Polyarteritis nodosa (PAN) is a rare systemic necrotizing vasculitis. It affects the medium-sized arteries. It attacks many parts of the body in very different ways. Therefore, it is difficult to diagnose and stage. 18F-fluorodeoxyglucose (18F-FDG) PET/CT combines anatomic and metabolic activity. This can show the complete extent of the disease in PAN very well. We report a 35-year-old man with fever, generalized myalgia, black stools and dry gangrene at the tip of his fingers. Laboratory tests revealed high C-reactive protein and high erythrocyte sedimentation rate. However, the anti-neutrophil cytoplasmic antibodies (ANCA) were negative. 18F-FDG PET/CT identifies multisystem lesions. The doctor thought that these lesions were there, but they could not be found by regular scanning. These lesions include high activity of many muscles, more absorption of the middle artery of the calf, local absorption of the skin between the toes, and absorption of the stomach wall. Tissue samples from many places confirmed necrotizing arteritis. After treatment with corticosteroids and targeted antibiotics, the patient's condition improved.
BACKGROUND:Recurrent hypopharyngeal carcinoma is associated with poor prognosis, yet the prognostic utility of maximum standardized uptake value (SUVmax) from 18F-FDG PET/CT and its relation to recurrence site remain insufficiently characterized. OBJECTIVE:This study aimed to evaluate the association of SUVmax and recurrence site with overall survival (OS) in patients with recurrent hypopharyngeal carcinoma. METHODS:We retrospectively analyzed 69 patients with biopsy-confirmed recurrent hypopharyngeal carcinoma without distant metastasis treated at Viet Nam National Cancer Hospital between 2019 and 2024. PET/CT scans performed at recurrence diagnosis were used to measure SUVmax at the primary tumor and/or metastatic lymph nodes. Patients were classified by recurrence site: primary tumor only (Tumor-only), lymph nodes only (Node-only), or both (Tumor + Node). OS was assessed using Kaplan-Meier estimates and Cox proportional hazards regression, adjusted for age, ECOG, time to recurrence and type of treatment. RESULTS:Mean SUVmax was 12.3 ± 6.3. Patients with SUVmax > 12 had a median OS of 11.45 months (95% CI: 7.1-37.1) vs. 13.06 months (95% CI: 6.7-37.4) for SUVmax ≤ 12 (P < 0.01). Tumor + Node recurrence had a median OS of 11.2 months (95% CI: 6.8-37.4) vs. 13.6 months (95% CI: 6.7-34.5) for Tumor-only/Node-only (P = 0.009). In multivariate Cox regression, SUVmax > 12 (HR = 2.69, 95% CI: 1.37-5.30, P = 0.004), Tumor + Node recurrence (HR = 2.96, 95% CI: 1.45-6.06, P = 0.003), Non-surgery treatment (HR = 2.98, 95% CI: 1.23-7.23, P = 0.016) and ECOG PS ≥ 2 (HR = 2.22, 95% CI: 1.12-4.41, P = 0.023) independently predicted reduced OS. CONCLUSION:Elevated SUVmax and combined tumor-nodal recurrence on PET/CT are significant predictors of reduced OS, supporting their role in prognostic stratification for recurrent hypopharyngeal carcinoma.
Fibroblast activation protein (FAP) is highly expressed in various sarcomas, including solitary fibrous tumors (SFTs). In recent years, radiolabeled FAPI tracers have emerged as potential therapeutic targets. In SFTs with high FAP expression, 90Y-FAPI-46 demonstrated promising therapeutic efficacy. These findings highlight the potential of FAPα expression as a clinically relevant biomarker for patient selection and establish 90Y-FAPI-46-based radiopharmaceutical therapy as a promising and meaningful therapeutic option for patients with malignant SFT.
