Advancing and streamlining the development pipeline and translation of theranostic radiopharmaceuticals for application in nuclear medicine necessitates continued cross-sector collaboration among key stakeholders from the Society of Nuclear Medicine and Molecular Imaging (SNMMI), industry partners, and academics to ensure continued growth and innovation and clinical translation. One mechanism the SNMMI has for such dialogue is its biennial Industry Partners Circle (IPC). After the success of prior IPCs, the Center for Molecular Imaging, Innovation, and Translation (CMIIT) hosted the latest IPC in January 2024. The goals of the 2024 CMIIT IPC were to address 4 key priorities that have emerged for the translational community: grow the workforce pipeline, improve academia/industry collaborations to support career development, facilitate radiopharmaceutical clinical trials, and overcome barriers in developing α-therapies. The IPC was attended by SNMMI staff and leadership, members of the CMIIT board of directors, key stakeholders from academia, and industry representatives from a broad range of biopharmaceutical companies and equipment manufacturers. This article summarizes the discussions that were conveyed at the 2024 CMIIT IPC.
Endometriosis is a common gynecologic disorder often associated with chronic pelvic pain, infertility, and reduced quality of life. Conventional imaging modalities, such as transvaginal ultrasound and MRI, may underestimate the extent of disease, particularly in deep infiltrating endometriosis. Fibroblast activation protein (FAP) is highly expressed in remodeling endometrium and has been implicated in endometriotic lesions. This study investigates the feasibility of integrating FAP-targeted PET/MRI to improve endometriosis detection. Methods: This retrospective study included 18 premenopausal women. The test cohort consisted of 9 patients with suspected or confirmed endometriosis who had undergone FAP-targeted PET/MRI or PET/CT with the FAP inhibitor (FAPI) [68Ga]BED003 (previously known as [68Ga]Ga-OncoFAP-DOTAGA). The reference cohort consisted of 9 premenopausal women without known endometriosis who had undergone FAPI PET/MRI or PET/CT with either [68Ga]BED003 or [68Ga]Ga-FAPI-46 for initial staging of breast cancer. Examinations were not scheduled with regard to the patients' menstrual cycles. Lesions were assessed using a segment-based analysis derived from the #Enzian classification. Focal radiopharmaceutical uptake was semiquantitatively assessed using SUVmax and SUVmean Clinical assessments and laparoscopic findings, when available, served as reference standards. Results: In the test cohort with available PET/MRI data (7 patients and 91 segments), MRI alone identified endometriosis-suspicious findings in 19% of segments. In contrast, combined PET/MRI identified findings in 49% of segments. Among all PET datasets (108 segments per cohort), focal extrauterine FAP uptake was observed in 41% of the test cohort's segments compared with 13% of the reference cohort's segments (P < 0.01). The mean number of PET-positive segments per patient was higher in the test cohort than in the reference cohort (4.9 ± 2.4 vs. 1.7 ± 1.3, P = 0.009), with the greatest difference observed in peritoneal, ovarian, and tubal segments. Uterine SUVmax did not differ significantly between the 2 cohorts (P = 0.489). Where available, PET/MRI findings showed substantial concordance with laparoscopic results. Conclusions: FAPI PET/MRI increased the detection of lesions suggestive of endometriosis compared with MRI alone. These findings support further prospective evaluation of FAPI PET/MRI as an adjunct imaging modality for preoperative assessment of endometriosis.
The detection of biochemical recurrence (BCR) of prostate cancer remains challenging, as small-volume disease may fall below the sensitivity of standard imaging. Prostate-specific membrane antigen (PSMA) PET/CT is currently the most sensitive imaging modality for tumor detection at low prostate-specific antigen (PSA) levels, but recurrence continues to be difficult to detect. We evaluated whether routine delayed pelvic imaging at 90 min postinjection improves diagnosis of sites of recurrence in patients referred for BCR. Methods: We retrospectively analyzed 201 patients with prostate cancer undergoing dual-phase 68Ga-PSMA PET/CT for BCR of prostate cancer (median PSA, 0.52 ng/mL). Imaging of vertex to midthighs was acquired at approximately 60 min and delayed pelvic imaging at approximately 90 min postinjection. Two nuclear medicine physicians independently assessed whether delayed imaging improved diagnostic certainty or revealed additional 68Ga-PSMA-avid lesions. Results: Delayed pelvic imaging improved diagnostic certainty for 68 patients (34%) and revealed additional 68Ga-PSMA-avid lesions for 23 patients (11%). Of patients with additional lesions detected on delayed imaging, roughly one third-representing 3% of the total cohort-subsequently received focal radiation dose escalation during treatment planning. Improvements were primarily influenced by increased tracer uptake confirming subtle lesions, reduced bladder or ureteral interference, and differentiation of physiologic from pathologic uptake. All measurable lesions within the field of view of the delayed pelvic image were quantified. The median SUVmax for malignant lesions increased from 4.3 to 5.0, whereas benign lesions remained stable (median SUVmax of 2.7 on normal imaging and 2.6 on delayed imaging). Conclusion: Routine delayed pelvic imaging at 90 min postinjection enhanced lesion detection and diagnostic confidence in BCR of prostate cancer, particularly at low (<1 ng/mL) PSA levels. The addition of this additional acquisition into standard PSMA PET/CT protocols can improve staging accuracy and clinical decision-making.
