Molecular imaging in oncology: Current impact and future directions.

The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging-particularly when combined with liquid biopsy for screening purposes-promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology.

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: The extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome. METHODS: Consecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body planar and cardiac single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre and 4 Italian centers were included. Cardiac uptake was defined according to the Perugini classification: 0=absent cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=high uptake greater than bone. Extent of right ventricular (RV) uptake was defined as focal (basal segment of the RV free wall only) or diffuse (extending beyond basal segment) on the basis of SPECT imaging. The primary outcome was all-cause mortality. RESULTS: Among 1422 patients with ATTR-CM, RV uptake accompanying left ventricular uptake was identified by SPECT imaging in 100% of cases at diagnosis. Median follow-up in the whole cohort was 34 months (interquartile range, 21 to 50 months), and 494 patients died. By Kaplan-Meier analysis, diffuse RV uptake on SPECT imaging (n=936) was associated with higher all-cause mortality compared with focal (n=486) RV uptake (77.9% versus 22.1%; P<0.001), whereas Perugini grade was not associated with survival (P=0.27 in grade 2 versus grade 3). On multivariable analysis, after adjustment for age at diagnosis (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), presence of the p.(V142I) TTR variant (HR, 1.42 [95% CI, 1.20-1.81]; P=0.004), National Amyloidosis Centre stage (each category, P<0.001), stroke volume index (HR, 0.99 [95% CI, 0.97-0.99]; P=0.043), E/e' (HR, 1.02 [95% CI, 1.007-1.03]; P=0.004), right atrial area index (HR, 1.05 [95% CI, 1.02-1.08]; P=0.001), and left ventricular global longitudinal strain (HR, 1.06 [95% CI, 1.03-1.09]; P<0.001), diffuse RV uptake on SPECT imaging (HR, 1.60 [95% CI, 1.26-2.04]; P<0.001) remained an independent predictor of all-cause mortality. The prognostic value of diffuse RV uptake was maintained across each National Amyloidosis Centre stage and in both wild-type and hereditary ATTR-CM (P<0.001 and P=0.02, respectively). CONCLUSIONS: Diffuse RV uptake of bone tracer on SPECT imaging is associated with poor outcomes in patients with ATTR-CM and is an independent prognostic marker at diagnosis.

Preclinical ImmunoPET Imaging Using a Zr-89-Labeled Anti-CD146 Monoclonal Antibody for Diagnosis of Melanoma.

The aim of this study was to evaluate the preclinical efficacy of [89Zr]Zr-DFO-Ab253 as a novel positron emission tomography (PET) tracer for CD146-positive malignant melanoma imaging. Considering the high expression of CD146 in malignant melanoma, this study investigated the effect of different CD146 expression levels on the tumor uptake of [89Zr]Zr-DFO-Ab253. CD146 selectivity was investigated by using the CD146-positive human melanoma cell A375 and the CD146-negative human alveolar epithelial cell A549. The cell uptake of [89Zr]Zr-DFO-Ab253 tracers was investigated, and receptor-binding affinities were measured by radioactive enzyme-linked immunosorbent assay. Biodistribution studies and micro-PET imaging of the radiotracers were performed on mice bearing A375 and A549 xenografts under baseline and blocking conditions. An immunohistochemical test was performed using A375 and A549 tissue sections for CD146 expression level analysis. [89Zr]Zr-DFO-Ab253 was obtained with a high radiochemical yield (87.86 ± 4.66%) and a satisfactory radiochemical purity (>98.0%). The specificity and affinity of [89Zr]Zr-DFO-Ab253 were confirmed in melanoma A375 cells and in vivo PET imaging of A375 tumor models. [89Zr]Zr-DFO-IgG and A549 lung tumors were prepared as control radiotracers and negative models to verify the specificity of [89Zr]Zr-DFO-Ab253 on CD146. [89Zr]Zr-DFO-Ab253 has a Kd of 4.01 ± 0.50 nM. PET imaging and biodistribution showed a higher uptake of [89Zr]Zr-DFO-Ab253 in A375 melanomas than that in A549 tumors (42.1 ± 4.04% vs 7.87 ± 1.30% ID/g at 120 h, P < 0.05). A low tumor uptake of [89Zr]Zr-DFO-IgG was observed with uptakes of 1.91 ± 0.41 and 2.80 ± 0.14 ID%/g when blocked at 120 h. The radiation-absorbed dose was calculated to be 0.13 mSv/MBq. This study demonstrates the synthesis and preclinical evaluation of [89Zr]Zr-DFO-Ab253 and indicates that the novel tracer has promising applications in malignant melanoma-specific PET imaging because of its high uptake and long-time retention in malignant melanoma. It also provides feasibility for the development of integrated molecular probes for diagnosis and treatment based on the CD146 target.

