Molecular imaging of breast cancer

Epilepsy surgery is highly effective in treating refractory epilepsy, but requires accurate presurgical localization of the epileptogenic focus. Briefly, localization of the region of seizure onset traditionally dependents on seizure semiology, scalp EEG recordings and correlation with anatomical imaging modalities such as MRI. The introduction of noninvasive functional neuroimaging methods, including single-photon emission computed tomography (SPECT) and positron emission tomography (PET) has dramatically changed the method for presurgical epilepsy evaluation. These imaging modalities have become powerful tools for the investigation of brain function and are an essential part of the evaluation of epileptic patients. Of these methods, SPECT has the practical capacity to image blood flow functional changes that occur during seizures in the routine clinical setting. In this review we present the basic principles of epilepsy SPECT and PET imaging. We discuss the properties of the SPECT tracers to be used for this purpose and imaging acquisition protocols as well as the diagnostic performance of SPECT in addition to SPECT image analysis methods. This is followed by a discussion and comparison to F-18 FDG PET acquisition and imaging analysis methods.

CLR1404 is a theranostic molecular agent that can be radiolabeled with 124I (CLR 124) for positron emission tomography (PET) imaging, or 131I (CLR 131) for single-photon emission computed tomography (SPECT) imaging and targeted radionuclide therapy. This pilot study evaluated a pretreatment dosimetry methodology in a triple-negative breast cancer patient who was uniquely enrolled in both a CLR 124 PET imaging clinical trial and a CLR 131 therapeutic dose escalation clinical trial. Three-dimensional PET/CT images were acquired at 1, 3, 24, 48, and 120 h postinjection of 178 MBq CLR 124. One month later, pretherapy 2D whole-body planar images were acquired at 0.25, 5, 24, 48, and 144 h postinjection of 370 MBq CLR 131. Following the therapeutic administration of 1990 MBq CLR 131, 3D SPECT/CT images were acquired at 74, 147, 334, and 505 h postinjection. The therapeutic CLR 131 voxel-level absorbed dose was estimated from PET (RAPID PET) and SPECT (RAPID SPECT) images using a Geant4-based Monte Carlo dosimetry platform called RAPID (Radiopharmaceutical Assessment Platform for Internal Dosimetry), and region of interest (ROI) mean doses were also estimated using the OLINDA/EXM software based on PET (OLINDA PET), SPECT (OLINDA SPECT), and planar (OLINDA planar) images. The RAPID PET and OLINDA PET tracer-predicted ROI mean doses correlated well (m ≥ 0.631, R2 ≥ 0.694, p ≤ 0.01) with both the RAPID SPECT and OLINDA SPECT therapeutic mean doses. The 2D planar images did not have any significant correlations. The ROI mean doses differed by -4% to -43% between RAPID and OLINDA/EXM, and by -19% to 29% between PET and SPECT. The 3D dose distributions and dose volume histograms calculated with RAPID were similar for the PET/CT and SPECT/CT. This pilot study demonstrated that CLR 124 pretreatment PET images can be used to predict CLR 131 3D therapeutic dosimetry better than CLR 131 2D planar images. In addition, unlike OLINDA/EXM, Monte Carlo dosimetry methods were capable of accurately predicting dose heterogeneity, which is important for predicting dose-response relationships and clinical outcomes.

The single photon emission computed tomography (SPECT) radiotracer [123I]iomazenil is used to assess benzodiazepine receptor binding parameters. These measurements are relative indices of benzodiazepine receptor concentration (B'max). To evaluate the ability of such indices in accurately accessing the B'max the authors compared them with absolute values of B'max, measured using positron emission tomography (PET). The authors performed SPECT, PET, and magnetic resonance imaging (MRI) studies on a group composed of seven subjects. For SPECT studies, the authors administered a single injection of [123I]iomazenil and estimated the total and specific distribution volumes (DV(T SPECT), DV(S SPECT)) and the binding potential (BP) using unconstrained (BP(SPECT)) and constrained (BP(C SPECT)) compartmental models. For PET studies, the authors used a multiinjection approach with [11C]flumazenil and unlabeled flumazenil to estimate absolute values of receptor concentration, B'max, and some other binding parameters. The authors studied the correlation of different binding parameters with B'max. To study the robustness of the binding parameter measurements at the pixel level, the authors applied a wavelet-based filter to improve signal-to-noise ratio of time-concentration curves, and the calculated kinetic parameters were used to build up parametric images. For PET data, the B'max and the DV(PET) were highly correlated (r = 0.988). This confirms that it is possible to use the DV(PET) to access benzodiazepine receptor density. For SPECT data, the correlation between DV(SPECT) estimated using a two- and three-compartment model was also high (r = 0.999). The DV(T SPECT) and BP(C SPECT) parameters estimated with a constrained three-compartment model or the DV(T''SPECT) parameter estimated with a two-compartment model were also highly correlated to the B'max parameter estimated with PET. Finally, the robustness of the binding parameters allowed the authors to build pixel-by-pixel parametric images using SPECT data.