Accurate estimation of organ and effective doses in CT imaging is essential for risk assessment, protocol optimization, and personalized care in diagnostic radiology and nuclear medicine. We systematically benchmarked MIRDct, a freely available mesh phantom-based CT dose calculation software, against established reference software (National Cancer Institute Dosimetry System for Computed Tomography [NCICT] and VirtualDose [Virtual Phantoms]) by evaluating agreement between organ-absorbed doses and effective doses across representative scanners, phantoms, and protocols. Methods: Organ absorbed and effective doses were calculated for adult and pediatric phantoms for whole-body (WB) and regional (head, chest, abdomen-pelvis [AP]) CT examinations. MIRDct uses mesh-based International Commission on Radiologic Protection (ICRP) reference phantoms with anatomically realistic organ surfaces, whereas NCICT and VirtualDose use voxel-based ICRP 110 and hybrid Rensselaer Polytechnic Institute/University of Florida phantom models, respectively. For each software, volumetric CT dose index (CTDIvol) values were obtained from the software interface using matched acquisition parameters; in MIRDct, these values were derived from scanner console-reported outputs for the corresponding protocol settings. Organ absorbed doses, dose coefficients, and effective doses were computed across 44 matched scanner-phantom-protocol configurations. Inter-software differences were summarized using medians and interquartile ranges. For regional protocols, organ-absorbed doses were stratified by irradiation category (in-field, partial-in-field, out-of-field), to assess field-dependent variability. Results: CTDIvol​ values reported by the 3 software tools showed close agreement across matched protocol configurations, with median inter-software differences not exceeding 7%. For in-field organs, dose coefficients from NCICT and VirtualDose generally agreed with MIRDct values within ±25% across adult and pediatric head, chest, AP, and WB protocols, indicating good agreement in the primary beam region. Larger relative deviations occurred for partial-in-field and out-of-field organs, where doses were scatter-dominated; however, absolute organ doses were less than 2 mGy, limiting clinical relevance. Effective dose estimates showed similar concordance: differences were below 25% for all VirtualDose comparisons except head scans and for WB protocols, whereas adult chest and AP protocols differed by up to 40% relative to NCICT. These differences were associated with variations in phantom anatomy and fixed, pre-tabulated CTDIvol reference values in NCICT and VirtualDose, compared with protocol-specific, console-reported CTDIvol inputs in MIRDct. Conclusion: MIRDct provides organ- and effective-dose estimates that are broadly consistent with established CT dosimetry tools, with agreement typically within ±25% for in-field organs and within a few milligray for absolute doses across adult and pediatric protocols. The use of mesh-based ICRP reference phantoms with anatomically realistic organ surfaces, protocol-specific CTDIvol inputs from the scanner console, and uncertainty propagation supports its application as a research tool for CT dose benchmarking, protocol optimization, and quality assurance in diagnostic CT and nuclear medicine.