OBJECTIVE:Immunotherapy plays a pivotal role in the treatment of colorectal cancer (CRC). PD-L1 has been identified to be a significant biomarker of response to treatment. The assessment of PD-L1 presently depends on biopsy samples - a problem that may be resolved with the help of a molecular imaging approach. This study devised and evaluated an 18F-and 89Zr-labelled albumin-binding PD-L1-targeted VHH for potential diagnostic imaging in CRC models. METHODS:PD-L1 expression was initially validated in HCT-116 cell-derived xenografts and CRC20-PDX tumors. An albumin-binding moiety was conjugated to a PD-L1-targeted VHH to construct SN-2D01. The 18F-labeled SN-2D01 was prepared using the AlF-RESCA chelation strategy and the probe was modified with DFO for a 89Zr radiolabeling process. The evaluation of [18F]F-SN-2D01 and [89Zr]Zr-SN-2D01 through PET imaging was performed on the two tumor models and a quantitative analysis of tumor uptake for each tracer. Ultimately, a biodistribution study of [89Zr]Zr-SN-2D01 at 120 h post-injection (p.i.) was performed in both tumor models. RESULTS:The HCT-116 cell-derived xenografts and CRC20-PDX tumors were both PD-L1-positive, with a higher expression observed in lesions from CRC20-PDX versus HCT-116 tumors. The 2 h p.i. of [18F]F-SN-2D01 PET showed clear visualization of HCT-116 and CRC20-PDX tumors, with tracer mostly cleared via hepatic and renal excretion. In PET imaging with [89Zr]Zr-SN-2D01, the tumor uptake in both HCT-116 and CRC20-PDX slowly increased from 24 h to 120 h p.i, which peaked at 120 h. Biodistribution at 120 h showed tumor uptake of 11.49 ± 1.32 %ID/g for the CRC20-PDX model and 8.12 ± 1.54 %ID/g for the HCT-116 model. CONCLUSION:In summary, we presented two PET probes to visualize PD-L1. Of these, [89Zr]Zr-SN-2D01 was found to have significant capability to evaluate PD-L1 expression in CRC. The PD-L1-targeted SN-2D01 may provide a new approach in radionuclide therapy targeting PD-L1 in CRC.
Prostate cancer (PCa) remains a leading cause of cancer-related morbidity and mortality worldwide, underscoring the need for improved molecular imaging strategies. Although prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has changed prostate cancer imaging and treatment, its clinical utility is limited in some settings by heterogeneous tumor expression and substantial off-target uptake in organs such as the kidneys and salivary glands. Acid phosphatase 3 (ACP3), also known as prostatic acid phosphatase, has regained attention as an alternative prostate-associated target because of its abundant expression in prostate cancer and comparatively low expression in several normal tissues. Recent advances in high-affinity small-molecule ligands, including radiolabeled OncoACP3 derivatives, have enabled the development of ACP3-targeted PET radiopharmaceuticals. Preclinical studies and early clinical investigations demonstrate favorable biodistribution, high tumor-to-background contrast, and the capacity to detect lesions in PSMA-low or PSMA-negative disease. Moreover, ACP3-directed radioligand strategies highlight its potential in theranostic applications. Overall, ACP3 radiopharmaceuticals may provide a complementary approach for precision prostate cancer imaging and therapy.
To predict bilateral renal curves and glomerular filtration rate (GFR) following unsuccessful tracer injection in SPECT renal dynamic imaging using a Transformer model, thereby obviating the need for repeat examinations. We retrospectively studied patients who underwent repeat imaging post-extravasation (2015-2025). Patient height, weight, serum creatinine, urea, uric acid, and renal dynamic curves were used as inputs to develop a Transformer deep learning model for calibrating curves and predicting GFR. Following injection extravasation during SPECT renal dynamic imaging, the proposed model achieved a high overall alignment with the ground truth curves (Median R2>0.93). However, performance variability was observed, with a small subset of outliers showing poor fit (minimum R2<0) due to complex noise artifacts. For the left kidney, the model achieved an R2 of 0.9288, with 91.78% of predictions falling within a clinically acceptable tolerance of ±5 ml/min of the ground truth. Similarly, for the right kidney, the R2 reached 0.9216, with an accuracy rate of 93.15% based on the same tolerance threshold. It is important to note that the ±5 ml/min criterion was used strictly as a statistical threshold to define 'clinical accuracy' and did not involve any modification of the predicted values. In conclusion, a Transformer model can accurately calibrate and predict bilateral renal curves and GFR values after injection extravasation in SPECT renal dynamic imaging, potentially enhancing clinical workflow efficiency and diagnostic accuracy.