ObjectiveDeep learning approaches have attracted attention for improving the scoring accuracy in computed tomography-less single photon emission computed tomography (SPECT). In this study, we proposed a novel deep learning approach referring to positron emission tomography (PET). The aims of this study were to analyze the agreement of representative voxel values and perfusion scores of SPECT-to-PET translation model-generated SPECT (SPECTSPT) against PET in 17 segments according to the American Heart Association (AHA).MethodsThis retrospective study evaluated the patient-to-patient stress, resting SPECT, and PET datasets of 71 patients. The SPECTSPT generation model was trained (stress: 979 image pairs, rest: 987 image pairs) and validated (stress: 421 image pairs, rest: 425 image pairs) using 31 cases of SPECT and PET image pairs using an image-to-image translation network. Forty of 71 cases of left ventricular base-to-apex short-axis images were translated to SPECTSPT in the stress and resting state (stress: 1830 images, rest: 1856 images). Representative voxel values of SPECT and SPECTSPT in the 17 AHA segments against PET were compared. The stress, resting, and difference scores of 40 cases of SPECT and SPECTSPT were also compared in each of the 17 segments.ResultsFor AHA 17-segment-wise analysis, stressed SPECT but not SPECTSPT voxel values showed significant error from PET at basal anterior regions (segments #1, #6), and at mid inferoseptal regions (segments #8, #9, and #10). SPECT, but not SPECTSPT, voxel values at resting state showed significant error at basal anterior regions (segments #1, #2, and #6), and at mid inferior regions (segments #8, #9, and #11). Significant SPECT overscoring was observed against PET in basal-to-apical inferior regions (segments #4, #10, and #15) during stress. No significant overscoring was observed in SPECTSPT at stress, and only moderate over and underscoring in the basal inferior region (segment #4) was found in the resting and difference states.ConclusionsOur PET-supervised deep learning model is a new approach to correct well-known inferior wall attenuation in SPECT myocardial perfusion imaging. As standalone SPECT systems are used worldwide, the SPECTSPT generation model may be applied as a low-cost and practical clinical tool that provides powerful auxiliary information for the diagnosis of myocardial blood flow.

Accurate determination of tumor human epidermal growth factor receptor 2 (HER2)-status in breast cancer patients is possible via noninvasive imaging, provided adequate tracers are used. In this study, we describe the generation of a panel of 38 nanobodies, small HER2-binding fragments that are derived from heavy-chain-only antibodies raised in an immunized dromedary. In search of a lead compound, a subset of nanobodies was biochemically characterized in depth and preclinically tested for use as tracers for imaging of xenografted tumors. The selected compound, 2Rs15d, was found to be stable and to interact specifically with HER2 recombinant protein and HER2-expressing cells in ELISA, surface plasmon resonance, flow cytometry, and radioligand binding studies with low nanomolar affinities, and did not compete with anti-HER2 therapeutic antibodies trastuzumab and pertuzumab. Single-photon-emission computed tomography (SPECT) imaging quantification and biodistribution analyses showed that (99m)Tc-labeled 2Rs15d has a high tumor uptake in 2 HER2(+) tumor models, fast blood clearance, low accumulation in nontarget organs except kidneys, and high concomitant tumor-to-blood and tumor-to-muscle ratios at 1 h after intravenous injection. These values were dramatically lower for an irrelevant control (99m)Tc-nanobody and for (99m)Tc-2Rs15d targeting a HER2(-) tumor.

