The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

To develop and validate deep learning (DL) segmentation models for accurate, MRI-less amyloid PET quantification through the Centiloid scale. In this retrospective study, two DL models (PET/CT and PET-only) were trained using 2774 18F-FBP PET/MRI scan pairs from the ADNI dataset, where synthetic CT were generated from T1w MRI and used as training data. External validation was performed on 424 PET/CT scans from the OASIS-3 dataset. The performance of the DL models was compared to the MRI-based FreeSurfer reference method and the template-based rPOP method. Statistical analyses included the calculation of mean absolute error (MAE), R-squared (R²), equivalence testing, and diagnostic accuracy for amyloid positivity (Centiloid > 20), with a focus on the 0–40 Centiloid ‘gray zone’. The PET/CT model demonstrated the highest accuracy, with a MAE of 5.79 Centiloid and a strong correlation (R² = 0.96). The PET-only and rPOP methods showed higher errors with MAEs of 10.8 and 14.45 Centiloid, respectively. The PET/CT model’s Centiloid values were shown to be equivalent to the MRI-derived values within a ± 5 margin, while the PET-only and rPOP methods were not. In the Centiloid gray zone subgroup (n = 93), the PET/CT model yielded the highest diagnostic accuracy of 90.3

BACKGROUND:CD8 T cells mediate the effects of cancer immunotherapies. CD8 positron emission tomography (PET) imaging with [89Zr]Zr-berdoxam-crefmirlimab enables whole body CD8 cell assessment and has been shown to be safe in Phase I evaluation. The correlation between CD8 PET imaging parameters and the quantity of CD8 cells assessed by the gold standard of immunohistochemistry (IHC) is unknown. METHODS:The Phase II, prospective multicenter study (iCorrelate) tested the correlation between CD8 PET and CD8 cells by IHC of core needle biopsies from patients with solid tumors receiving immune checkpoint blockade. The safety of repeat CD8 PET was additionally analyzed. RESULTS:49 patients had 70 biopsies (37 baseline and 33 on-treatment) for correlating CD8 PET with IHC. Standard uptake value mean of the biopsied tumor normalized to aorta showed a correlation with IHC of 0.49 (95% CI 0.26 to 0.59). The correlation was 0.71 (95% CI 0.48 to 0.85) in patients with renal cell carcinoma. Repeat CD8 PET imaging on-treatment was safe. CONCLUSIONS:We found a modest correlation between CD8 PET with [89Zr]Zr-berdoxam-crefmirlimab and intratumoral CD8 cell counts, likely because core needle biopsies do not fully represent the intratumoral heterogeneity of the CD8 cell distribution. Continued research is essential to evaluate in vivo CD8 PET signals, autoradiography, and CD8 T-cell presence by IHC in fully resected tumors. Further studies investigating the correlation between CD8 PET and immunotherapy outcomes are necessary to determine whether CD8 PET imaging could become a valuable tool for guiding immunotherapy development and informing clinical decision-making.