This report describes the 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging of spinal instrumentation incidentally found in a 71-year-old male with extensive degenerative spinal disease. Hardware was noted at L5-S1, a common site of lumbar degeneration and cause of radiculopathy. 18F-NaF showed intense focal uptake at the instrumentation site, while 18F-FDG demonstrated minimal uptake. These findings suggest remodeling of bone (18F-NaF) at the site of instrumentation in the setting of benign physiological metabolic activity (18F-FDG). Other signs of structural deterioration were observed in the cervical and thoracic regions, such as osteophytes and ossification of the posterior longitudinal ligament. We present these findings in the context of a literature review of published studies that utilized 18F-NaF or 18F-FDG PET imaging for the assessment and monitoring of patients with spinal instrumentation.
T lymphocytes are central mediators of cardiovascular disease, driving myocardial injury in myocarditis, transplant rejection, post-infarct remodeling, atherosclerosis, and post-viral syndromes. Yet current imaging tools ([18F]FDG PET, somatostatin receptor tracers, CXCR4 PET, and cardiac MRI) offer only indirect or nonspecific measures of immune activity. The ability to noninvasively visualize and quantify T-cell infiltration and activation could transform diagnosis and management in cardio-immunology. Advances in immuno-PET have produced a growing arsenal of T-cell specific tracers. CD8-targeted agents (89Zr-Df-IAB22M2C) and small-molecule probes such as [18F]F-AraG have entered early clinical trials, demonstrating feasibility and safety in humans. Other tracers, including CD4- and CD3-directed antibodies, IL-2R and OX40 probes, checkpoint tracers (PD-1, CTLA-4), and granzyme B ligands, remain largely preclinical but show strong potential for cardiovascular translation. Applications span acute myocarditis, noninvasive transplant rejection surveillance, assessment of post-MI immune remodeling, plaque vulnerability in atherosclerosis, and systemic immune activation in long COVID. Compared with existing imaging modalities, T-cell PET offers cell-type specificity, quantitative longitudinal monitoring, and the capacity for whole-body immune mapping, particularly when integrated with total-body PET or hybrid PET/MR. Challenges include low T-cell density in the myocardium, tracer specificity, radiation burden, and the need for histopathologic validation. Future directions involve repurposing oncology tracers for cardiology, engineering antibody fragments with improved kinetics, and establishing T-cell PET as a mechanistic biomarker in cardiovascular clinical trials. With further innovation and validation, T-cell PET has the potential to evolve from an experimental tool into a clinically actionable modality, reshaping the management of immune-mediated heart disease.
Myocardial perfusion imaging (MPI) has served as a cornerstone of coronary artery disease (CAD) evaluation for over four decades, including many other cardiac diseases. MPI is extremely valuable for both diagnostic and prognostic purposes in clinical environments, enabling clinicians to evaluate a patient's coronary health. Perfusion scanning utilizes two primary imaging techniques: single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Each relies on radioactive tracers, which are radioactive substances injected into a patient that spread across myocardial tissue and emit photons or positrons detectable by cameras. Traditional radiotracers include 15O-water, 13N-ammonia, and 82Rb-chloride for PET and 99mTc-sestamibi for SPECT, which vary in physical and biological properties, including half-life and extraction fraction, influencing image quality, workflow, and clinical utility. Recently, a new PET radiotracer called 18F-Flurpiridaz has shown promise for increased efficiency among traditional radiotracers, such as a substantially longer half-life. Additional advantages of this radiotracer include, but are not limited to, improved cost-effectiveness due to the use of a pre-existing delivery system, superior image quality, mid-exercise testing, and solving "imaging deserts", which are regions with a lack of medical imaging services that rural areas face. We aim to review the advantages and disadvantages of 18F-Flurpiridaz PET and compare its effectiveness against traditional PET and SPECT tracers in this article.
