treatment of thyroid diseases, establishing the earliest recognized theranostic application.
• 1980s: Advancements in radiochemistry allowed for more precise labeling of biological molecules like antibodies and peptides with therapeutic radionuclides (e.g., Y-90, Lu-177), laying the groundwork for targeted radiopharmaceuticals.

The rise of molecular imaging and targeted therapy (1990s-2010s)
• 1990s: The advent of PET/CT and SPECT/CT enabled high-resolution, functional imaging of cellular processes. Agents such as FDG (F-18 fluorodeoxyglucose) revolutionized cancer diagnostics.
• 2000s: The development of radiolabeled peptides like Lu-177 DOTATATE and Y-90 ibritumomab marked a significant milestone in treating neuroendocrine tumors and lymphomas, respectively.
• 2010s: PSMA-targeted imaging agents for prostate cancer, such as Ga-68 PSMA-11, catalyzed theranostic pair development with Lu-177 PSMA-617, proving the concept's clinical scalability.

Clinical integration and commercialization (2020s)
• Regulatory Approvals:
o Lu-177 DOTATATE (Lutathera) FDA-approved in 2018 for neuroendocrine tumors.
o Lu-177 PSMA-617 (Pluvicto) FDA-approved in 2022 for metastatic castration-resistant prostate cancer.
• Diagnostic Pairs: Modern theranostics leverage Ga-68 (diagnostic) and Lu-177 or Ac-225 (therapeutic) combinations for highly selective targeting.
• Industry Momentum: Companies like Novartis, Telix, Curium, SOFIE, and Bayer are driving commercial production, global distribution, and clinical trial development. Bayer, through its acquisition of Noria Therapeutics and development of Xofigo (Ra-223), has positioned itself as a key player in radiotherapeutics, particularly in prostate cancer.

Scientific mechanism: How theranostics works
1. Target Identification: Tumor-specific antigens or receptors (e.g., PSMA, somatostatin receptors) are selected.
2. Ligand Design: Peptides, antibodies, or small molecules are engineered to bind with high affinity.
3. Radiolabeling: A radionuclide is attached to the ligand:
o Diagnostic: Ga-68, F-18 (short half-life, positron emission)
o Therapeutic: Lu-177, Ac-225, Y-90 (beta or alpha emitters)
4. Administration: The compound is injected intravenously.
5. Imaging and Treatment: PET/SPECT imaging confirms localization; therapy follows in cases of positive uptake.

Theranostic applications by disease
• Neuroendocrine Tumors (NETs): SSTR imaging with Ga-68 DOTATATE and treatment with Lu-177 DOTATATE
• Prostate Cancer: PSMA PET imaging (e.g., Pylarify®, Illuccix®) paired with Lu-177 or Ac-225 therapy
• Thyroid Cancer: I-131 remains the classic example of a theranostic agent
• Glioblastoma & Brain Tumors: EGFR-targeted radioimmunotherapy in clinical trials
• Breast and Ovarian Cancer: HER2-targeted alpha therapies under investigation

Challenges and limitations
• Supply Chain: Short half-life isotopes require robust local/regional production and distribution.
• Regulatory Complexity: Each tracer must meet strict FDA and international compliance under cGMP and IND/ANDA regulations.
• Reimbursement: Despite CMS pass-through support for some agents, payer variability persists.
• Toxicity Management: Myelosuppression, renal, and salivary toxicity remain concerns, especially with alpha emitters.

Future outlook: The next decade of theranostics
• Alpha Emitters: The rise of targeted alpha therapies (TATs) using Ac-225 and Bi-213 offers high cytotoxicity with limited tissue penetration, ideal for micrometastases.
• Companion AI Imaging: Integration of machine learning for lesion detection, dose planning, and outcome prediction.
• Theranostic CDMOs: Contract Development and Manufacturing Organizations (CDMOs) specialized in GMP tracer production are scaling to support trials and commercialization.
• Expansion into Inflammation and Neurology: Theranostics may extend to diseases like Alzheimer’s, multiple sclerosis, and autoimmune disorders.
• Personalized Dosing Models: Real-time dosimetry and patient-specific biodistribution will refine therapy delivery and safety.

Highlights from SNMMI 2025 Annual Meeting
• Theranostics Takes the Stage: Nearly 7,800 attendees gathered for the “Accelerating the Cure” meeting, showcasing theranostics as a centerpiece of precision medicine across oncology, cardiology, and neurology.
• Novel PET Tracers & Targets:
o Prostatic Acid Phosphatase (ACP3) imaging with 68Ga-OncoACP3 showed promising uptake in prostate cancer, complementing PSMA imaging.
o Image-of-the-Year: 18F-AlF-NOTA-PCP2, a PD-L1 PET tracer that outperformed FDG in head-and-neck cancer.
• Cardiac PET Advances: Study on Flurpiridaz (Flyrcado) PET for myocardial flow reserve in 220 CAD patients received Abstract of the Year.
• Theranostic Therapies in Development:
o Lu-177–labeled FAPI-RGD for dual oncology markers.
o Early use of multiplexed PET—imaging with three tracers simultaneously.
• AI Integration: AI showcased in lesion detection, image reconstruction, and PET quantification.
• Emerging Technologies: Carbon-11 ER176 for neuroinflammation, 18F-PDE-1905 for PDE4B, and Ga-68 GPC3 for hepatocellular carcinoma.
• Systems & Infrastructure: Siemens and GE launched new PET/SPECT systems, theranostic suites, and software platforms like LesionID Pro.
• Multidisciplinary Collaboration: First “Intersection Sessions” unified PET, SPECT, oncology, and nuclear cardiology experts.
• Global Strategy & Access: Sessions on supply resilience, payer engagement, and expanding theranostics to underserved regions.

Conclusion
Theranostics is redefining the way we diagnose and treat cancer and other complex diseases. With expanding clinical validation, stronger reimbursement frameworks, and rapid scientific advancement, theranostics is poised to become a pillar of 21st-century precision medicine. What began as a nuclear medicine curiosity is now a full-scale commercial and clinical frontier, with untapped potential still unfolding in real time.

About the author: Willie Foerstner is healthcare correspondent at PMAC Capital Reports. Willie leverages his unique blend of clinical insight and capital expertise to report on how innovation is funded, developed, validated, and delivered to patients. From advanced imaging technologies—including photon-counting CT, PET/MR, and myocardial perfusion imaging—to cyclotron-based isotope production, theranostics, and next-generation radiopharmaceutical trials, he offers perspective that bridges financial strategies, regulatory pathways, and patient outcomes. With a passion for advancing therapies that aim to eradicate cancer, he is a committed patient advocate whose mission is to align capital with care, highlight how financial and clinical ecosystems must work together to advance precision medicine, and keep the public informed on what is truly cutting edge.

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