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors and low expression of the human epidermal growth factor receptor 2 gene. Radiolabeled amino acids (AAs) have the ability to specifically target the enhanced AA transport and modified metabolic pathways present in breast cancer cells. The primary objective of this study was to compare the uptake of AA PET tracers targeting different AA transporter systems in 2 mouse models to assess their potential for imaging TNBC. Methods: The AA PET tracers (R)-3-[18F]fluoro-2-methyl-2-(N-methylamino)propanoic acid (18F-MeFAMP, system A transport), (S)-2-amino-3-[1-(2-[18F]fluoroethyl)- 1H-[1,2,3]triazol-4-yl]propanoic acid (18F-AFETP, cationic and neutral transport), and 18F-fluciclovine (system ASC transport) were compared with 18F-FDG in primary tumor orthotopic syngeneic (4T1, n = 10) and patient-derived xenograft (BCM3936, n = 8) models of TNBC. SUV, tumor-to-brain ratios, and tumor-to-muscle ratios were quantified. Quantitative analysis of AA transporter immunohistochemistry was conducted and compared with the imaging results. Results: AA PET tracers demonstrated uptake levels in primary TNBC tumors comparable to those with 18F-FDG, with varying uptake across tracers. All AA tracers demonstrated higher tumor-to-normal tissue ratios than did 18F-FDG across multiple organs. The highest tumor-to-brain ratios were observed for 18F-MeFAMP (4T1 model) and 18F-AFETP (PDX BCM3936 model). 18F-MeFAMP showed the highest tumor-to-muscle ratios in both models, followed by 18F-AFETP and 18F-fluciclovine. Tumor-to-bone and tumor-to-liver ratios consistently favored AA tracers, with 18F-AFETP demonstrating superior tumor-to-liver contrast because of low hepatic uptake. 18F-MeFAMP, 18F-AFETP, and 18F-fluciclovine showed positive but complex correlations between SUV and corresponding AA transporters in immunohistochemical analysis. Conclusion: The AA PET tracers evaluated in this study demonstrated promising imaging properties in TNBC models compared with 18F-FDG, with higher tumor-to-brain ratios and tumor-to-muscle ratios observed across both models. Although these findings highlight the potential of AA tracers for imaging primary tumors and metastases, they also support the continued investigation of AA PET tracers as complementary tools to 18F-FDG to characterize TNBC biology as well as other aggressive cancers.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

Background: Targeted molecular imaging utilizing positron emission tomography (PET) technology may provide a non-invasive biomarker in idiopathic pulmonary fibrosis (IPF). Translocator protein (TSPO, 18kDa), a mitochondrial outer membrane protein, is upregulated in persistent injury and inflammation. Hence, we evaluated the TSPO-targeting PET tracer [ 18 F]DPA-714, to detect disease activity in IPF. Methods: In this prospective study, 7 participants with IPF and 3 healthy controls (HCs) were enrolled, all confirmed as either mixed- (MAB) or high-affinity binders (HAB) based on genotyping for SNP rs6971 polymorphism in the TSPO gene. Imaging was performed on a GE 710 PET/CT scanner with respiratory gating 30–60 minutes after IV administration of [ 18 F]DPA-714. Regions of interest were defined using non-contrast CT. Mean and maximum standardized uptake values (SUVmean, SUVmax) were measured in whole lung, mediastinal, and axillary lymph nodes (all participants), and fibrotic lesions (IPF only). Results: Participants with IPF had a median age of 74 years; 71% were male. HCs had a median age of 47 years. Five participants were HABs(3 IPF,2 HCs) and five were MABs(4 IPF,1 HC). In IPF, mediastinal lymph node SUVmax was significantly higher than axillary lymph nodes [median 5.3,(4.5,6.8) vs 2.1,(1.8,2.4),p = 0.02], and fibrotic lesions demonstrated 2.5-fold higher SUVmean than normal lung [median 4.1(3.9,5.1) vs 1.6(1.2,2.2),p = 0.02]. Mediastinal lymph node uptake was numerically higher in IPF than HCs within affinity groups, while total lung SUVmean varied. Conclusion: TSPO imaging with [ 18 F]DPA-714 PET is safe and feasible in IPF and this study supports further prospective evaluation as a potential predictive biomarker. Trial Registration Clinicaltrials.gov (NCT04362644), Date of registration 4/23/2020