Monoamine oxidase B (MAO-B) is a key astrocytic biomarker implicated in neuro-inflammation and neurodegenerative diseases. This study reports the development and evaluation of novel fluorine-18 (18F) PET radiotracers for selective MAO-B imaging by exploiting deuteration strategies to address metabolic instability of existing probes. A literature compound [18F]GEH200449 ([18F]4) was synthesized through redesigned labeling precursor, and its deuterated analogue, [18F]4-D2, was prepared to improve metabolic stability. Systematic evaluation using PET imaging, radiometabolite analysis, and autoradiography was performed. While both tracers demonstrated favorable blood-brain barrier penetration, they didn't exhibit region-specific binding consistent with MAO-B distribution in vivo. Furthermore, [18F]4 underwent substantial metabolic degradation in both central and peripheral compartments, and deuteration failed to provide significant stabilization in [18F]4-D2. Autoradiographyfurther revealed non-selective binding of [18F]4-D2to both MAO isoforms. Overall, the translational potential of [18F]4 and [18F]4-D2 remains limited by poor metabolic stability and insufficient target selectivity. Future tracer design should focus on pharmacophore optimization to achieve reliable and selective MAO-B PET imaging.
Xerostomia is a disabling side-effect of head and neck cancer (HNC) radiation therapy (RT) that significantly impacts quality of life. While proton therapy offers dosimetric advantages over photon therapy, metabolic evidence of tissue-sparing effects remains limited. This retrospective study assessed 18F-FDG PET/CT for evaluating radiation-induced metabolic changes in parotid glands following proton versus photon RT in 50 HNC patients with base-of-tongue tumors treated with photon (n=14, intensity-modulated radiation therapy (IMRT)) or proton (n=36, pencil-beam scanning intensity-modulated proton therapy (IMPT)) with concurrent chemotherapy. All patients received 18F-FDG PET/CT before and approximately 3 months post-treatment. Bilateral parotid glands were manually delineated and averaged per patient. Both groups demonstrated significant total mean standardized uptake value (SUVmean) increases (photon: 1.13±0.23 to 1.45±0.38, P<0.001; proton: 1.30±0.27 to 1.41±0.21, P=0.017), with significantly greater increases in the photon group for both ΔSUVmean (0.32 vs. 0.11, P=0.017) and ΔSUVmax (0.44 vs. 0.07, P=0.011; Mann-Whitney U tests). Between-group effect sizes were large (Cohen's d=0.86 and 0.95, respectively), and multivariable regression confirmed the treatment group effect (ΔSUVmean β=-0.25, P=0.017, adjusting for baseline SUV and disease stage; ΔSUVmax β=-0.30, P=0.015, adjusting for baseline SUV). These findings suggest that proton therapy produces significantly lower increases in parotid gland 18F-FDG uptake compared to photon therapy, supporting 18F-FDG PET/CT as a quantitative biomarker for radiation-induced parotid gland injury. Future prospective studies correlating metabolic changes with functional outcomes are warranted.
A growing number of advanced neuroimaging studies have been used to evaluate the nature of consciousness. Such studies have focused on various states of consciousness as well as ways of inducing altered states of consciousness. Various states of consciousness include the normal waking state, sleep states, the brain under anesthesia, and the impact of disorders such as seizures or schizophrenia. The induction of altered states of consciousness includes practices such as meditation or the use of psychoactive substances leading to psychedelic effects. This paper reviews some of the relevant research and then considers some of limitations and challenges for studying consciousness with neuroimaging, particularly via positron emission tomography (PET), single photon emission computed tomography (SPECT), and advanced magnetic resonance imaging (MRI) modalities.
