
Muscle-invasive bladder cancer (miBC) is an aggressive malignancy that can be visualised with [64Cu]Copper-dichloride ([64Cu]CuCl2) PET/CT, due to the increased copper avidity of this cancer. Moreover, [64Cu]CuCl2 could also show a predictive role in patients undergoing platinum-based chemotherapy, since both metals enter the cell via the same transporter, CTR-1. In this study, we tested the prognostic and predictive power of [64Cu]CuCl2 PET/CT in miBC. Patients with available [64Cu]CuCl2 PET/CT images and follow-up data were included in the study. Volumes-of-interest (VOIs) were drawn on the primary tumour, nodal metastases, and distant metastases; their sum was defined as the whole-body tumour volume. From these VOIs, SUVmax, SUVmean, SUVmin, Volume, and total lesion copper uptake (TLC) were extracted. These parameters were compared with progression-free survival (PFS), disease-specific survival (DSS) and chemotherapy response. Thirty patients (six women) were included. SUVmean of the primary (p < 0.05), as well as its SUVmax, volume, and TLC (p < 0.01), were higher in patients with disease progression and in those who died of disease. Whole-body tumour volume (p = 0.001) and the presence of metastases (p = 0.024) were independent predictors of PFS; whole-body tumour volume was the only parameter with borderline significance in the DSS model (p = 0.067). Patients progressing under chemotherapy had a higher whole-body tumour volume and TLC (p < 0.05) than those who didn’t. [64Cu]CuCl2 can assess the presence of miBC within the bladder and at remote localisations, providing an accurate estimate of the disease burden at the time of examination, which, in turn, enables prognostic assessment in these patients. Moreover, rather than being a predictor of platinum-based chemotherapy effectiveness, copper uptake signals tumour aggressiveness and resistance to this systemic treatment.
Adipose tissue may contribute to systemic inflammation in breast cancer. This study evaluated whether visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) [18F]fluorodeoxyglucose ([18F]FDG) uptakes on positron emission tomography/computed tomography (PET/CT) are associated with inflammatory indices after adjustment for PET-derived tumor metabolic burden and whether metastatic status modifies these associations. In this retrospective single-center cohort (n = 358) undergoing baseline [18F]FDG PET/CT, metastatic status was defined using an internal three-level clinical stage grouping: early-stage or locally advanced disease was classified as M0 and metastatic disease was classified as MET. VAT and SAT FDG uptakes were quantified as z-scored mean standardized uptake values normalized to lean body mass (SULmean) using the James lean body mass equation. Inflammatory indices from complete blood counts were log-transformed. Prespecified linear regression models with heteroskedasticity-consistent type 3 (HC3) robust standard errors were adjusted for age, body mass index (BMI), fasting glucose, stage, molecular subtype, and PET-derived primary-tumor metabolic burden metrics. Effect modification was tested via exposure × MET interaction. Sensitivity analyses used total-body tumor burden metrics in MET and recalculated SUL using the Janmahasatian lean body mass equation; overall survival (OS) was explored with Cox models. Of 358 patients, 284 (79.3
This study compared the diagnostic performance of [18F]FDG and [68Ga]Ga-Pentixafor PET/CT in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and assessed clinicopathological characteristics and uptake parameters. Participants with RAIR-DTC were prospectively enrolled and underwent both [18F]FDG PET/CT and [68Ga]Ga-Pentixafor PET/CT within two weeks. Images were visually and semi-quantitatively analyzed, with lesion number, location, and uptake parameters recorded. The diagnostic performance of the two tracers was compared, and correlations of uptake parameters with clinicopathological characteristics were further evaluated. Nineteen patients with RAIR-DTC (median age, 60 years) were analyzed. A total of 125 lesions were identified, with 92.8