PURPOSE:Fibroblast activation protein (FAP) is an attractive target for radiopharmaceutical therapy. Phase I of the LuMIERE study (ClinicalTrials.gov, NCT04939610) investigated the safety of [177Lu]Lu-FAP-2286 (177Lu-FAP-2286) in heavily pretreated patients with advanced solid tumors and identified the recommended phase II dosage (RP2D). PATIENTS AND METHODS:LuMIERE is a prospective, open-label, nonrandomized, phase I/II, multicenter study. Phase I followed a Bayesian optimal interval design evaluating four escalating activity levels of 177Lu-FAP-2286 (3.70, 5.55, 7.40, and 9.25 GBq). Patients were selected by positive [68Ga]Ga-FAP-2286 (68Ga-FAP-2286, also known as [68Ga]Ga-HKG301) PET/CT imaging on all target lesions [maximum standardized uptake value (SUVmax) ≥1.5× SUVmean of mediastinal blood pool]. 177Lu-FAP-2286 was administered intravenously every 6 weeks for ≤6 cycles. The primary endpoint was dosage-limiting toxicities (DLT) and treatment-emergent adverse events (TEAE). RESULTS:Of 35 patients imaged with 68Ga-FAP-2286, 27 received 177Lu-FAP-2286 (3.70 GBq, n = 3; 5.55 GBq, n = 6; 7.40 GBq, n = 7; 9.25 GBq, n = 11). Two DLTs were observed: one patient who received 5.55 GBq of 177Lu-FAP-2286 experienced grade 4 lymphopenia, and one patient who received 9.25 GBq experienced grade 3 hemoptysis; these were the only treatment-related grade ≥3 TEAEs. All-cause grade ≥3 TEAEs were reported for 11 patients (40.7%). The RP2D for 177Lu-FAP-2286 monotherapy was determined to be 9.25 GBq. Preliminary Response Evaluation Criteria in Solid Tumors efficacy findings demonstrated a partial response in 1 patient and stable disease in 10 patients (maintained for at least two assessments in 6 patients). CONCLUSIONS:177Lu-FAP-2286 was well tolerated in patients with advanced solid tumors. The safety and preliminary efficacy findings support its continued development in phase II.

TPS611 Background: GPC3 is an oncofetal protein expressed in up to 75% of hepatocellular carcinomas (HCCs) and associated with poor prognosis. Its selective expression in tumor and not in normal tissue makes it a promising target for radiopharmaceutical imaging and therapy (theranostics). The GPC3-selective diagnostic RYZ811 ([ 68 Ga]Ga-RAYZ-8009) and therapeutic α particle-emitting RYZ801 ([ 225 Ac]Ac-RAYZ-8009) are a theranostic pair. Previous studies show high uptake of RYZ811 in intrahepatic and extrahepatic HCCs, with low normal liver background uptake. In GPC3+ HCC mouse models, single administrations of RYZ801 significantly inhibited tumor growth. Methods: RYZ801-101 is a single-arm, open-label, phase 1/1b study of RYZ811 and RYZ801 in previously treated patients with GPC3+ unresectable HCC. The study has two parts: dose escalation (part 1) and dose expansion (part 2). Each part consists of two stages: RYZ811 imaging and RYZ801 treatment. The aim of imaging is to determine if RYZ811 safely and adequately identifies patients with GPC3+ tumors. The aim of treatment is to determine the safety, pharmacokinetics (PK), recommended phase 2 dose (RP2D; part 1), and preliminary antitumor activity (part 2) of RYZ801. Key eligibility criteria are: confirmed HCC; Barcelona Clinic Liver Cancer stage B or C; Child-Pugh A; ≥1 RECIST v1.1-measurable lesion (treatment stage); and disease progression after ≥1 systemic therapy in part 1 and 1 prior line in part 2. In part 1, approximately 60 patients will receive RYZ811 (185 MBq) in the imaging stage; up to 30 of these will receive escalating doses of RYZ801 (2.6–5.5 MBq × 4 doses) in the treatment stage. In part 2, approximately 80 patients will receive RYZ811 (185 MBq) in the imaging stage; up to 40 of these will receive RYZ801 at the RP2D in the treatment stage. Primary RYZ811 objectives are to assess the safety/tolerability and biodistribution of RYZ811. Secondary objectives are to determine absorbed doses (ADs) to organs and tissues and any association between RYZ811 uptake and RYZ801 efficacy. Primary RYZ801 objectives are to identify the RP2D and safety/tolerability of RYZ801. Secondary objectives are to assess PK, ADs to critical organs and tumors, and preliminary antitumor activity. Enrollment for Part 1 is ongoing in the USA. Clinical trial information: NCT06726161 .

