Tracer Debate: Fluorinated MIBG Alternative Sparks Scientific Exchange in Neuroblastoma Imaging

A quiet but consequential dispute is unfolding in the pages of Pediatric Radiology, and it centers on one of the most important questions in pediatric oncology imaging: how best to see neuroblastoma, the most common extracranial solid tumor of childhood. In a Matters Arising item published on 31 August 2026, nuclear medicine physicians Domenico Albano of the University of Brescia and Giorgio Treglia of Ospedale Regionale di Bellinzona e Valli and the University of Lausanne respond to a critique from colleagues at Memorial Sloan Kettering Cancer Center concerning the comparative value of two molecular imaging tracers. The exchange may read like academic housekeeping, but it touches on a technology decision that could reshape staging, treatment planning, and ultimately outcomes for children with a disease that remains one of the most stubborn challenges in pediatric cancer medicine.

At the heart of the debate is metaiodobenzylguanidine, known almost universally in the field as MIBG. For roughly four decades, radiolabeled MIBG has been the workhorse of neuroblastoma imaging. The molecule is a norepinephrine analog that is taken up by cells expressing the norepinephrine transporter, a protein abundantly displayed on neuroblastoma cells. When labeled with iodine-123, a gamma-emitting radionuclide, MIBG allows physicians to map tumor deposits across the body using single-photon emission computed tomography, or SPECT. The same biology underpins a second use: when labeled with iodine-131, a beta-emitting isotope, MIBG becomes both a diagnostic probe and a therapeutic agent, delivering targeted radiation to tumor cells that absorb it. This dual identity makes MIBG unusually important, because the tracer used to find the disease is also the tracer used to treat it.

The challenger in this story is a fluorinated cousin of MIBG called 18F-metafluorobenzylguanidine, abbreviated mFBG. Chemically, the two molecules are close relatives: both are guanidine derivatives that hijack the norepinephrine transporter to accumulate inside neuroendocrine and neuroblastoma cells. The critical difference lies in the radioactive label. Fluorine-18 is a positron emitter, which means it enables imaging with positron emission tomography rather than SPECT. PET detectors register the annihilation photons produced when positrons meet electrons, yielding images with substantially higher spatial resolution, better contrast, and more accurate quantification than conventional gamma-camera imaging. Fluorine-18 also has a physical half-life of about 110 minutes, compared with roughly 13 hours for iodine-123, which affects logistics, radiation dosimetry, and the practicalities of distribution to hospitals without an on-site cyclotron.

The case for mFBG gained momentum through a series of clinical studies. A first-in-human biodistribution and dosimetry study published in the Journal of Nuclear Medicine in 2018 by Nadia Pandit-Taskar and colleagues evaluated 18F-meta-fluorobenzylguanidine in patients with neuroendocrine malignancies and established its safety profile and radiation dose characteristics. More recently, in 2025, the same group published a lesion-based analysis of mFBG PET imaging specifically in neuroblastoma, examining how the tracer performs at the level of individual tumor deposits. These investigations suggested that the fluorinated agent could detect disease with a sensitivity and image quality that might rival or exceed the established iodine-123 compound, while offering the quantification advantages inherent to PET.

Against this backdrop, Albano, Bertagna, Piccardo, Fiz, and Treglia published a systematic review and meta-analysis in Pediatric Radiology in 2026 that directly compared 18F-mFBG with 123I-MIBG in neuroblastoma. Meta-analysis is a statistical technique that pools the results of multiple independent studies to extract a more precise estimate of a diagnostic test’s performance than any single trial can provide. Their head-to-head synthesis, drawing on the accumulated published evidence, represented one of the first attempts to formally quantify whether the new fluorinated tracer truly outperforms the old guard. The work quickly became a reference point in the field, and, as is often the case when a new technology threatens to displace an entrenched standard, it did not go unchallenged.