To evaluate hyperpolarized (HP) γ-glutamyl-[1-13C]glycine ([13C]GG) MRI as a non-invasive method for assessing liver injury through imaging of hepatic enzymatic activity. In this prospective preclinical imaging study, five mice underwent HP 13C MRI at baseline and 48 h after induction of acute liver injury with carbon tetrachloride (CCl4). Dynamic slice-selective HP 13C spectra through the liver were acquired at 3 T. Signals from [13C]GG and its cleavage product [1-13C]glycine (catalyzed by γ-glutamyl-transferase or GGT) were quantified. Glycine-to-GG area-under-the-curve (AUC) ratios were calculated. Paired comparisons were analyzed using a two-tailed t-test. Liver histopathology was analyzed after imaging. At baseline, HP [13C]GG demonstrated detectable in vivo hepatic conversion to [1-13C]glycine. Following CCl4-induced injury, glycine production decreased in all animals despite similar substrate delivery. On average, the glycine-to-GG ratio declined by 25
Immunotherapies are transformative strategies in modern oncology, utilizing the body's own immune system to stimulate and enhance the antitumor immune response. Successful immunotherapies require precise delivery, real-time monitoring of immune reactions, and flexible treatment strategies that can adapt to patient-specific complexities. These conditions underscore the need for noninvasive, longitudinal imaging approaches to understand therapy progress and maximize response towards precision immunotherapies. Photoacoustic (PA) imaging, especially when integrated with ultrasound (US), is a powerful modality that is gaining momentum in the immunoimaging space. PA imaging enables label-free assessment of functional biological parameters using endogenous chromophores, while engineered exogenous contrast agents extend its capabilities for molecular and cellular imaging towards theranostic applications. These advances allow visualization of immune activity, therapeutic distribution, and treatment-induced microenvironmental changes in real-time. In this review, we focus on the integral role of US/PA imaging in guiding, optimizing, and advancing cancer immunotherapy. This review begins by outlining label-free imaging techniques and the use of exogenous contrast agents as theranostic nanoplatforms in cancer immunotherapies. Following this foundation, we explore US/PA imaging in immunotherapies, emphasizing photoimmunotherapy, adoptive cell immunotherapy, immune checkpoint blockade, and focused ultrasound mediated immunomodulation. Additionally, we highlight complementary multimodal imaging approaches that expand the scope of US/PA guided immunotherapy. Finally, we address key translational challenges, emerging innovations, and future directions for translating US/PA into routine clinical practice.
Overexpression of FcRn in multiple hematologic and solid cancers makes it a promising target for monoclonal antibodies, though its presence in healthy tissue calls for proper assessment of toxicity. Here, we report the preclinical development and evaluation of [225Ac]Ac-Macropa-rozanolixizumab, a proof-of-concept FcRn-targeted α-radioimmunotherapeutic. Using a site-specific approach based on interchain disulfide re-bridging, rozanolixizumab was conjugated with Macropa by a PEG4 linker and radiolabeled with actinium-225 in mild aqueous conditions. FcRn binding, immunoreactivity and cytotoxicity were assessed in vitro. Following a single dose administration, biodistribution, dosimetry, and antitumor activity were studied in CHO-FcRn xenograft-bearing mice. Conjugation produced a homogeneous product (chelator-to-antibody ratio 3.3 ± 0.2; > 96
To evaluate the feasibility of collagen-binding ⁶⁸Ga-CBP8 PET/MR for the noninvasive detection of deep infiltrating endometriosis. A single-case exploratory application of ⁶⁸Ga-CBP8 PET/MR was conducted in a patient with endometriosis as a preliminary step toward a larger IRB-approved prospective study. Imaging was performed 60 min after intravenous administration of ⁶⁸Ga-CBP8. Fused PET/MR images were qualitatively assessed for focal tracer uptake exceeding background. Surgical pathology, assessed in a blinded fashion, served as the reference standard. A 32-year-old woman with history of endometriosis completed the examination without adverse events. PET/MR demonstrated focal ⁶⁸Ga-CBP8 uptake corresponding on MR to a T2-hypointense plaque located between the left adnexa and the sigmoid colon, suspicious for deep pelvic endometriosis with bowel involvement. Surgical pathology confirmed endometriosis infiltrating the colonic muscularis mucosae and pericolonic tissue with dense fibrosis. ⁶⁸Ga-CBP8 PET/MR is a feasible and promising technique to noninvasively detect deep infiltrating endometriosis, warranting validation in larger prospective studies. ClinicalTrials.gov, NCT06377553. Date of first enrollment: February 5, 2025. Registered April 22, 2024.