PET/MRI has been established as a clinical imaging modality with a wide range of applications. In pediatric imaging, it has been shown to provide valuable diagnostic information for a variety of indications and clinical questions. Despite the increasing availability of clinical PET/MRI, its routine use for pediatric patients is still primarily limited to large clinical and academic centers. One reason is the high complexity of pediatric PET/MRI, which requires thorough patient preparation and examination planning, skilled image acquisition, and careful image interpretation. The authors provide practical guidance to support the clinical implementation of pediatric PET/MRI and thus increase its availability to pediatric patients. To this end, the authors provide an overview of technical prerequisites, imaging protocols, clinical indications, and image analysis strategies. These aspects are illustrated with clinical examples provided by established clinical pediatric PET/MRI programs worldwide. ©RSNA, 2025 Supplemental material is available for this article.

Background/Objectives: Medical research institutions are increasingly leveraging artificial intelligence (AI) to enhance the processing and analysis of medical imaging data. However, scaling AI-driven medical image analysis often requires specialized expertise and infrastructure that individual labs may lack. A centralized solution is to establish a core facility—a shared institutional resource—dedicated to Automated Medical Image Processing and Analysis (AMIPA). Methods: This technical note offers a practical roadmap for institutions to create an AI-based core facility for AMIPA, drawing on our experience in building such a resource. Results: We outline the key components for replicating a successful AMIPA core facility, including high-performance computing resources, robust AI software pipelines, data management strategies, and dedicated support personnel. Emphasis is placed on workflow automation and reproducibility, ensuring researchers can efficiently and consistently process large imaging datasets. Conclusions: By following this roadmap, institutions can accelerate AI adoption in imaging workflows and foster a shared resource that enhances the quality and productivity of medical imaging research.

Objectives: Annexin-A1 is a 37 kDa phospholipid-binding protein which is concentrated in a truncated 34 kDa form (AnnA1) in caveolae on the tumor vascular endothelial cell surface with expression in many tumor types. PRISM developed the monoclonal mouse antibody mAnnA1 against AnnA1 for evaluation of AnnA1 as a potential target for imaging and therapy in oncology. mAnnA1 was humanized to make hAnnA1 for translation to clinical studies. Both PRISM-produced mAnnA1 and cGMP contractor-produced hAnnA1 were investigated using noninvasive PET/CT imaging, and dosimetry was evaluated to enable clinical translation of this strategy and to investigate in vivo behavior of hAnnA1. Methods: Antibodies mAnnA1 and hAnnA1 (PRISM “hAnnA1-P” or contractor generated “hAnnA1-C”) were conjugated with the chelator deferoxamine and evaluated for immunoreactivity with ELISA. Conjugated antibodies were radiolabeled with zirconium-89. Naïve mice, rats, and non-human primates (NHP) were injected with [89Zr]mAnnA1 or [89Zr]hAnnA1 and imaged with PET/CT up to 10 days post injection. After imaging, mice and rats were euthanized and organs were collected, weighed, and radioactivity was quantified using a gamma counter. Dosimetry in mice and NHPs were calculated using OLINDA. Results: [89Zr]mAnnA1 showed similar biodistribution to other antibodies with slow clearance through the liver. Transition to [89Zr]hAnnA1-C during the dosimetry studies revealed substantial uptake in the spleen (130 ± 48% ID/g at day 5 post injection in female BALB/c), which was not observed with [89Zr]mAnnA1 (5.6 ± 1.7% ID/g at day 7 PI). Further studies in multiple strains of mice showed variable elevated splenic uptake of [89Zr]hAnnA1-C across mouse strains, with the highest uptake observed in female BALB/c mice (118.4 ± 23.1% ID/g) and the lowest uptake observed in male CD1 mice (34.7 ± 10.2% ID/g). Additionally, splenic uptake of hAnnA1-C was observed in Fischer rats (2.8 ± 0.6% ID/organ) and NHPs (1.6 ± 0.6% ID/organ), although at lower levels than what was observed in BALB/c mice (8.8 ± 1.8% ID/organ). Dosimetry results showed similar values between estimates based on mouse and NHP data, with the largest difference seen in the spleen (5.2 vs. 2.6 mSv/MBq in females respectively). Sequencing of hAnnA1-C revealed a frameshift mutation in the antibody sequence introduced during cGMP manufacture. Restoration of the antibody sequence by PRISM returned the antibody distribution into alignment with mAnnA1. Conclusions: An aberration introduced during cGMP production of hAnnA1-C resulted in increased splenic uptake and alteration of the biodistribution in mice. PET imaging enabled quantitative detection of the immunogenic behavior of hAnnA1, which led to detection of the sequence error. Restoration of the sequence resulted in an antibody which was non-immunogenic to mice.

