Nuclear Medicine’s New Wave: Immune Imaging, Long-Acting Radiopharmaceuticals and Smarter PET Scans

Nuclear medicine is quietly rewriting the rules of how cancer and neurological disease are seen and treated, and a fresh wave of ahead-of-print research from The Journal of Nuclear Medicine offers one of the clearest snapshots yet of where the field is heading. Published by the Society of Nuclear Medicine and Molecular Imaging, the newly released studies span immune-cell imaging in head and neck cancer, long-acting radiopharmaceuticals for neuroendocrine tumors, targeted radiotherapy for CEACAM5-expressing cancers, pediatric neuroblastoma imaging, and a series of rigorous clinical evaluations of PET tracers used in dementia, prostate, breast and kidney cancer. Together, they illustrate a discipline moving decisively beyond anatomy, toward molecular precision, theranostics and truly personalized medicine.

One of the most conceptually striking studies targets the tumor microenvironment itself. Researchers developed and evaluated a PET imaging approach aimed at CD163, a surface marker carried by tumor-associated macrophages, the immune cells that tumors frequently recruit and reprogram to support their own growth. In head and neck squamous cell carcinoma, a malignancy in which the immune landscape often determines how patients respond to therapy, a tracer labeled with copper-64, known as 64Cu-ICT-01, allowed investigators to visualize where these macrophages reside and how their distribution shifts during tumor progression and after treatment. Complementary testing on human tissue confirmed that the tracer binds specifically to CD163, supporting its translational relevance. If validated further, the technique could give oncologists a noninvasive window into immunosuppressive niches within tumors, potentially helping predict which patients will benefit from immunotherapy long before changes in tumor size become apparent.

Theranostics, the pairing of diagnostic imaging with targeted radionuclide therapy, features prominently in the new research. A prospective clinical trial evaluated 177Lu-LNC1010, a long-acting somatostatin analog labeled with lutetium-177, for peptide receptor radionuclide therapy in 22 patients with progressive metastatic neuroendocrine tumors. Long-acting formulations are designed to prolong tumor exposure to the therapeutic radiation while simplifying treatment logistics, and in this trial patients received up to four cycles. The investigators systematically assessed safety, tumor response, absorbed radiation doses delivered to tumors and organs at risk, progression-free survival and overall survival during follow-up. The results add to rapidly growing evidence that radioligand therapy can deliver clinically meaningful disease control in neuroendocrine tumors, a class of cancers that has historically been difficult to treat with conventional chemotherapy.

A second radiopharmaceutical study turned its attention to CEACAM5, a cell-surface protein overexpressed in several cancers, including colorectal cancer, and an established target for both antibody-drug conjugates and radioligand therapy. In laboratory and mouse experiments, a radiolabeled compound designed to bind CEACAM5 selectively attached to CEACAM5-positive cancer cells while demonstrating favorable tumor uptake and reduced accumulation in the kidneys, a critical safety consideration for peptide- and antibody-based radionuclide therapies. Remarkably, a single treatment significantly extended survival in mice bearing CEACAM5-positive tumors, with only mild and temporary toxicity observed. The findings position this agent as a candidate for translation into first-in-human trials and reinforce the broader trend of matching radiopharmaceuticals to molecular signatures rather than tumor locations.

Pediatric oncology also gained a potential new target. Neuroblastoma, an aggressive cancer of the sympathetic nervous system that primarily affects young children, remains one of the most challenging malignancies to image and treat. Researchers examined DLL3, a protein better known from small cell lung cancer, as a candidate target in neuroblastoma. Analysis of human tumor samples and preclinical models revealed that DLL3 is widely expressed and frequently localized on the cell surface, an essential prerequisite for both imaging agents and therapeutic radioligands. DLL3-targeted PET imaging subsequently demonstrated tumor-specific uptake not only in preclinical models but also in four patients with relapsed neuroblastoma, offering early clinical proof of concept. For children with few remaining options, a validated DLL3 pathway could open the door to both molecular imaging and precision radioligand therapy in the future.