The value of [18F]FDG PET/CT imaging in the management of SMARCB1-deficient renal medullary carcinoma (RMC), a rare and aggressive type of kidney cancer, has not been established. We sought to determine the utility of [18F]FDG PET/CT findings for the evaluation of disease burden and treatment planning in patients with RMC. Methods: Using an institutional database, we identified patients with RMC who underwent [18F]FDG PET/CT scans as part of clinical care between 2016 and 2025. When available, baseline [18F]FDG PET/CT images were used; otherwise, the earliest available follow-up scan performed because of concern of recurrence or progression was included. For all scans, sites of abnormal [18F]FDG uptake were assessed, the SUVmax of the most avid site was quantified, and tumor-to-normal tissue ratios (TNRs) were calculated. PET/CT findings were compared with anatomic imaging (CT/MRI-based) performed within 30 d. Instances in which PET/CT findings altered treatment were recorded. Results: On PET, 48 of 49 patients had clearly [18F]FDG-avid disease. The single patient without [18F]FDG-avid lesions also lacked evidence of disease on anatomic imaging. Of the 23 patients who received a baseline PET/CT scan for staging purposes, 15 had intact renal primary tumors, and all tumors were [18F]FDG-avid (median SUVmax, 13.4; range, 9.5-23.5; median TNR blood, 10.7; range, 4.2-16.6). Ten patients were imaged during therapy, and 16 underwent imaging after progression or before the start of a new treatment. Forty-three patients had [18F]FDG-avid nodal metastatic disease (median SUVmax, 8.9; range, 1.8-27.0). Extranodal disease was observed in 36 patients, most commonly in the lungs (n = 24; median SUVmax, 5.8; range, 1.7-17.5) and bones (n = 19; median SUVmax,10.7; range, 3.7-24.8). In 31 patients, [18F]FDG PET/CT identified additional lesions not detected on anatomic imaging, predominantly involving bones (n = 18), lymph nodes (n = 13), and soft tissues (n = 11). These additional findings led to a change in clinical management for 10 (21%) of 48 patients with active disease. In contrast, no lesions were identified on anatomic imaging that were not apparent on PET/CT scans. Conclusion: RMC is a highly [18F]FDG-avid malignancy. [18F]FDG PET frequently detects additional metastatic sites missed by conventional anatomic imaging, facilitating disease extent assessment and optimizing treatment strategy in patients with RMC.
Radiotheranostic therapy (RTT) is an emerging form of personalized cancer care that combines radiopharmaceutical imaging and radiopharmaceutical therapy (RPT). Although promising clinically, the value for money of RTT remains uncertain. The objective of this study is to review the cost-effectiveness evidence of RTT in cancer and critically appraise the methodologies utilized in conducting the included economic evaluations. Methods: A systematic literature review was conducted in accordance with the PRISMA guidelines. A comprehensive search strategy encompassing key search terms related to economic evaluations of RTT in oncology was performed across 7 electronic databases (CINAHL, Econlit, Embase, PubMed, Scopus, Web of Science, and International HTA database), as well as databases of health technology assessment (HTA) agencies (Canada's Drug Agency, Medical Services Advisory Committee, and the National Institute for Health and Care Excellence). The final search was conducted in September 2025 and covered published articles, reports, and HTA appraisals from 2015 to 2025. Methodologic quality was assessed using the CHEQUE framework, whereas reporting quality was evaluated using the CHEERS checklist. Results: Sixteen articles or reports and 9 HTA appraisals were included. Among the radiopharmaceutical imaging studies, 80% evaluated 68Ga whereas all RPT studies assessed 177Lu. Half of the model-based economic evaluations focused on prostate cancer and the rest on neuroendocrine tumors. The modeling approach in the evaluations varied, and the reported incremental cost-effectiveness ratio ranged from $21,350 to $146,526/quality-adjusted life-year for radiopharmaceutical imaging and from $66,761 to $397,342/quality-adjusted life-year for RPTs. HTA agencies identified uncertainties in evidence, comparator choice, and model assumptions and highlighted the absence of real-world considerations such as supply, workforce, and infrastructure constraints. Conclusion: This review identifies substantial heterogeneity and methodologic gaps in the economic evaluation of RTTs, contributing to uncertainty around their value for money. These findings underscore the need for fit-for-purpose HTA frameworks that integrate the full theranostic pathway and address system-level constraints and equity considerations.
We present the design and performance of the newly developed PHAROS-a high-resolution, multifunctional PET system integrating time-of-flight (TOF) and depth-of-interaction (DOI) technologies-and report its first-in-human imaging results for brain and breast applications in multiple patient positions. Methods: The PHAROS system features a movable detector head, transformable patient table, and compact footprint, enabling both seated and supine neuroimaging as well as breast and extremity imaging. The scanner's PET ring comprises 20 detector sectors, each with 3 × 12 block detectors in the evaluated 3-detector-module-ring configuration, providing a 19.6-cm axial field of view. Each block detector consists of 8 × 8 lutetium oxyorthosilicate crystals (1.92 × 1.92 × 15 mm3) coupled to dual 4 × 4 silicon photomultiplier arrays for DOI readout. System performance was assessed using a 3-dimensional Hoffman brain phantom and first-in-human studies, including [18F]FDG brain imaging, [18F]florbetaben amyloid PET, [18F]FP-CIT dopamine transporter PET, and prone-position [18F]FDG breast imaging. All images were reconstructed with 3-dimensional ordered-subset expectation maximization incorporating TOF and DOI information. Results: In the Hoffman phantom, cortical and subcortical structures were sharply visualized without artifacts, and layered activity patterns were clearly resolved in coronal and sagittal planes. In the [18F]FDG brain PET of a healthy volunteer, PHAROS produced high-quality images with well-defined cortical and subcortical uptake patterns and clear gray-white matter contrast. In [18F]florbetaben amyloid PET, the amyloid-negative case showed marked gray-white matter contrast and a characteristic spiculated pattern of white matter tracts, whereas the amyloid-positive case exhibited diffuse cortical binding of radiotracer with the relative sparing of the precentral, postcentral, and occipital cortices. Dopamine transporter PET showed reduced bilateral putaminal binding in a patient with Parkinson disease. In prone breast PET, multiple hypermetabolic masses and skin invasion were clearly delineated with high tumor-to-background contrast, also enabling detailed visualization of tumor heterogeneity. Conclusion: These first-in-human results demonstrate that the PHAROS system achieves remarkable spatial resolution and high image quality across diverse applications. Its versatile design, incorporating DOI and TOF technologies, supports a wide range of clinical and research uses, enabling accurate lesion characterization in both neurologic and oncologic settings.