We assessed the performance of a deep convolutional neural network (CNN) in detecting pediatric lymphoma lesions on [18F]FDG-PET/MRI. We evaluated CNN's sensitivity, specificity, percentage agreement, and processing time compared to the interpretations of a pediatric radiologist and a second-year radiology resident. In this retrospective study, a CNN was trained on annotated [18F]FDG-PET/MRI scans from 53 pediatric lymphoma patients and tested on 30 additional scans. The CNN and two human readers recorded the presence of lesions in five anatomical regions. An additional pediatric radiologist and a nuclear medicine physician determined the reference standard. The sensitivity and specificity of the CNN were compared with those of human readers using the McNemar test, and the detection time of the CNN and human readers was compared using the Wilcoxon signed-rank test. The CNN demonstrated higher sensitivity (84.6%) and specificity (93.7%) than the radiology resident (69.2%, P=0.023; 81.5%, P<0.001), but lower than the pediatric radiologist (98.7%, P<0.001; 99.5%, P<0.001). The CNN achieved 83% agreement with the reference standard (95% CI: 79%-87%), higher than the resident's 63% (95% CI: 59%-69%) but lower than the pediatric radiologist's 94% (95% CI: 92%-97%). The median values and interquartile ranges for the time taken (in minutes) were 4 (3, 5) for the CNN, 8 (7, 10) for the pediatric radiologist, and 15 (9, 20) for the radiology resident. The sensitivity, specificity, and percentage agreement of the CNN were higher than those of a radiology resident but lower than those of a pediatric radiologist. The CNN readout was significantly faster compared to both human readers.
Ovarian cancer (OC) was most often diagnosed at an advanced stage due to poor symptoms, the lack of an effective screening method and the limitations of examinations for the early detection of the disease. Sadly, the surgical approach is not possible for all patients, therefore the neoadjuvant chemotherapy (NACT) was a good standard approach before the complete cytoreduction. Currently we don't have indisputable and definitive directives about tools to predict the anatomopathological response. This study investigates the potential of 18FDG-PET in predicting the histological response in high grade epithelial OC before NACT treatment. Ten advanced primarily inoperable OC patients treated with NACT were recruited into this prospective study, then 4 patients could be eligible to analyze, with 12 target lesions eligible to comparative analyses with 18FDG-PET against histological analyses. All patients after NACT presented clinical and biological responses, with normalization of CA 125. Four patients, with 12 resections specimens identified to corresponding 18F-FDG-PET/CT imagery, had showed concordant aspects of response. This preliminary study has demonstrated the role in predictive response of 18FDG-PET, but the complexity in comparative analyses of morpho-functional imagery and histological study includes many difficulties. Thus, to obtain statistically robust results, a large-scale study must be conducted, based on these very encouraging results.
Estrogen receptor (ER) is highly expressed in approximately 95% of invasive lobular breast cancer (ILC) and represents a key target for endocrine therapy. 18F-fluoroestradiol (18F-FES), a radiolabeled estrogen analog, specifically binds to ER and enables real-time, non-invasive, and whole-body evaluation of ER functional status, providing intuitive visualization of the spatial and temporal heterogeneity of ER expression. 18F-FES PET/CT sensitively detect primary tumor and distant metastases and accurately identifies axillary lymph node involvement in ILC. Therefore, 18F-FES PET/CT can serve as a valuable diagnostic tool that can guide the selection of appropriate therapeutic strategies for patients with ILC.
C-X-C chemokine receptor 4 (CXCR4) is a G protein-coupled receptor implicated in immune regulation, tumor progression, and therapy resistance. In lymphoma, CXCR4 overexpression promotes malignant cell survival via microenvironmental retention and activation of pro-survival pathways, correlating with poor prognosis. Its extracellular localization makes it a strong candidate for selective molecular imaging and targeted therapy. This review summarizes recent advances in CXCR4-targeted agents for lymphoma. Peptide-based radiotracers (68Ga-Pentixafor, [18F]AlF-NOTA-QHY-04, [68Ga]Ga-BL02) and small molecules ([64Cu]AMD3100, [18F]MCFB) offer high specificity and favorable pharmacokinetics for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging. Therapeutic strategies include peptide antagonists (BL-8040, Balixafortide), radioligand therapies ([177Lu]Pentixather, [177Lu]Lu-BL02), small-molecule inhibitors (Plerixafor, WK1), and monoclonal antibodies (PF-06747143, Ulocuplomab, LY2624587). These approaches have demonstrated efficacy in reducing tumor burden and enhancing chemosensitivity. Key challenges include off-target uptake due to physiological CXCR4 expression and compensatory signaling via CXCR7. Future directions involve dual-receptor targeting, nanoparticle-based delivery, and integration into precision oncology for both hematologic and solid tumors.
