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

The numbers reported by the research team are striking. Among 49 patients with renal medullary carcinoma who underwent 18F-FDG PET/CT scans at MD Anderson between 2016 and 2025, the radiotracer detected lesions in 98 percent of cases, or 48 of the 49 patients. Even more consequential, in 65 percent of patients the tracer revealed additional cancer lesions that were not visualized on standard anatomical imaging such as computed tomography or magnetic resonance imaging. Those extra findings were not merely academic curiosities: in 21 percent of patients with active disease, the PET/CT results directly changed the clinical management plan, steering physicians away from treatments that would have been futile or harmful and toward strategies better matched to the true extent of disease.

Renal medullary carcinoma is a disease that demands precision from the very first scan. It predominantly affects adolescents and young adults, occurs more often in males, and is strongly associated with sickle cell trait and related hemoglobinopathies, conditions in which the oxygen-carrying environment of the renal medulla appears to create conditions favorable to tumor development. At the time of diagnosis, patients frequently already present with metastatic disease, and the median overall survival is approximately 14.5 months. Against that grim backdrop, every staging decision carries enormous weight. Surgery that might offer curative potential in localized disease becomes a source of suffering and delay when the cancer has in fact spread undetected, because high-morbidity operations postpone the systemic therapies that metastatic patients urgently need.

Simone Krebs, MD, MS, a nuclear medicine physician and scientist at MD Anderson and the study’s lead author, emphasized just how much rides on getting staging right in this disease. In renal medullary carcinoma, she noted, the value of accurate staging cannot be overstated, because upstaging a patient from localized to metastatic disease spares them from noncurative, high-morbidity surgeries that would only delay the initiation of essential systemic therapy. Identifying metastatic disease, she added, may also open opportunities for more effective therapies tailored to a patient’s actual disease burden. Her comments underscore a central tension in oncology: the difference between what imaging shows and what the cancer is actually doing can determine whether a patient receives the right treatment at the right time or loses precious months to the wrong one.

The biological basis for the study’s success lies in the way renal medullary carcinoma handles glucose. 18F-FDG is a glucose analog labeled with fluorine-18; it is taken up by cells through glucose transporters and then becomes metabolically trapped, allowing positron emission tomography to visualize tissues with high glycolytic activity. Many cancers are avid for FDG, but uptake varies considerably across kidney tumor subtypes, which has historically limited the tracer’s reputation in urologic oncology. Clear cell renal cell carcinoma, the most common kidney cancer, often shows variable FDG uptake, and some renal lesions are better characterized by other tracers or by dedicated CT protocols. Renal medullary carcinoma, however, demonstrates strong and consistent FDG uptake, distinguishing it from other kidney cancers and making it an unusually suitable target for FDG PET/CT imaging.

That metabolic avidity translated into practical diagnostic power even in patients who had already begun systemic treatment. The study found that 18F-FDG PET/CT remained highly effective after therapy had been initiated, an important point because treatment can alter tumor metabolism and degrade the performance of metabolic imaging in some cancers. In renal medullary carcinoma, the tracer continued to illuminate active disease, giving oncologists a reliable way to assess how patients were responding and whether residual lesions represented viable tumor. Quantitative PET/CT metrics were evaluated alongside visual interpretation, and the researchers systematically recorded every instance in which imaging findings altered treatment, providing a structured account of the scan’s real-world impact rather than anecdotal impressions.

The clinical consequences of the additional findings were often dramatic. In one illustrative case included in the published work, a patient demonstrated intense focal FDG uptake in nodal, hepatic, soft-tissue, and osseous metastases on maximum-intensity-projection imaging. Axial FDG PET and fused PET/CT images revealed focal intense uptake in the right iliac bone, a finding without a definite correlate on the dedicated CT image. That discrepancy, a metabolically active lesion invisible on anatomical imaging, led directly to changes in the patient’s clinical management. It is precisely this pattern, PET revealing disease that CT cannot confirm, that explains how the tracer upstaged so many patients and redirected so many treatment plans in the study cohort.

For patients, the implications of these findings are potentially life-altering. A young adult with renal medullary carcinoma who appears to have localized disease on a conventional CT scan might, in fact, harbor hepatic, nodal, or bone metastases that only PET/CT can reveal. Detecting those lesions before surgery could spare the patient a major operation that would never have been curative, while simultaneously accelerating access to systemic therapy, the treatment modality most likely to extend survival in metastatic disease. Conversely, for patients whose PET/CT confirms truly limited disease, the scan provides confidence that aggressive local treatment is justified. In both directions, the additional information changes decisions, and in a cancer with a median survival measured in months, better decisions translate directly into better use of the limited time available.

The study’s authors argue that the evidence now justifies a formal change in clinical practice. Their conclusion is that the findings may support the inclusion of 18F-FDG PET/CT in upcoming guidelines regarding renal medullary carcinoma, which would enable broader clinical use beyond specialized centers like MD Anderson. Guideline inclusion matters because renal medullary carcinoma is rare enough that many treating institutions will encounter only a handful of cases, and clinicians may default to conventional staging pathways unless professional society recommendations explicitly endorse metabolic imaging. Krebs and her colleagues contend that PET/CT provides clinically meaningful information beyond conventional imaging, helping doctors better assess the extent of disease and choose the most appropriate treatment strategy, and that on a larger scale the research supports wider adoption in routine patient care.

As molecular imaging continues to expand its role in oncology, the MD Anderson study offers a compelling case study in how an old, proven tool can find new purpose in an underserved disease. 18F-FDG has been a staple of nuclear medicine for decades, yet its value in kidney cancer has been considered limited and subtype-dependent. By rigorously documenting its performance specifically in renal medullary carcinoma, a population of predominantly young patients with few good options, the researchers have turned a routine radiotracer into a potential standard of care for one of oncology’s most aggressive diagnoses. With 98 percent detection, additional lesions found in nearly two-thirds of patients, and management changes in one in five, the case for FDG PET/CT in this disease is difficult to ignore, and the coming updates to clinical guidelines may soon make this powerful scan a routine part of the fight against renal medullary carcinoma.

Subject of Research: Use of 18F-FDG PET/CT imaging for staging and treatment planning in renal medullary carcinoma

Article Title: Proven radiotracer highly effective in detecting rare, aggressive kidney cancer

Article References: Proven radiotracer highly effective in detecting rare, aggressive kidney cancer. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: renal medullary carcinoma, 18F-FDG PET/CT, kidney cancer, molecular imaging, metastatic disease, staging, nuclear medicine, radiotracer, MD Anderson Cancer Center, treatment planning, non-clear cell renal cell carcinoma, Journal of Nuclear Medicine