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are biologically and clinically heterogeneous tumors, most of which overexpress somatostatin receptors (SSTRs). The presence of SSTRs enables staging and allows patient selection for treatment with radiolabeled somatostatin analogs (SSAs), such as DOTATATE. [225Ac]Ac-DOTATATE is an α-emitting radiopharmaceutical in development for the treatment of patients with SSTR2-expressing solid tumors. α particles have a shorter path length and higher linear energy transfer than do β particles, leading to largely irreparable double-strand DNA breaks and cytotoxicity. ACTION-1 (NCT05477576) is a 2-part, randomized, controlled, open-label, phase 1b/3 trial of [225Ac]Ac-DOTATATE in patients with SSTR-expressing GEP-NETs whose disease progressed after 177Lu-labeled SSA therapy. ACTION-1 included a dosimetry substudy to determine the feasibility of obtaining imaging data with 225Ac. The objectives of the substudy were to estimate radiation absorbed doses of [225Ac]Ac-DOTATATE in critical organs and tumors. Methods: [225Ac]Ac-DOTATATE was administered intravenously every 8 wk for 1-4 cycles to adults with grade 1 or 2, well-differentiated, inoperable SSTR2-expressing GEP-NETs that progressed after 2-4 cycles of 177Lu-lableled SSA. Dosimetry was assessed after cycles 1 and 4 of [225Ac]Ac-DOTATATE via SPECT/CT of 221Fr (4.8-min half-life), the first daughter and surrogate for 225Ac and 213Bi (46.6-min half-life, surrogate for later daughters). Absorbed doses and absorbed dose coefficients adjusted for a relative biological effectiveness factor of 5 (ADCRBE=5) to target tissues and tumors were calculated; tumor doses were estimated by MIRD S-value methodology. Results: Dosimetry data were obtained from 9 of 17 patients in phase 1b, each completing 4 cycles. 213Bi mostly remained with DOTATATE in the tumors; a minor fraction went to the kidneys. The estimated absorbed doses to kidneys and red bone marrow were 22.3 and 1.1 Gy, respectively. The ADCRBE=5 to selected tumors ranged from 488 to 8775 mGy/MBq across both treatment cycles. The ADCRBE=5 for most tumors was lower in cycle 4 than in cycle 1; many tumors defined in cycle 1 were unidentifiable in cycle 4. Conclusion: Dosimetry data from ACTION-1 demonstrated the feasibility of image-based dosimetry of 225Ac through SPECT/CT imaging of 221Fr and 213Bi. The 213Bi daughter mostly remained with DOTATATE in tumors, decaying at the same location as 221Fr. The favorable tumor-to-normal tissue absorbed dose ratio of [225Ac]Ac-DOTATATE supports its use in patients with SSTR-expressing GEP-NETs.