Prostate-specific membrane antigen (PSMA) is a central target for prostate cancer theranostics. Androgen receptor (AR) signaling has been implicated in regulating PSMA expression; however, whether different modes of AR pathway inhibition uniformly translate into enhanced functional radioligand uptake, particularly for therapeutic applications, remains incompletely defined. AR-positive (LNCaP, C4-2) and AR-negative (PC3 PSMA +) prostate cancer models were investigated; parental PC3 cells served as PSMA-negative controls. Cells were treated with the direct AR antagonists enzalutamide and apalutamide or with the androgen biosynthesis inhibitor abiraterone. PSMA surface expression was quantified by flow cytometry. Functional uptake of [18F]PSMA-1007 and [177Lu]Lu-PSMA I T was assessed by gamma counting. Glucose metabolism was evaluated using [18F]FDG uptake, and PSA secretion was measured as a pharmacodynamic readout of AR pathway inhibition. Direct AR antagonism significantly increased PSMA surface expression in AR-positive models and translated into enhanced uptake of the therapeutic radioligand [177Lu]Lu-PSMA I T, with particularly pronounced effects in the castration-resistant C4-2 model. Diagnostic tracer uptake was also increased, though less consistently across models. In contrast, abiraterone did not induce consistent functional enhancement of radioligand accumulation despite PSMA upregulation in selected settings. AR-negative PC3 PSMA + cells exhibited stable baseline PSMA expression but showed no significant changes in PSMA levels or radioligand uptake following AR antagonist treatment. [18F]FDG uptake was reduced under AR inhibition in AR-positive models, indicating that enhanced PSMA-targeted uptake was not driven by global metabolic activation. Direct AR antagonism enhances functional PSMA availability and increases short-term uptake of PSMA-targeted radioligands in AR-positive prostate cancer models. These findings provide mechanistic support for AR-mediated modulation of PSMA-targeted radioligand delivery and warrant further translational investigation.
Programmed death-ligand 1 (PD-L1) is highly expressed in tumour cells and the tumour microenvironment, mediates tumour immune evasion, and is a key target for cancer immunotherapy. Immunohistochemistry (IHC), as a conventional method for PD-L1 detection, has limitations such as invasiveness, temporal and spatial heterogeneity, and an inability to provide dynamic monitoring. In contrast, PD-L1-targeted molecular imaging enables non-invasive, quantitative, and whole-body visual assessment of PD-L1 expression, offering a precise tool for patient selection, treatment response prediction and dynamic monitoring in immunotherapy, and has thus become a focal point in precision oncology research. This paper systematically reviews the development trajectory of PD-L1-targeting radiotracers, including monoclonal antibodies, peptides, nanobodies, aptamers and small molecules. It summarises the targeting performance, pharmacokinetics, imaging efficacy and safety in preclinical and clinical studies; compares the advantages and suitable applications of different types of tracers; analyses the challenges currently facing the field, such as the lack of evaluation standards, tumour heterogeneity, insufficient clinical translation and a scarcity of multicentre data; and offers a prospect on the standardisation of PD-L1-targeted molecular imaging, the integration of diagnosis and treatment, multimodal imaging and its promotion and application in primary care settings. To date, more than 40 PD-L1-targeting tracers have undergone preclinical or clinical validation, with non-invasive imaging demonstrated to be feasible in over 100 cancer patients; early data support further in-depth research and clinical translation in this field.