To obtain qualitatively and quantitatively accurate positron emission tomography (PET) images, the recorded PET emission data must be corrected for photon attenuation. Attenuation correction (AC) factors are typically estimated from X-ray computed tomography (CT) data acquired during an integrated PET/CT study. Estimating these factors from magnetic resonance (MR) data in an integrated PET/MR scanner is challenging, as MR images don't provide direct information about annihilation photon attenuation. Conditional generative adversarial networks (cGANs) have shown promising results for both emission-based and MR-based AC. This study explored whether combining these approaches could further improve brain PET AC accuracy. Thirty-five patients who received same-day whole-body PET/MR and PET/CT scans participated in this study. The non-attenuation-corrected and non-scatter-corrected (NASC) PET, MR, and CT reconstructed head regions were cropped and automatically co-registered. Four networks were trained to translate NASC PET and MR images into pseudo-CTs. Three used single-modality input, and the fourth used multi-modality. The multi-modality cGAN produced significantly better pseudo-CTs vs. the single-modality cGANs, with an average structural similarity index (SSIM) and dice similarity coefficients for bone, soft-tissue, and air of 0.865±0.001, 0.715±0.002, 0.915±0.001, and 0.567±0.004, respectively, vs. 0.841±0.001, 0.660±0.003, 0.894±0.001, and 0.524±0.005, for the single-modality cGANs with the best results. When comparing the AC PET reconstructed images, all cGANs outperformed the clinical atlas-based method used in commercially available PET/MR systems, and, as expected, the multi-modal cGAN achieved the highest quality results with average SSIM, and peak signal-to-noise ratio of 0.9987±0.0001, and 50.0±0.4, respectively, vs. 0.9913±0.0024, and 44.3±0.3 for the atlas method.
Conventional single-photon emission computed tomography (SPECT) relies on mechanical collimators, which impose an inherent trade-off between spatial resolution and sensitivity. A novel cardiac SPECT system that employs a self-collimating design with interleaved mosaic scintillators has been proposed, which markedly enhances sensitivity without compromising resolution. However, the unique self-collimating and closely arranged detector geometry also introduces more complex scatter distribution and increased scatter fractions, making accurate scatter correction essential yet technically challenging. We employed a 3D U-Net framework to directly predict scatter-corrected images from uncorrected images. The network was trained using 36 distinct XCAT phantoms based on GATE simulations, with the true scatter-corrected images (true-SC) precisely obtained from the simulations serving as labels. Quantitative evaluation was performed using another two XCAT phantoms with different contrast levels: a high-contrast phantom (H-Phantom, 10 realizations) and a low-contrast phantom (L-Phantom, 5 realizations). The proposed U-Net approach were compared with two triple energy window (TEW) methods (trapezoidal and triangular). For both contrast levels, the U-Net-based approach achieved higher contrast recovery coefficients, myocardium-to-blood-pool ratios closer to the true-SC, higher contrast-to-noise ratios, and lower relative noise compared to the TEW methods. In addition, the U-Net-based method produced images with higher structural similarity and lower normalized mean square error relative to the true-SC reference, compared with the TEW-corrected images. In conclusion, the proposed 3D U-Net-based scatter correction method provides more accurate scatter estimation and superior quantitative performance for self-collimating SPECT systems than conventional TEW approaches.