First-in-human studies of radiopharmaceuticals include an estimation of human radiation doses often extrapolated from preclinical biodistribution data. We reviewed radiation dose estimates derived from preclinical and clinical studies to determine the utility of preclinical dosimetry studies for estimating the human radiation dose of PET radiopharmaceuticals. Methods: Literature searches were performed for preclinical and clinical studies published between 1990 and 2021 that provided radiation dose estimates for common PET radiopharmaceuticals. Whole-body effective dose and maximum organ absorbed dose coefficients derived from animal and human studies were compared to evaluate their agreement. Ratios of animal-derived to human-derived dose estimates were calculated. Dosimetry data were further stratified by pharmacophore, animal species, and animal-to-human extrapolation method. Results: The SD in radiation dose estimates from clinical studies was generally lower compared with the SD in dose estimates extrapolated from animals. An overlap in the distribution of radiation dose estimates derived from animal and human studies was observed for short-lived radiopharmaceuticals (82Rb-, 15O-, 13N-, 11C-, 68Ga-, 18F-, and 64Cu-labeled, n = 394). The higher dose estimates and larger variability (spread) in preclinical and clinical radiation dose estimates observed for long-lived (89Zr- and 124I-labeled, n = 48) compared with short-lived radiopharmaceuticals highlight important differences in the radiation profile between the 2 groups. Conclusion: Our assessment of the agreement between animal and human radiation dosimetry data for PET drugs indicated a difference between short-and long-lived radiopharmaceuticals in terms of agreement, magnitude, and variability in dose estimates. A closer agreement between animal and human data, relatively lower doses, and lower variability in measured ED values in studies of short-lived PET radiopharmaceuticals suggest that approaches to forego preclinical dosimetry can be developed to facilitate clinical trials of new PET drugs for certain short-lived radionuclides. For first-in-human studies of long-lived PET radiopharmaceuticals or radiopharmaceuticals with long biological turnover, which are associated with higher radiation doses, animal-derived human dose estimates may provide necessary radiation safety information (e.g., identify unexpected high uptake in a particular organ) even though the radiation dose may be underestimated.
Off-line PET imaging after proton therapy is limited by transport delay and by the sensitivity and short axial field of view of conventional scanners, which hinder imaging at ultralow activity and characterization of whole-body biologic washout. We evaluated whether a near-room total-body PET/CT system could enable clinically practical imaging of proton-induced activity after treatment and its whole-body biologic washout. Methods: We conducted a series of phantom studies to evaluate the performance of total-body PET at ultralow activity with Monte Carlo (MC)-simulated activity distributions as references. Nineteen patients with solid tumors underwent off-line total-body dynamic PET/CT imaging shortly after proton therapy. Spatial correlation between PET and MC results was quantified using the Dice similarity coefficient (DSC) and normalized cross-correlation (NCC). Dynamic images were reconstructed, and time-activity curves were extracted from volumes of interest to analyze the dynamic behavior of proton-induced activity. Results: In phantom experiments, PET images showed close spatial correspondence to MC reference distributions under ultralow activity. In patients, the agreement between PET and MC was higher for relatively stationary targets, with a mean DSC/NCC of 0.81 ± 0.09/0.81 ± 0.09 for the brain and 0.81 ± 0.05/0.83 ± 0.08 for the breast. Dynamic total-body PET images revealed biologic washout and whole-body redistribution of isotope activity within and beyond the gross tumor volumes, showing enrichment within the cardiac blood pool, major blood vessels, and blood-rich organs, such as the spleen and liver. Conclusion: Near-room total-body PET/CT enabled interpretable imaging under ultralow activity after treatment. Dynamic total-body imaging additionally captured whole-body biologic washout of proton-induced activity through blood circulation, providing a foundation for future washout modeling and methodologic development for in vivo treatment assessment.
Brain PET is a powerful imaging modality that directly reflects cerebral metabolic activity, making it an essential tool for human brain research. However, conventional brain PET typically requires subjects to remain stationary in a sitting or supine position during scanning. This study evaluated the performance of SmartBrain, a wearable brain PET system for real-time imaging. Methods: SmartBrain uses 192 detectors, with each detector consisting of a 6 × 6 lutetium-yttrium oxyorthosilicate crystal (3 × 3 × 5 mm3) array with a 3 × 3 silicon photomultiplier array. We evaluated the physical performance of SmartBrain in accordance with the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. In addition, we performed 18F-FDG imaging using a custom Hoffman brain phantom and a multilayer Derenzo phantom. Dynamic rat images and the 18F-FDG images from a healthy volunteer are presented. Results: Spatial resolution is 2.29 mm in the center of the field of view. The sensitivity was 720.2 cps/MBq. The peak noise-equivalent count rate was 4.67 kcps at 10.1 kBq/mL, and the scatter fraction was 29.5%. The NEMA image-quality contrast recovery coefficients ranged from 72.9% (10-mm sphere) to 89.4% (37-mm sphere), and background variability was 11.3% at a contrast ratio of 9.4:1. The time-of-flight resolution was 234 ps, and the energy resolution was 10.8%. SmartBrain showed that the main structures of the custom Hoffman brain phantom could be resolved and demonstrated the ability to separate rods as small as 1.7 mm. Conclusion: SmartBrain clearly demonstrated brain structures, confirming its suitability for clinical brain research. Moreover, as a wearable and mobile PET platform, it offers unique opportunities for naturalistic brain imaging and future clinical applications in the diagnosis and management of neurologic disorders.