Fibroblast activation protein (FAP) is a type II integral membrane glycoprotein, highly expressed on the cell surface of cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers and showing limited expression in normal tissues. Given this expression profile, FAP appears to be a promising target for radioligand therapy that has pan-cancer potential. [177Lu]Lu-NNS309 is a FAP-targeted radiopharmaceutical that shows improved tumor retention and demonstrates promising anti-tumor activity in translationally relevant preclinical models (e.g., PDAC, NSCLC) where FAP is expressed on CAFs. CFXX489A12101 (NCT06562192) is a first-in-human phase I, open-label, multi-center study of [177Lu]Lu-NNS309 in patients with pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), breast cancer (BC), and colorectal cancer (CRC). The study includes a dose escalation part followed by a dose expansion part. Key eligibility criteria include prior treatment for locally advanced unresectable or metastatic disease and having all measurable lesions (per RECIST 1.1) showing [68Ga]Ga-NNS309 uptake on positron emission tomography/computed tomography (PET/CT). Patients who are eligible for treatment receive one dose of [177Lu]Lu-NNS309 on day 1 of each cycle. A 6-week and a 4-week dosing schedule will be explored. Dosimetry data will be obtained from patients in the dose escalation part after the first dose and will be used to calculate the cumulative radiation exposure. Dose escalation will be guided by a Bayesian hierarchical logistic regression model with overdose control (EWOC) principle, and assessment of all relevant data available from all dose levels including safety, tolerability, clinical dosimetry, pharmacodynamics, and preliminary efficacy. Once the recommended dose(s) (RD) and schedule(s) of [177Lu]Lu-NNS309 are determined, the expansion part may open and will include patients with locally advanced or metastatic PDAC (n∼20), locally advanced or metastatic NSCLC (n∼20), HR+/HER2- ductal BC (n∼15), HR+/HER2- lobular BC (n∼15), and triple negative BC (; n∼24).The primary objectives of the study are to evaluate the safety and tolerability of [177Lu]Lu-NNS309 and to identify the RD(s) and regimen(s) of [177Lu]Lu-NNS309 for further clinical evaluation. Secondary objectives of the study are to evaluate the preliminary anti-tumor activity of [177Lu]Lu-NNS309, characterize the pharmacokinetics of [177Lu]Lu-NNS309 in blood and urine, the radiation dosimetry for organs and tumor lesions, and to evaluate the safety and imaging properties of [68Ga]Ga-NNS309. The study is currently enrolling in the dose escalation part. Ravit Geva, Daniel Juneau, Shadi Abdar Esfahani, Cristiano Ferrario, Farshad Moradi, Amir Iravani, Jordi Ahnert, Ivan Manuel Victoria Ruiz, Thibaud Koessler, Aitana Calvo Ferrandiz, Bernard Doger de Speville, Patrick Flamen, Albiruni Razak, Desiree Deandreis, Laure Al-Mansour, Niklaus Schaefer, James Nagarajah, Hilde Nienhuis, Marco Maccauro, Angelina Filice, Jonathan Goldman, Ken Herrmann, Matthias Eiber, Alexander Drzezga, Martin Heuschkel, Jonathan McConathy, Johnson Geoffrey, Ephraim Parent, Yasutoshi Kuboki, Shizuka Origuchi, Xuan Mai Couillebault, Elisa Garcia Garayoa, Jayarama Naidu Roopa, Christopher Straub, Dominik Hainzl, Xinyu Chen, Fang Yang, Eirini Pectasides, Brandon Mancini. Phase I open-label, multi-center study to evaluate the safety, tolerability, dosimetry, and preliminary activity of FXX489 ([177Lu]Lu-NNS309) in patients with pancreatic, lung, breast and colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT112.