Prostate-specific membrane antigen (PSMA) radioligands used for PET imaging of prostate cancer (PCa) have variable urinary excretion. The prostate bed region is an important site of disease localization where intense bladder activity may obscure lesion detection. We performed a comparative analysis of bladder activity across different PSMA radioligands and investigated the impact of furosemide administration on reducing bladder activity. We analyzed the PSMA PET/CT images of patients with PCa who were imaged with 68Ga-PSMA-11 with/without 20 mg furosemide, 18F-PSMA-1007, 18F-DCFPyL, 18F-rhPSMA-7.3 with/without 20 mg furosemide. We determined and compared bladder volume and bladder activity level using mean and maximum standardized uptake values (SUVmean and SUVmax) between PET scans obtained with the different PSMA radioligands using an ANOVA or Kruskal-Wallis test, as appropriate. We also determined the association between the bladder activity level versus bladder volume using Spearman correlation. 210 PSMA PET/CT studies were reviewed, including 50, 20, 20, 28, 42, and 50 completed with 18F-PSMA-1007 without furosemide, 18F-rhPSMA-7.3 without furosemide, 18F-rhPSMA-7.3 with furosemide, 68Ga-PSMA-11 without furosemide, 68Ga-PSMA-11 with furosemide, and 18F-DCFPyL without furosemide, respectively. The median bladder SUVmean (range) without furosemide were: 1.75 (0.4-6.4) [18F-PSMA-1007], 10.00 (1.9-140.0) [18F-rhPSMA-7.3], 15.92 (2.0-106.0) [68Ga-PSMA-11], and 25.7 (7.9-87.6) [18F-DCFPyL], (P<0.001). With 20 mg furosemide co-administered with the radiotracer, there was a significant decline in bladder activity level (median SUVmean of 10.00 (1.9-140.0) to 2.95 (0.8-17.6) for 18F-rhPSMA-7.3 and 15.92 (2.0-106.0) to 10.21 (2.6-281.3) for 68Ga-PSMA-11 and a significant increase in bladder volume, P<0.05. There was a significant negative correlation between bladder SUVmax and bladder volume for the entire cohort, P=0.008, r=-0.181. There is variation in the bladder radioactivity between the different PSMA radioligands for PCa PET imaging, with 18F-PSMA-1007 demonstrating the lowest, 68Ga-PSMA-11 and 18F-DCFPyL the highest, and 18F-rhPSMA-7.3 intermediate bladder activity level. Administration of 20 mg furosemide produces a significant reduction in bladder activity and an increase in bladder volume. With 20 mg furosemide, bladder activity of 18F-rhPSMA-7.3 approaches that of 18F-PSMA-1007.
Theranostics is an interesting area of cancer research that describes the use of radiotracers to first diagnose and then treat cancer. By coupling a radioisotope to an agent that selectively targets malignant cells, one can distribute focused radiation to disease sites. There are a variety of different radiopharmaceutical vectors that have been utilized in this way, such as peptides, small molecules and antibodies. Because antibodies bind to highly specific antigens, radioimmunotherapy (RIT) offers a promising route to precisely targeted treatments with reduced systemic toxicity compared to conventional radiotherapy. Beta (β)-emitting isotopes (e.g., 131I, 90Y) have been more commonly coupled in RIT, but the use of alpha (α)-emitters (e.g., 225Ac, 212Pb), for RIT (α-RIT) has rising popularity due to their shorter tissue range and higher linear energy transfer. These characteristics decrease off-target effects in neighboring tissues and increase tumor cell destruction, respectively. However, there are several challenges to RIT. The production of daughter isotopes from α decay makes dosimetric assessments difficult and could potentially cause off target toxicities. Additionally, whole antibodies tend to accumulate in liver tissue and have long biological clearance times, which may cause excess radiation to the blood, marrow and liver. Yet, there are a variety of α-RIT agents currently in development to treat prostate cancer, hematologic malignancies, and other solid tumors. Many agents show promise, like 227Th-epratuzumab, a CD22-targeting antibody used in the treatment of relapsed or refractory acute myeloid leukemia (R/R AML). While notoriously deadly and difficult to treat, the disease control rate in patients with R/R AML taking 227Th-epratuzumab was 38%. Like many α-RIT therapies, follow-up studies are needed to continue to improve efficacy. Strategies to widen the therapeutic indices of these agents have been investigated such as pretargeting, use of antibody fragments, chelator optimization and combination therapies. This review describes the current landscape and clinical progress of targeted α radioimmunotherapy.