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Lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 4 or greater on multiparametric MRI (mpMRI) indicate a high likelihood of prostate cancer (PCa), and guidelines recommend a targeted biopsy. We aimed to compare the diagnostic performance of robotic arm-assisted [68Ga]Ga-PSMA-11 PET/CT-guided prostate biopsy (PGPB) with mpMRI-directed cognitive-fusion transrectal ultrasound-guided biopsy (MCFB) in biopsy-naïve men with clinical findings suggestive of PCa. Methods: This prospective, single-center, randomized clinical trial (NCT05137561) enrolled biopsy-naïve men age 50-90 y with elevated levels of prostate-specific antigen (≥4 ng/mL) and abnormal digital rectal examination findings. All participants underwent mpMRI, and those with a PI-RADS score of 4 or greater were randomized into 2 arms. In arm 1, participants underwent PGPB for a [68Ga]Ga-PSMA-avid lesion, and participants in arm 2 underwent MCFB. Participants in arm 1 with PET-negative findings subsequently underwent MCFB, and participants with negative biopsy results underwent PET and PGPB. The primary outcome was the detection of PCa. Secondary outcomes included complication rates and participant-reported pain. Result: Of the 267 participants enrolled, 81.3% (217) had lesions with a PI-RADS score of 4 or greater and were randomized to either PGPB (n = 112) or MCFB (n = 105). PCa was detected in 97.1% of participants (101/104) in arm 1 and 81.0% (85/105) in arm 2 (P < 0.05). PGPB showed higher diagnostic accuracy for PI-RADS 5 lesions (100% vs. 95.1%, P = 0.09). Major complications were observed in arm 2 only (n = 5). Arm 1 had significantly fewer complications (10.8% vs. 51.4%, P < 0.01), a lower median visual analog scale score for pain (3 vs. 5), and shorter procedure times. The core positivity rate was higher in arm 1 (60% ± 20%), despite obtaining fewer cores. Conclusion: [68Ga]Ga-PSMA-11 PCPB demonstrated higher diagnostic performance, fewer complications, and better tolerability compared with MCFB. This approach enables integrated diagnosis and staging, offering a promising alternative for efficient, safe, and accurate evaluation of prostate cancer.
The effectiveness and safety of Auger electron (AE)-emitting epidermal growth factor receptor (EGFR)-targeted panitumumab-197gHg-gold nanoparticles (AuNPs) or nontargeted 197gHg-AuNPs for treating glioblastoma multiforme (GBM) were studied after convection-enhanced delivery (CED) in NOD-Rag1nullIL2rgnull (NRG) mice with orthotopic GBM tumors. We hypothesized that EGFR binding, internalization, and nuclear importation of panitumumab-197gHg-AuNPs would make these radiation nanomedicines more effective than nontargeted 197gHg-AuNPs because of the subcellular range of AEs, but that both would be safe because of their confined localization at the infusion site in the brain after CED. Methods: Localization of 197gHg in NRG mice after CED was assessed by SPECT/CT imaging. Toxicity was evaluated after CED of 1.8 × 1011 to 2.3 × 1011 panitumumab-197gHg-AuNPs (0.9 ± 0.5 MBq) or nontargeted 197gHg-AuNPs (2.6 ± 0.8 MBq) by hematology, blood biochemistry, and body weight monitoring. Mice with U251-Luc tumors were treated with panitumumab-197gHg-AuNPs (1.3 ± 0.3 MBq) or 197gHg-AuNPs (1.1 ± 0.4 MBq), panitumumab-AuNPs or AuNPs, or 0.9% NaCl. Tumor response was assessed by MRI and Kaplan-Meier median survival. Self-absorbed doses in the nucleus of tumor cells from AEs were estimated. Toxicity to the brain was assessed by MRI and ex vivo histologic examination. Results: Both panitumumab-197gHg-AuNPs and 197gHg-AuNPs were confined to the infusion site with no redistribution to healthy brain or other organs. There was no hematologic, liver, or kidney toxicity and no decrease in body weight. MRI at 21 d and 34 d revealed that tumors in mice treated with panitumumab-197gHg-AuNPs or 197gHg-AuNPs were significantly smaller than tumors in mice treated with panitumumab-AuNPs, AuNPs, or 0.9% NaCl. Median survival in mice treated with panitumumab-197gHg-AuNPs (59 d) was significantly longer than that in mice treated with nontargeted 197gHg-AuNPs (43 d) or control treatments (31-33 d). The self-radiation absorbed dose in the nucleus of GBM tumor cells from AEs was 3.2-fold higher for panitumumab-197gHg-AuNPs (40.2 Gy) than for 197gHg-AuNPs (12.2 Gy). Conclusion: EGFR-targeted panitumumab-197gHg-AuNPs were more effective than nontargeted 197gHg-AuNPs for treating U251-Luc human GBM tumors in NRG mice. This approach may offer a safe and effective treatment for GBM that could improve patient survival.