Feasibility Study of Single-Photon Emission Computed Tomography with Iodine-123 Labeled Metaiodobenzylguanidine for Preclinical Evaluation of Labetalol as a ß-Adrenergic Receptor Blocker.

Among clinically used radiopharmaceuticals, iodine-123 labeled metaiodobenzylguanidine ([123I]mIBG) serves for diagnosing neuroendocrine tumors and obtaining images of myocardial sympathetic innervation. mIBG, a structural analogue of norepinephrine (NE), a neurotransmitter acting in peripheral and central nerves, follows a pathway similar to NE, transmitting signals through the NE transporter (NET) located at synaptic terminals. It moves through the body without decomposing, enabling noninvasive image evaluation. In this study, we aimed to quantify [123I]mIBG uptake in the adrenal glands using small animal single-photon emission computed tomography/computed tomography (SPECT/CT) images post [123I]mIBG administration. We investigated the possibility of assessing the effectiveness of ß-adrenergic receptor blockers by quantifying SPECT/CT images and biodistribution results to determine the degree of [123I]mIBG uptake in the adrenal glands treated with labetalol, a known ß-adrenergic receptor blocker. Upon intravenous administration of [123I]mIBG to mice, SPECT/CT images were acquired over time to confirm the in vivo distribution pattern, revealing a clear uptake in the adrenal glands. Labetalol inhibited the uptake of [123I]mIBG in cell lines expressing NET. A decrease in [123I]mIBG uptake in the adrenal glands was observed in the labetalol-treated group compared with the normal group through SPECT/CT imaging and biodistribution studies. These results demonstrate that SPECT/CT imaging with [123I]mIBG could be applicable for evaluating the preclinical efficacy of new antihypertensive drug candidates such as labetalol, a ß-adrenergic receptor blocker.

Artificial intelligence in immunotherapy PET/SPECT imaging.

OBJECTIVE: Immunotherapy has dramatically altered the therapeutic landscape for oncology, but more research is needed to identify patients who are likely to achieve durable clinical benefit and those who may develop unacceptable side effects. We investigated the role of artificial intelligence in PET/SPECT-guided approaches for immunotherapy-treated patients. METHODS: We performed a scoping review of MEDLINE, CENTRAL, and Embase databases using key terms related to immunotherapy, PET/SPECT imaging, and AI/radiomics through October 12, 2022. RESULTS: Of the 217 studies identified in our literature search, 24 relevant articles were selected. The median (interquartile range) sample size of included patient cohorts was 63 (157). Primary tumors of interest were lung (n = 14/24, 58.3%), lymphoma (n = 4/24, 16.7%), or melanoma (n = 4/24, 16.7%). A total of 28 treatment regimens were employed, including anti-PD-(L)1 (n = 13/28, 46.4%) and anti-CTLA-4 (n = 4/28, 14.3%) monoclonal antibodies. Predictive models were built from imaging features using univariate radiomics (n = 7/24, 29.2%), radiomics (n = 12/24, 50.0%), or deep learning (n = 5/24, 20.8%) and were most often used to prognosticate (n = 6/24, 25.0%) or describe tumor phenotype (n = 5/24, 20.8%). Eighteen studies (75.0%) performed AI model validation. CONCLUSION: Preliminary results suggest broad potential for the application of AI-guided immunotherapy management after further validation of models on large, prospective, multicenter cohorts. CLINICAL RELEVANCE STATEMENT: This scoping review describes how artificial intelligence models are built to make predictions based on medical imaging and explores their application specifically in the PET and SPECT examination of immunotherapy-treated cancers. KEY POINTS: • Immunotherapy has drastically altered the cancer treatment landscape but is known to precipitate response patterns that are not accurately accounted for by traditional imaging methods. • There is an unmet need for better tools to not only facilitate in-treatment evaluation but also to predict, a priori, which patients are likely to achieve a good response with a certain treatment as well as those who are likely to develop side effects. • Artificial intelligence applied to PET/SPECT imaging of immunotherapy-treated patients is mainly used to make predictions about prognosis or tumor phenotype and is built from baseline, pre-treatment images. Further testing is required before a true transition to clinical application can be realized.

ESR Essentials: imaging in stable chest pain - practice recommendations by ESCR.