The challenge came from Yadgarov, Antonevskaya, and Likar, whose reply, published on 17 August 2026, took issue with aspects of the meta-analysis and with the broader inference that mFBG PET/CT is ready to supplant MIBG scintigraphy in routine clinical practice. Their critique, and the response from Albano and Treglia published two weeks later, exemplifies a familiar pattern in diagnostic imaging research. When a new tracer with superior physics arrives, enthusiasm can outrun the evidence. Questions that matter in this transition include whether the studies being compared enrolled comparable patient populations, whether the reference standards used to confirm true disease status were equivalent, whether lesion detection rates were analyzed per patient or per lesion, and whether the dosimetric implications of switching tracers have been fully characterized in children rather than extrapolated from adult neuroendocrine tumor cohorts.

These methodological points are not pedantic. In pediatric neuroblastoma, imaging findings directly determine risk stratification and therapy. The International Neuroblastoma Risk Group staging system and the treatment protocols built upon it rely on MIBG avidity as a defining biological feature of the disease. A child whose tumor takes up MIBG is eligible for 131I-MIBG targeted radiotherapy if standard treatment fails; a tumor that is MIBG-negative generally is not. If mFBG were to replace MIBG for diagnostic imaging, the field would need to confirm that the new tracer identifies the same transporter-expressing cell population, so that diagnostic avidity continues to predict therapeutic avidity. A tracer that lights up more lesions on a prettier image is not automatically a better tracer if it changes the relationship between what is seen and what can be treated.

The dosimetry question adds another layer of complexity, particularly acute in pediatrics. Children are more radiosensitive than adults, and every imaging examination must be justified against the radiation burden it imposes. Fluorine-18’s short half-life means the administered activity clears quickly, which can reduce the effective dose compared with longer-lived isotopes, but the full-body biodistribution of mFBG in children, including uptake in organs such as the myocardium, liver, and salivary glands, must be mapped carefully. The 2018 first-in-human study provided adult dosimetry data, and the 2025 lesion analysis extended the clinical picture, but pediatric-specific dosimetry remains an area where reviewers and regulators rightly demand rigor. Any claim that one tracer is safer than another must rest on measured dose coefficients in the population actually being imaged, not on assumptions carried across age groups and disease types.

There is also a practical economics dimension that the scientific exchange implicitly raises. Iodine-123 MIBG is available through established radiopharmacy supply chains in many countries, whereas 18F-mFBG requires either a local cyclotron and radiochemistry capability or a regional distribution network, infrastructure that many pediatric oncology centers, particularly in lower-resource settings, do not possess. Conversely, the higher spatial resolution of PET can change management by revealing lesions that SPECT misses, potentially altering surgical planning and response assessment. Whether that incremental diagnostic yield justifies the infrastructure investment is precisely the kind of question that meta-analyses, correspondence, and rebuttals are meant to adjudicate in public, with the reasoning visible to clinicians who must make decisions for individual children.

What the Albano and Treglia reply ultimately illustrates is that the transition from 123I-MIBG to 18F-mFBG in neuroblastoma will be decided not by any single study but by the cumulative weight of carefully scrutinized evidence. The authors of both the original meta-analysis and the critique agree on the fundamentals: mFBG is a promising tracer with genuine physical advantages, and the emerging literature supports its diagnostic potential. Where they differ is in how strongly the current evidence licenses a change in practice. That disagreement, aired transparently in the correspondence columns of Pediatric Radiology, is how the field protects itself against both premature adoption and unwarranted delay. For the children whose scans will guide their treatment in the coming years, the outcome of this technical argument is anything but academic; it will help determine which images their doctors trust, which therapies they become eligible for, and how precisely their disease can be measured from diagnosis through remission.

Subject of Research: Comparison of 18F-metafluorobenzylguanidine PET/CT and 123I-MIBG scintigraphy for neuroblastoma imaging

Article Title: Reply to:18F-Metafluorobenzylguanidine positron emission tomography/computed tomography in neuroblastoma

Article References: Albano, D., & Treglia, G. (2026). Reply to:18F-Metafluorobenzylguanidine positron emission tomography/computed tomography in neuroblastoma. Pediatric Radiology. https://doi.org/10.1007/s00247-026-06769-x

Image Credits: AI Generated

DOI: 10.1007/s00247-026-06769-x

Keywords: neuroblastoma, 18F-mFBG, 123I-MIBG, PET/CT, SPECT, pediatric radiology, nuclear medicine, meta-analysis, norepinephrine transporter, dosimetry, molecular imaging, Reply