The β--emitter 161Tb is emerging as a promising radionuclide for radiopharmaceutical therapy because of its increased yield of low-energy electrons compared with 177Lu. This results in an increased localized absorbed dose, potentially influencing nephrotoxicity with 161Tb. Because of the excretion and reabsorption in specific kidney tissues of radiopharmaceuticals, substructure-level dosimetry is of interest for improving understanding of radiation-induced kidney damage in radiopharmaceutical therapy. This study investigated the renal dosimetry of [161Tb]Tb-DOTATATE and [177Lu]Lu-DOTATATE in C57BL6/Jjr mice using 2 different dosimetry frameworks. Methods: Detailed biodistribution data were assessed at 5 time points postinjection (15 min, 1 h, 4 or 4.5 h, 24 h, and 72 h). The activity in different nephron substructures was determined by γ-counting of the entire kidney and quantitative digital autoradiography acquisition of kidney sections. Tissue-level activity was distributed between nephron substructures. Simplistic dosimetry assuming uniform absorbed dose distribution was compared with nephron-substructure-level dosimetry based on a multinephron computational model. Results: Both radiopharmaceuticals exhibited similar pharmacokinetics, with rapid renal clearance and peak uptake at 15 min postinjection. 161Tb resulted in a significantly increased absorbed dose heterogeneity across nephron substructures compared with 177Lu. Absorbed doses to proximal tubules were on average 71% higher than to glomeruli for 161Tb and 28% higher for 177Lu. Simplistic whole-kidney dosimetry underestimated proximal tubule absorbed doses by up to 35% for 161Tb and 24% for 177Lu and over- or underestimated glomerular absorbed doses, particularly for 161Tb. The highest absorbed doses were observed in the juxtamedullary nephrons for both radionuclides, reflecting their distinct morphology. Conclusion: Nephron-substructure-level dosimetry revealed substantial absorbed dose heterogeneity for both radiopharmaceuticals, which is not considered with simplistic whole-organ dosimetry. Small-scale dosimetry enables identification of possible dose-limiting nephron substructures, informing future nephroprotective strategies and improving the translational evaluation of novel radioligands.
We evaluated the diagnostic performance of fibroblast activation protein inhibitor (FAPI) PET for lesion detection at breast cancer diagnosis and response assessment after neoadjuvant chemoimmunotherapy (NAC) and compared these findings with those from [18F]FDG PET or histopathology after the completion of NAC. Methods: A systematic search across PubMed, EMBASE, Web of Science, and Cochrane Trial databases up to January 12, 2026, was conducted. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Extracted data included SUVmax, tumor-to-background ratio, and lesion detection in studies comparing FAPI PET with [18F]FDG PET. For studies comparing FAPI PET with histopathology, diagnostic performance parameters were obtained. Data on FAPI uptake, stratified by histology type, molecular subtype, and tumor grade, were extracted. Results: The literature search yielded 3662 studies, 13 of which were included in this review. Of these, 10 compared FAPI PET with [18F]FDG PET and 3 compared FAPI PET findings with those of histopathology after the completion of NAC. The reported mean SUVmax range was 6.5-17.1 versus 3.9-8.3 for primary tumors, 5.1-17.1 versus 1.2-10.3 for axillary lymph node metastases, and 4.9-21.7 versus 1.7-8.1 for distant metastases on FAPI PET versus [18F]FDG PET, respectively. FAPI PET detected more lesions compared with [18F]FDG PET in all evaluated anatomic sites. In post-NAC response assessment of the breast tumor, FAPI PET reported a sensitivity and specificity of 73%-100% and 71%-100%, respectively. Lower FAPI uptake was observed in low-grade, luminal A tumors and in those with lobular histology. Conclusion: FAPI PET demonstrated increased lesion detection compared with [18F]FDG PET at the time of breast cancer diagnosis and demonstrated considerable diagnostic performance for assessing response evaluation after NAC.