The AMPA receptor (AMPARs) mediates fast excitatory neurotransmission and is the central to synaptic plasticity, learning and memory dysregulation of this system has been implicated in epilepsy, neurodegeneration, and neuropsychiatric disorders. The transmembrane AMPA receptor regulatory protein γ8 (TARP γ8) plays a crucial role in the expression and localization of AMPARs within the brain, particularly in the hippocampus and cortex. A selective positron emission tomography (PET) ligand to image this target is of significant interest for investigating potential clinical AMPAR/TARP γ8 antagonists. This study describes the development and preclinical evaluation of a potent and selective tracer targeting TARP γ8, [18F]JNJ-1. The binding potency of JNJ-1 was evaluated using a calcium flux assay in HEK-293 cells. The radiotracer was synthesized on an automated synthesizer via a one-step substitution. TARP γ8 target expression in brains was confirmed through immunohistochemistry (IHC), and adjacent brain sections were used for autoradiography (ARG). In vivo assays were conducted in rats, knockout mice, and non-human primates by [18F]JNJ-1 PET imaging and JNJ-1 microdosing studies. JNJ-1 exhibited very high binding potency to TARP γ8, IC50 = 50 pM. Immunoreactivity of TARP γ8 showed high intensity in the hippocampus and moderate levels in the cortex across mouse, rat, and monkey brains. A microdosing with JNJ-1 study revealed high, moderate, and low levels of JNJ-1 uptake in the hippocampus, cortex, and cerebellum, respectively in wild-type mice (γ8 + / +), and low levels in all regions in knockout (γ8 − / −) mouse brains. In vitro ARG of [18F]JNJ-1 corresponded with IHC staining on adjacent rat brain sections, and the signal being blocked by JNJ-2, a potent and selective antagonist of TARP γ8. In vivo PET imaging demonstrated high brain uptake in the expected areas in rats and monkeys, which was blockable by JNJ-2 in a dose-dependent manner. [18F]JNJ-1 is emerging as a promising PET tracer with high in vitro binding affinity and evidence suggestive of target engagement at AMPAR/TARP γ8. The process of clinical validation is presently underway.
The objective of this study was to evaluate whether retrospectively gated 4D micro-computed tomography (µCT) can quantify extracellular volume fraction (ECV) as an early marker of myocardial fibrosis and remodeling in a high-fat diet (HFD) mouse model, and to determine its relationship with cardiac functional parameters. Male C57BL/6J mice were assigned to control diet or high-fat diet (HFD) groups, with HFD animals imaged after 8 or 16 weeks of feeding and control animals scanned at an age-matched time point. Contrast-enhanced 4D µCT with ECG gating was performed for cardiac function analysis and pre/post-contrast imaging for ECV quantification, corrected for hematocrit. Functional measures included left ventricular (LV) volumes, ejection fraction, mitral annular plane systolic excursion (MAPSE), circumferential shortening, and dobutamine stress response. Global LV ECV significantly increased at 8 weeks of HFD compared to controls, preceding changes in LV mass and ejection fraction. Early ECV elevation correlated with impaired lateral MAPSE, indicating subtle functional impairment despite preserved global systolic function. At 16 weeks, further remodeling was evident with increased LV mass, reduced epicardial circumferential shortening, decreased left atrial ejection area, and diminished dobutamine-induced contractile reserve. Retrospectively gated 4D µCT provides a robust and noninvasive method for early detection of diffuse myocardial fibrosis and functional impairment in small animal models. This approach enables longitudinal studies of cardiac disease progression and therapeutic interventions, offering translational value for preclinical cardiology research.
Diagnosis of Alzheimer’s disease (AD) requires symptoms of dementia and accumulation of amyloid-β (Aβ) and tau in the brain. Molecular imaging of Aβ or tau in AD, though informative, is complicated by the finding that similar changes are found in brains of 30
We investigated the relationship between amyloid deposition in the brain and heart using positron emission tomography (PET) scan with a focus on the influence of the apolipoprotein (Apo) E4 genotype. Twenty-eight participants (12 healthy controls, 11 patients with mild cognitive impairment, and 5 patients with Alzheimer’s disease) were recruited. Each subject visited the institution three times on separate days for echocardiography, brain and cardiac 18F-Florbetaben PET, and brain magnetic resonance imaging. Myocardial tracer retention (MTR,
Visualizing genome organization and transcriptional dynamics with spatial and temporal precision in living cells is essential for elucidating gene regulation and chromatin-associated disease mechanisms, yet conventional methods confront a fundamental tension between endogenous-sequence targeting and live-cell compatibility. Operator–repressor systems require prior insertion of repetitive arrays at engineered loci, whereas fluorescence in situ hybridization mandates cell fixation and thereby precludes temporal analysis. CRISPR–Cas technologies, originally developed for genome editing, have been re-engineered into a versatile molecular-imaging toolkit capable of interrogating native sequences in living cells. Here, we systematically review CRISPR-based live-cell imaging and sensing platforms, critically evaluating their design principles, mechanistic foundations, and performance limitations. We examine dCas9-based DNA labeling, dCas12a systems for non-repetitive loci, Cas13- and Csm-mediated RNA imaging, novel fluorescent reporters, engineered ribonucleoproteins, and delivery innovations including reagent-based Oligo-LiveFISH. To organize this diverse literature, we distinguish three operationally distinct modalities—live-cell imaging, intracellular sensing, and diagnostic biosensing—and assess each platform through three unifying design trade-offs: sensitivity versus cellular perturbation, multiplexing capacity versus system complexity, and detection threshold versus biological fidelity. Building on this framework, we evaluate the integration of CRISPR imaging with super-resolution microscopy, artificial-intelligence-driven computational analysis, and multimodal spatial omics. Collectively, this synthesis clarifies current capabilities, delineates unresolved constraints, and charts a coherent path toward clinically relevant applications of CRISPR-based live-cell molecular imaging.