Stable chest pain is a common symptom with multiple potential causes. Non-invasive imaging has an important role in diagnosis and guiding management through the assessment of coronary stenoses, atherosclerotic plaque, myocardial ischaemia or infarction, and cardiac function. Computed tomography (CT) provides the anatomical evaluation of coronary artery disease (CAD) with the assessment of stenosis, plaque type and plaque burden, with additional functional information available from CT fractional flow reserve (FFR) or CT myocardial perfusion imaging. Stress magnetic resonance imaging, nuclear stress myocardial perfusion imaging, and stress echocardiography can assess myocardial ischaemia and other cardiac functional parameters. Coronary CT angiography can be used as a first-line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. Functional testing may be considered for patients with known CAD, where the clinical significance is uncertain based on anatomical testing, or in patients with high pre-test probability. This practice recommendations document can be used to guide the selection of non-invasive imaging for patients with stable chest pain and provides brief recommendations on how to perform and report these diagnostic tests. KEY POINTS: The selection of non-invasive imaging tests for patients with stable chest pain should be based on symptoms, pre-test probability, and previous history. Coronary CT angiography can be used as a first-line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. Functional testing can be considered for patients with known CAD, where the clinical significance of CAD is uncertain based on anatomical testing, or in patients with high pre-test probability. KEY RECOMMENDATIONS: Non-invasive imaging is an important part of the assessment of patients with stable chest pain. The selection of non-invasive imaging test should be based on symptoms, pre-test probability, and previous history. (Level of evidence: High). Coronary CT angiography can be used as a first line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. CT provides information on stenoses, plaque type, plaque volume, and if required functional information with CT fractional flow reserve or CT perfusion. (Level of evidence: High). Functional testing can be considered for patients with known CAD, where the clinical significance of CAD is uncertain based on anatomical testing, or in patients with high pre-test probability. Stress MRI, SPECT, PET, and echocardiography can provide information on myocardial ischemia, along with cardiac functional and other information. (Level of evidence: Medium).

Single-Photon Emission Computed Tomography/Computed Tomography Utilization for Extremity Melanomas at a High-Volume Center.

INTRODUCTION: Planar lymphoscintigraphy (PL) is commonly used in mapping before sentinel lymph node biopsy (SLNB) for invasive cutaneous melanoma. Recently, single-photon emission computed tomography (SPECT)/ computed tomography (CT) has been utilized, in addition to PL, for detailed anatomic information and detection of sentinel lymph nodes (SLNs) outside of the primary nodal basin in truncal and head and neck melanoma. Following a protocol change due to COVID-19, our institution began routinely obtaining both PL and SPECT-CT imaging for all melanoma SLN mapping. We hypothesized that SPECT-CT is associated with higher instances of SLNBs from "nontraditional" nodal basins (NTNB) for extremity melanomas. METHODS: Patients with extremity melanoma (2017-2022) who underwent SLNB were grouped into SPECT-CT with PL versus PL alone. Outcomes were total SLNs removed, + or-SLN status, total NTNB sampled, and postoperative complication rate. Poisson regression and logistic regression models were used to assess association of SPECT-CT with patient outcomes. RESULTS: Of 380 patients with extremity melanoma, 42.11% had SPECT-CT. There were no differences between the groups with regards to age at diagnosis or sex. From 2020 to 2022, all patients underwent SPECT-CT. SPECT-CT was associated with increased odds of SLNB from an NTNB, (odds ratio = 2.39 [95% confidence interval: 1.25-4.67]). There was no difference in odds of number of SLNs sampled, SLN positivity rate, or postoperative complication rate with SPECT-CT. CONCLUSIONS: Routine SPECT-CT was associated with higher incidence of SLNB in NTNB but did not increase number of SLNs removed or SLN positivity rate. The added value of routine SPECT-CT in cutaneous melanoma of the extremities remains to be defined.

Cardiac positron emission tomography and other modalities for coronary artery disease assessment: A snapshot from the medicare data.

BACKGROUND: Positron emission tomography (PET) is an important tool for assessing coronary artery disease (CAD), but its widespread utilization is limited due to various factors, including limited local champion availability. This study aims to compare the frequency of PET procedures and their interpreters with other common CAD assessment modalities. METHODS: Using Medicare data, we examined the number of cardiac PET procedures billed and compared them with single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA), stress magnetic resonance imaging (MRI), and stress echocardiography. Healthcare Common Procedure Coding System codes were used to identify procedures. We calculated the total number of PET myocardial perfusion imaging (MPI) procedures, the proportion of PET/CT and myocardial blood flow (MBF) assessments, and the median number of studies read per physician. We also analyzed the trends in the use of different CAD assessment modalities between 2018 and 2022. Descriptive statistics summarized the data. RESULTS: In 2022, Medicare billed for 212,106 PET MPI scans. SPECT was six times more frequent (1,343,519), whereas stress echocardiography (201,676) and CCTA (118,734) had similar or lower use. Stress MRI (3,932) was least used. Of the PET MPI scans, 46% were PET/CT, and 39% included MBF measurements. Cardiologists interpreted 86% of PET scans, with a median of 58 studies per reader; 23% interpreted ≤25 studies annually. SPECT had a median of 63 studies per reader, and CCTA, stress MRI, and stress echocardiography had medians of 27, 20, and 24, respectively. PET, CT, and MRI use increased from 2018 to 2022, whereas SPECT and stress echocardiography declined. CONCLUSION: In the Medicare population, radionuclide perfusion imaging (SPECT and PET) remained the preferred method for assessment of CAD, with SPECT being the most frequently used modality and PET being the second most frequently used modality for this application. However, PET/CT and MBF are underutilized, limiting diagnostic and prognostic capabilities. Efforts to enhance education and awareness of PET's advantages and to address barriers to its wider adoption are essential to maximize its clinical benefits and improve patient outcomes.