For mouse brain PET imaging with high quantification accuracy, ultrahigh resolution is essential. Metabotropic glutamate receptors are important molecular targets, linked to various neurologic diseases. Here, we report the comparison of in vivo mouse brain images obtained with sub-0.5-mm resolution PET and those obtained with autoradiography using 4-18F-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide (18F-FITM) that binds to metabotropic glutamate receptor subtype 1. Methods: We recently developed a sub-0.5-mm resolution PET scanner having an axial coverage of 23.4 mm and an inner diameter of 48 mm. The PET scanner comprises 32 depth-of-interaction detectors, each of which has staggered 3-layer lutetium-yttrium-orthosilicate crystal arrays with a pitch of 0.8 mm. A resolution phantom was used to evaluate the imaging performance of the PET scanner. Dynamic PET imaging was performed to evaluate the concentration changes of 18F-FITM at various mouse brain regions. In vivo metabotropic glutamate receptor imaging of a mouse brain was performed using 18F-FITM and the PET scanner. Subsequently, autoradiography images of the same mouse brain were obtained using 18F-FITM. Results: The 0.45-mm rod structure was resolved with the PET scanner. Time-activity curves of various mouse brain regions were obtained. The sub-0.5-mm resolution PET visualized 18F-FITM uptake in the mouse brain with high correlation to the autoradiography images. Conclusion: The sub-0.5-mm resolution PET opens up new opportunities for translational neuroscience research using mice models.
The use of radioactive iodine (RAI) for patients with thyroid cancer (TC) who are also treated with hemodialysis for end-stage renal disease (HD-ESRD) remains challenging, with several issues still unresolved. We report our tertiary referral center experience and provide suggestions for management improvement. Methods: We included all HD-ESRD patients that required RAI for TC in our institution. Oncologic results and toxicity risk were evaluated. Blood marrow (BM) absorbed dose was estimated on the basis of current guidelines and compared with 2 alternative models that adapt to the inability of using biexponential models for hemodialyzed patients. We emulated the impact of high RAI activity on the BM absorbed dose. Dialysis parameters were reviewed to correlate with kinetics of RAI activity. The impact of 2 different schema of recombinant human thyrotropin stimulating hormone was also studied. Results: In total, 16 patients were included. Fifteen patients were prepared with recombinant human thyrotropin stimulating hormone (5 with 1 injection on day 2, 10 with 2 injections on days 10 and 2). Median RAI activity was 2913 MBq, and immediate and late tolerance was good. The median BM absorbed dose was 0.72, 0.81, and 0.67 Gy with models 1, 2, and 3, respectively, statistically different among all calculation methods. There was no significant correlation between total blood activity decrease and total purified blood volume. No patient crossed the 2-Gy threshold with a delivered activity of 3700 MBq. Conclusion: On the basis of the largest series of HD-ESRD patients treated with RAI for TC, we present findings that could enhance their management. With our hemodialysis protocol, we suggest that routine reductions in RAI activity may be overly cautious and unnecessary. Oncologic outcomes were favorable, without significant hematologic toxicity. A 65-70 L of purified blood volume per session target results in over 90% reduction in radioactivity after 2 dialysis sessions.
The impact of salvage radiotherapy (SRT) on overall survival (OS) in patients experiencing biochemical recurrence (BCR) of prostate cancer remains an area of active investigation. The international multicenter PROMISE registry provides a valuable dataset to explore the association between SRT and long-term clinical outcomes in this patient population (NCT06320223). Methods: Comprehensive restaging at the time of BCR was performed by integrating both serologic markers and advanced molecular imaging (PET/CT or PET/MRI), offering an accurate assessment of molecular imaging (mi) TNM stage. Results: In total, 1410 patients experiencing BCR with prior prostatectomy were included. The median follow-up was 5.2 y (interquartile range, 3.8-6.9 y). SRT was administered after PET to 381 of 680 patients (56.0%) with PET-negative disease (miT0N0M0) and to 478 of 730 patients (65.0%) with PET-locoregional disease (miT/N+ M0). SRT was associated with longer OS in the entire cohort (hazard ratio, 0.66; 95% CI, 0.47-0.93; P = 0.019) with 5- and 7-y survival rates of 95.2% (95% CI, 93.6%-96.8%) and 90.8% (95% CI, 88.1%-93.6%), respectively. Without SRT, 5- and 7-y survival rates were 92.1% (95% CI, 89.6%-94.7%) and 83.8% (95% CI, 79.8%-88.1%), respectively. Subgroup analysis found significant benefit for patients with miT0N0M0 disease (hazard ratio, 0.42; 95% CI, 0.22-0.78; P = 0.0061), particularly those with a prostate-specific antigen level of 0.5 ng/mL or lower (P = 0.03, log-rank test). Conclusion: SRT improves OS for patients with BCR, especially those with a negative prostate-specific membrane antigen-targeted PET.