Despite the potential impact of sorafenib on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-mediated contrast enhancements, attempts to assess these effects are rare. This study aimed to investigate the interaction between Sorafenib and Gd-EOB-DTPA by quantifying the T1 and T2 relaxation times and the relative enhancement rates (RERs) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the liver. The effects on contrast enhancement were assessed using MRI with Chang liver cells and SD rats. MR phantom images were obtained after treating cells with varying dosages of Gd-EOB-DTPA (5, 10 mM) and sorafenib (10, 30 μM) to evaluate MR relaxivities. For the animal study, DCE-MRI was performed following intravenous administration of 25 µmol/kg Gd-EOB-DTPA and two different doses of sorafenib (10, 30 mg/kg). RER was analyzed to evaluate sorafenib's effects on Gd-EOB-DTPA uptake in the liver. Phantom experiments demonstrated alterations in T1 and T2 values, with a tendency towards shortening disrupted by the addition of sorafenib to Gd-EOB-DTPA-treated Chang liver cells. The RERs of DCE-MRI in the liver exhibited a dose-dependent decrease following sorafenib administration, with recovery observed after 4 h. Our results provide quantitative information on sorafenib-mediated interference with Gd-EOB-DTPA-induced contrast enhancement and offer experimental evidence suggesting the possibility of drug-drug interactions between sorafenib and Gd-EOB-DTPA. Although further research is needed to fully elucidate the impact of these interactions, caution is warranted when using these two agents concurrently for liver MRI.
The differential diagnosis of benign and malignant pulmonary nodules is a key problem in clinical diagnosis. Low-dose spiral CT (LDCT) is a commonly used screening method, but it has the limitations of insufficient specificity. There is an urgent need for molecular markers to assist diagnosis. A total of 240 patients with pulmonary nodules were enrolled in this study. The expression of serum miR-760 was detected by polymerase chain reaction (PCR). Receiver operating curve (ROC) was used to evaluate the potential of miR-760 in the diagnosis of lung cancer, and logistic regression analysis was used to evaluate its significance in the risk assessment of lung cancer. Target genes were screened by bioinformatics, protein–protein interaction (PPI) network was constructed, and hub genes were screened. The expression of miR-760 in the lung cancer group was significantly lower than that in the benign group (P < 0.001). Its AUC for differentiating benign and malignant was 0.867. When LDCT combined with miR-760, the area under the curve (AUC) increased to 0.955. Logistic regression analysis showed that miR-760 was a risk factor for lung cancer incidence. PPI network analysis screened 10 hub genes (HMGCR, INSR, CDK6, etc.), which were enriched in cancer related pathways such as HIF-1 and actin cytoskeleton. miR-760 combined with LDCT can significantly improve the differentiation ability of benign and malignant pulmonary nodules, and its mechanism may activate tumor-related signaling pathways by targeting the core genes of PPI network. This study provides a new combination of molecular markers and mechanistic clues for the accurate diagnosis of pulmonary nodules.