Beyond theranostics, several new studies interrogate the reliability of the workhorse technology of molecular imaging itself. Amyloid PET, used to detect the amyloid plaques characteristic of Alzheimer’s disease, has become central to diagnosis and to the growing field of disease-modifying Alzheimer’s therapy. A study of nearly 1,500 amyloid PET scans compared interpretations by local radiologists and nuclear medicine physicians with those of expert readers across three FDA-approved tracers. The good news: agreement was consistently strong, with similar performance for positive and negative scans. Importantly, the study also found that lower reader confidence was associated with reduced agreement, suggesting that confidence ratings could serve as a quality-control signal in routine practice. As amyloid PET demand surges worldwide, the findings provide reassurance that community-based interpretation can keep pace with expert standards.

Prostate cancer, the most active arena in nuclear medicine today, received an unusually detailed quantitative treatment. In a multicenter study, researchers evaluated measurements derived from 18F-piflufolastat PSMA PET/CT, matching PET findings with histopathology from 305 men to determine which imaging metrics best distinguish malignant prostate cancer from benign tissue. Several quantitative measures correlated with malignancy, but the SUVmax-to-blood-pool ratio showed the strongest ability to separate cancerous from benign lesions, both within the prostate and at metastatic sites. Establishing such thresholds is a critical step toward standardizing PSMA PET interpretation, reducing unnecessary biopsies, and enabling radiologists to report results with quantitative, reproducible criteria rather than subjective visual assessment alone.

Combination therapy, meanwhile, may soon be guided by a simple blood test and a PET scan. In an analysis of 37 patients with metastatic castration-resistant prostate cancer receiving 177Lu-PSMA-617 together with pembrolizumab, an immune checkpoint inhibitor, researchers examined whether baseline biomarkers could predict response. Patients with lower levels of circulating tumor DNA at the start of treatment and higher PSMA uptake on PET fared better, while changes in circulating tumor DNA and PSMA PET measurements at 12 weeks reflected both the depth and durability of response. The study points toward a practical biomarker strategy for selecting patients for combined radioligand immunotherapy, one of the most closely watched approaches in advanced prostate cancer.

Breast and kidney cancer imaging rounded out the new research portfolio. In triple-negative breast cancer, the most aggressive breast cancer subtype, a study compared 18F-ATD001, a PARP-targeted PET tracer, with standard 18F-FDG PET/CT in 37 women. The two methods detected similar numbers of lesions, and although the PARP tracer showed lower overall uptake, its signal correlated moderately with FDG in primary tumors, suggesting it may provide complementary biological information about DNA repair enzyme expression that FDG cannot capture. Separately, a prospective study of 68Ga-DPI-4452, a tracer targeting carbonic anhydrase IX, evaluated 30 adults with suspected kidney tumors. The agent identified clear cell renal cell carcinoma with high sensitivity and detected substantially more metastatic lesions than conventional imaging, with tracer uptake strongly correlating with CAIX expression in tumor tissue, a combination of diagnostic accuracy and biological validation that could reshape renal cancer imaging.

Taken together, the ahead-of-print collection paints a picture of a field in confident ascent. Tracers are becoming more biologically specific, imaging metrics are being quantified against gold-standard pathology, and therapy is increasingly delivered by molecules that home in on cancer cells while sparing healthy tissue. From macrophage mapping in head and neck cancer to DLL3 imaging in children with relapsed neuroblastoma, the studies collectively advance the central promise of nuclear medicine and theranostics: diagnosing and treating each patient according to the unique molecular fingerprint of their disease, with the goal of achieving the best possible outcomes.

Subject of Research: Advances in molecular imaging and radiopharmaceutical therapy reported in The Journal of Nuclear Medicine ahead-of-print research

Article Title: The Journal of Nuclear Medicine Ahead-of-Print Tip Sheet: September 11, 2026

Article References: The Journal of Nuclear Medicine Ahead-of-Print Tip Sheet: September 11, 2026. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: nuclear medicine, PET imaging, theranostics, radiopharmaceutical therapy, PSMA PET, neuroendocrine tumors, neuroblastoma, amyloid PET, prostate cancer, triple-negative breast cancer, kidney cancer, tumor-associated macrophages