Theranostics Comes of Age: New Supplement Maps the Field’s Next Decade

Theranostics, the pairing of a diagnostic imaging agent with a therapeutic radiopharmaceutical targeting the same molecular marker, has moved decisively from experimental concept to established cancer treatment modality. That maturation is now being formally take stock of in a new supplement to The Journal of Nuclear Medicine titled Theranostics: The State of the Art, guest edited by Ken Herrmann, MD, MBA, together with JNM Editor-in-Chief Johannes Czernin, MD. The supplement assembles leading voices in nuclear medicine and oncology to map where the field stands today and, more importantly, where it must go next if it is to convert recent clinical wins into durable, widespread standards of care.

The scale of the current moment is captured by Czernin’s assessment that nuclear medicine is in the middle of a renaissance measurable in both scientific output and financial sustainability. That claim is not mere enthusiasm. Over the past decade, radioligand therapies targeting prostate-specific membrane antigen in prostate cancer and somatostatin receptors in neuroendocrine tumors have delivered survival benefits in pivotal trials, prompting regulatory approvals and triggering substantial industrial investment. The supplement reflects that shift across its entire breadth, covering radionuclide production and supply chains, personalized dosimetry, combination therapies, and the phase 3 trials expected to define the field’s next approved indications.

Yet the supplement is also candid about structural imbalances that could constrain growth. As Czernin observes, science is expanding faster than isotope production capacity, production capacity is expanding faster than dosimetric standardization, and clinical adoption is expanding faster than the trained workforce. In other words, each link in the theranostics chain is lagging behind the one before it, and the weakest links now sit in manufacturing, standardization, and manpower rather than in basic discovery. Industry, he notes, has recognized the opportunity and is funding it accordingly; the remaining burden falls on academic nuclear medicine to keep pace on evidence, personalization, and training.

One of the most technically consequential contributions examines the expanding therapeutic toolbox of emerging isotopes. Cindy Rodriguez, Grace K. Liles, Suzanne E. Lapi, and Jason S. Lewis break down which radionuclides can and cannot be produced at scale today. The distinction matters enormously at the bedside. Alpha-emitting isotopes such as actinium-225 deliver dense, double-strand DNA-breaking radiation over very short path lengths, making them attractive for precise tumor killing, but their global supply remains scarce and production routes are complex. Beta emitters such as lutetium-177 are easier to produce and already anchor approved therapies, while terbium-149, astatine-211, and lead-212 each present distinct chemistry, logistics, and dosimetry challenges that determine whether laboratory promise can ever reach routine clinical use.

Richard Zimmermann’s contribution on the supply chain sharpens that point with a provocative thesis: economics, not science, will decide which radionuclides make it to market. A radionuclide with elegant physics and favorable radiobiology is clinically irrelevant if reactor irradiation capacity, target material availability, generator networks, and reimbursement cannot sustain reliable delivery to hospitals. The supplement’s treatment of this conundrum underscores a reality often obscured by headline trial results: theranostics is as much an industrial logistics problem as a molecular one, and investors, manufacturers, and health systems must align before patients benefit at scale.

Clinical strategy is addressed through two complementary reviews. Yang Wang, Jane McKenzie, and Shahneen Sandhu survey radiopharmaceutical combination therapies in advanced prostate cancer, cataloging trials that pair radioligands with androgen receptor pathway inhibitors, chemotherapy, immunotherapy, and DNA damage response targeting in an effort to overcome monotherapy resistance. Meanwhile, Evan R. Abt, Caius G. Radu, Johannes Czernin, and Christine E. Mona dissect the biology of tumor resistance to radiopharmaceutical therapy itself, examining mechanisms such as heterogeneous target expression, impaired DNA repair pathways, and tumor microenvironmental factors that allow surviving clones to repopulate after treatment. Understanding these mechanisms is the prerequisite for rational combination design rather than empiric trial-and-error.

The phase 3 landscape receives its own detailed mapping from Wolfgang P. Fendler, Michael S. Hofman, David Kersting, Jeremie Calais, and Thomas A. Hope, who chart anticipated future indications across a remarkable slate of trials including PSMAcTION, STAMPEDE2, PSMA-DC, PSMAddition, NETTER-3, ACTION-1, and COMPOSE. These studies extend radioligand therapy into earlier disease stages, combine it with established systemic agents, and test novel targets and isotopes. Their results over the coming years will determine whether theranostics remains a late-line option for advanced disease or becomes embedded earlier in treatment algorithms for prostate cancer, neuroendocrine tumors, and potentially other malignancies.

Personalization is the field’s other great frontier. Richard L. Wahl and Yuni K. Dewaraja examine the evidence for dosimetry-driven personalization of radiopharmaceutical therapies, asking whether patient-specific absorbed dose calculations can and should replace the one-size-fits-all activity prescriptions that dominate current practice. Radiopharmaceutical therapy is unique among cancer treatments in that the therapeutic agent can be imaged directly as it distributes through the body, offering a built-in pharmacokinetic readout. Realizing that advantage requires standardized quantitative imaging, validated dose-response models, and clinical trial designs that test adaptive dosing, all of which remain works in progress despite growing enthusiasm.

Finally, the supplement confronts the human infrastructure problem. Martin Gotthardt, Hossein Jadvar, and David Mankoff argue for a dedicated nuclear oncology subspecialty with tailored training paths, contending that physicians must be fluent simultaneously in radionuclide therapy, molecular imaging, and systemic oncology. Boris Hadaschik and Oliver Sartor examine whether uro-oncologists have embraced nuclear medicine as a true partner in cancer therapy, a question of interdisciplinary trust that will shape referral patterns for years. Caner Civan, Wolfgang P. Fendler, Alina Küper, Lisa Bodei, Wolfgang A. Weber, Louise Emmett, and Ken Herrmann close the volume by taking stock of the field overall and looking ahead to emerging indications. Taken together, the supplement portrays a discipline at an inflection point: scientifically validated, commercially backed, and clinically expanding, but racing to build the isotope supply, dosimetric standards, and specialist workforce its own success now demands. The full supplement is available from The Journal of Nuclear Medicine, with publication support acknowledged from Novartis, Siemens, RayzeBio, and AstraZeneca.

Subject of Research: Current state and future directions of cancer theranostics, including radiopharmaceutical development, dosimetry, clinical trials, and workforce training

Article Title: What’s next for theranostics?

Article References: What’s next for theranostics?. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: theranostics, radiopharmaceuticals, nuclear medicine, radionuclide therapy, dosimetry, prostate cancer, neuroendocrine tumors, phase 3 trials, isotope production, tumor resistance, nuclear oncology, Journal of Nuclear Medicine