To evaluate the efficacy of somatostatin receptor (SSTR)-directed PET/CT in localizing phosphaturic mesenchymal tumors (PMT) in patients with suspected tumor-induced osteomalacia (TIO) and to explore relationships between imaging parameters and biochemical markers. This retrospective analysis included 20 patients with suspected TIO, undergoing SSTR-directed PET/CT. Imaging findings and laboratory markers were assessed. SSTR-positive tumors were resected, while patients without detectable tumor, but persistent renal phosphate wasting, continued on medical treatment. Follow-up assessments included laboratory values and clinical examinations. PMT were detected on PET in 12 patients (60
PurposeMetal chelates play a crucial role in diagnostic imaging and radiotherapy. While gadolinium-based chelates are widely used in MRI, radiometal chelates are increasingly used in nuclear medicine and theranostics. Despite their clinical importance, the extent to which the identity of the coordinated metal influences in vivo chelate pharmacology remains unclear. The goal of this work was to determine whether metal substitution alters transporter-mediated cellular uptake and pharmacological behavior of hepatospecific chelates.ProceduresApo-forms of the clinical hepatospecific MRI contrast agents EOB-DTPA and BOPTA were generated and re-chelated with eight different metals (Sc, Y, Pr, Eu, Gd, Tb, Dy, Ho). In vitro transport of these chelates was assessed in cells expressing rodent and human hepatic transporters. In vivo hepatic uptake was evaluated in mice expressing either wild-type or human hepatic transporters. Tissue distribution and clearance were quantified analytically.ResultsIn vitro uptake of EOB-DTPA and BOPTA chelates by cells expressing rodent and human transporters showed no statistically significant differences across metals. In vivo studies in mice similarly showed no statistically significant differences in hepatic uptake across metals, with the exception of reduced uptake observed for Sc-EOB-DTPA in wild-type animals. No evidence of free metal accumulation in soft tissue was detected. Chelate clearance via renal and hepatobiliary pathways was similar across metals.ConclusionsWithin the class of trivalent metals examined and for EOB-DTPA and BOPTA chelates, transporter-mediated uptake, biodistribution, and clearance were largely independent of metal identity under the conditions tested. These findings support the use of common chelate scaffolds across multiple metals, while highlighting the importance of ligand structure and transporter interactions in governing pharmacology.
A standard imaging strategy for quantifying skeletal muscle perfusion in peripheral artery disease (PAD) does not exist, and the widespread use of PET imaging for this purpose has traditionally been limited by the need for onsite production of short half-life perfusion radioisotopes. Therefore, this study investigated the feasibility of multiparametric PET imaging with commercially available fluorine-18 (18F)-fluorodeoxyglucose (FDG) for the quantification of skeletal muscle perfusion and metabolism in a porcine model of PAD. Eight Yorkshire pigs underwent 60-min dynamic 18F-FDG PET imaging under resting conditions immediately following unilateral surgical ligation of the femoral artery and 2 weeks after arterial occlusion. Calf muscle perfusion was computed using 1-compartment modeling of the first 2.5 min of PET data acquisition, and the metabolic rate of glucose (MRGlu) was computed using 3-compartment modeling of the entire 60-min dataset. Two weeks after arterial occlusion, the gastrocnemius muscle was harvested to compare microvascular density between ischemic and control hindlimbs. Calf perfusion and MRGlu were significantly reduced following peripheral artery occlusion and recovered to control levels 2 weeks later. Recovery of perfusion and metabolism in calf skeletal muscle coincided with a significant increase in calf muscle capillary density 2 weeks after arterial occlusion. This study demonstrates the novel use of dynamic, multiparametric 18F-FDG PET/CT imaging for quantifying ischemia-induced alterations in skeletal muscle perfusion and metabolism, providing a unique comprehensive approach for evaluating PAD pathophysiology and creating opportunities for monitoring treatment responses to emerging therapeutics.
This study aims to quantify and to correct for partial volume effect (PVE) in lymph node metastases of prostate cancer (PC) on Lu-177 SPECT images using 3D-printed phantoms of these structures to establish a ground truth. Ten individuals with clearly delineated, SPECT-positive lymph node metastases were retrospectively selected from a cohort of PC patients undergoing radioligand therapy (RLT). Manual segmentation of the metastases was performed on the CT component. The segmented lymph nodes were 3D-printed as patient-specific lymph node phantoms with volumes ranging from 0.18 to 23.7 ml using a high-resolution 3D printer. These phantoms were filled with Lu-177 and analyzed in a SPECT/CT system to quantify PVE. An exponential curve fit of the recovery coefficient (RC) versus the surface-area to volume ratio (SA:V) was derived from the spheres of a NEMA ICE body phantom and used to correct for PVE in the lymph node phantoms. This method was compared with other post-reconstruction partial volume corrections (PVC). For a tumor to background ratio (TBR) of 10:1 the RCs varied widely, from 82