Utility of combining multiple parameters of 123I-IMP SPECT and voxel-based morphometry MRI using a multiparametric scoring system for differentiating dementia with Lewy bodies from Alzheimer's disease.

BACKGROUND: Brain magnetic resonance imaging voxel-based morphometry (VBM) and perfusion single-photon emission computed tomography (SPECT) are useful for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). PURPOSE: To determine whether combining multiple parameters of VBM and SPECT using a multiparametric scoring system (MSS) improves diagnostic accuracy in differentiating DLB from AD. MATERIAL AND METHODS: In total, 23 patients with DLB and 57 patients with AD underwent imaging using a voxel-based specific regional analysis system for AD (VSRAD), an easy Z-score imaging system, and a Z-Graph using three-dimensional stereotactic surface projection. The cutoff values were determined using the receiver operating characteristic curve to differentiate DLB from AD for all parameters. Patients were scored 1 (DLB) or 0 (AD) for each statistically significant parameter, according to a threshold. The total score was determined for each case to obtain a cutoff value for the MSS. RESULTS: The mean Z-scores in the medial temporal lobes using the VSRAD were significantly lower in patients with DLB than in those with AD. Each Z-score of the summed Z-scores in all four segmented regions of the occipital lobes using the Z-Graph was significantly higher in patients with DLB than in those with AD. Among the five parameters, the highest accuracy was 80% for the Z-score of the summed Z-scores in the left medial occipital lobe. For the MSS, a cutoff value of four improved the diagnostic accuracy to 82%. CONCLUSION: MSS was more accurate than any single parameter of VBM or SPECT in differentiating DLB from AD.

Predicting event-free survival after induction of remission in high-risk pediatric neuroblastoma: combining 123I-MIBG SPECT-CT radiomics and clinical factors.

BACKGROUND: Accurately quantifying event-free survival after induction of remission in high-risk neuroblastoma can lead to better subsequent treatment decisions, including whether more aggressive therapy or milder treatment is needed to reduce unnecessary treatment side effects, thereby improving patient survival. OBJECTIVE: To develop and validate a 123I-metaiodobenzylguanidine (MIBG) single-photon emission computed tomography-computed tomography (SPECT-CT)-based radiomics nomogram and evaluate its value in predicting event-free survival after induction of remission in high-risk neuroblastoma. MATERIALS AND METHODS: One hundred and seventy-two patients with high-risk neuroblastoma who underwent an 123I-MIBG SPECT-CT examination were retrospectively reviewed. Eighty-seven patients with high-risk neuroblastoma met the final inclusion and exclusion criteria and were randomized into training and validation cohorts in a 7:3 ratio. The SPECT-CT images of patients were visually analyzed to assess the Curie score. The 3D Slicer software tool was used to outline the region of interest of the lumbar 3-5 vertebral bodies on the SPECT-CT images. Radiomics features were extracted and screened, and a radiomics model was constructed with the selected radiomics features. Univariate and multivariate Cox regression analyses were used to determine clinical risk factors and construct the clinical model. The radiomics nomogram was constructed using multivariate Cox regression analysis by incorporating radiomics features and clinical risk factors. C-index and time-dependent receiver operating characteristic curves were used to evaluate the performance of the different models. RESULTS: The Curie score had the lowest efficacy for the assessment of event-free survival, with a C-index of 0.576 and 0.553 in the training and validation cohorts, respectively. The radiomics model, constructed from 11 radiomics features, outperformed the clinical model in predicting event-free survival in both the training cohort (C-index, 0.780 vs. 0.653) and validation cohort (C-index, 0.687 vs. 0.667). The nomogram predicted the best prognosis for event-free survival in both the training and validation cohorts, with C-indices of 0.819 and 0.712, and 1-year areas under the curve of 0.899 and 0.748, respectively. CONCLUSION: 123I-MIBG SPECT-CT-based radiomics can accurately predict the event-free survival of high-risk neuroblastoma after induction of remission The constructed nomogram may enable an individualized assessment of high-risk neuroblastoma prognosis and assist clinicians in optimizing patient treatment and follow-up plans, thereby potentially improving patient survival.