Phase I Study of Noninvasive Imaging of Adenovirus-mediated Gene Expression in the Human Prostate

Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are non-invasive nuclear medicine techniques that can identify areas of abnormal myocardial perfusion. We assessed the prevalence of cardiovascular risk factors in patients with suspected coronary artery disease (CAD) undergoing SPECT or PET stress myocardial perfusion imaging (MPI). Based on significant risk factors associated with an abnormal MPI, we developed a nomogram for each cohort as a pretest that would be helpful in decision-making for clinicians. A total of 6,854 patients with suspected CAD who underwent stress myocardial perfusion imaging by SPECT or PET/CT was studied. As part of the baseline examination, clinical teams collected information on traditional cardiovascular risk factors: age, gender, body mass index, angina, dyspnea, diabetes, hypertension, hyperlipidemia, family history of CAD, and smoking. The prevalence of cardiovascular risk factors was different in the two cohorts of patients undergoing SPECT (n = 4,397) or PET (n = 2,457) myocardial perfusion imaging. A statistical significance was observed in both cohorts for age, gender, and diabetes. At multivariable analysis, only age and male gender were significant covariates in both cohorts. The risk of abnormal myocardial perfusion imaging related to age was greater in patients undergoing PET (odds ratio 4% vs. 1% per year). In contrast, male gender odds ratio was slightly higher for SPECT compared to PET (2.52 vs. 2.06). In the SPECT cohort, smoking increased the risk of abnormal perfusion of 24%. Among patients undergoing PET, diabetes and hypertension increased the risk of abnormal perfusion by 63% and 37%, respectively. For each cohort, we obtained a nomogram by significant risk factors at multivariable logistic regression. The area under the receiver operating characteristic curve associated with the nomogram was 0.67 for SPECT and 0.73 for the PET model. Patients with suspected CAD belonging to two different cohorts undergoing SPECT or PET stress myocardial perfusion imaging can have different cardiovascular risk factors associated with a higher risk of an abnormal MPI study. As crude variables, age, gender, and diabetes were significant for both cohorts. Net of the effect of other covariates, age and gender were the only risk factors in common between the two cohorts. Furthermore, smoking and type of stress test were significant for the SPECT cohort, where as diabetes and hypertension were significant for the PET cohort. Nomograms obtained by significant risk factors for the two cohorts can be used by clinicians to evaluate the risk of an abnormal study.

PET and SPECT in epilepsy: A critical review

Prostate cancer (PCa) is the second leading cause of cancer deaths in American men. Early detection of PCa by blood tests for elevated levels of prostate-specific-antigen (PSA) has lead to early treatment and a reduction in death rates. However, PSA level alone does not distinguish between PCa and normal conditions that cause elevated PSA. Furthermore, because PCa can be a very slow growing cancer, even confirmation of PCa cells in a biopsy gives no indication whether the PCa will progress into active disease within the individual's lifetime. As a result many patients receive treatment that they may not need. Imaging is an attractive modality for the detection and characterization of disease because most techniques are non- or minimally invasive, nondestructive, provide dynamic real-time data, and allow for repeat measurements. In PCa, advanced imaging techniques could be useful for accurate staging of primary disease, restaging of recurrent disease, detection of metastatic lesions, and predicting the aggressiveness of the disease. This paper reviews the radionuclide based imaging agents for planar, single photon emission computed tomography (SPECT), and positron emission tomography (PET) imaging currently used in the clinic and those under development for PCa. The former includes the bone agents technetium diphosphonates and F-18 fluoride, the metabolic agents 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG), and receptor targeted radiolabeled monoclonal antibodies including ProstaScint. The latter agents include C-11 acetate, C-11 and F-18 choline, C-11 and F-18 labeled 1-aminocyclobutane-1-carboxylic acid, radiolabeled androgen receptor binding compounds, radiolabeled peptides and small molecules for receptors over expressed either on prostate cancer itself or on the associated tumor neovasculature. Coregistration of PET or SPECT images with CT or MRI scans, improvements in imaging cameras, and image reconstruction algorithms have improved the quality of the images to the point where dual modality (radionuclide/CT or MRI) imaging with several agents can now be considered for staging of PCa. In addition, the high selectivity and rapid localization of many of the new agents under development portends promise for a greater use of radionuclide imaging for prostate cancer detection, characterization, and treatment monitoring.

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional nuclear medicine techniques which allow for accurate non-invasive in vivo measurements of a wide range of regional tissue functions in man. Brain functional imaging with SPECT and PET is based on the recording of the distribution of administered radionuclides in three dimensions, thus producing maps of brain biochemical and physiological processes. SPECT and PET techniques are able to image brain perfusion and metabolism, as well as various neurotransmission or other cellular processes using specific radioligands which mark in vivo receptors, transporters or enzymes. Brain SPECT and PET imaging or molecular imaging -, has been applied to the study of Alzheimer’s disease (AD) for over two decades. These functional neuroimaging approaches have the capability of identifying subtle pathophysiologic changes in the brain before structural changes are present (Xu et al., 2000). Therefore they possess greater potential for accurate and early diagnosis, monitoring disease progression, and better treatment followup. Furthermore, the application of SPECT and PET techniques to the study of AD has led to increased understanding of the underlying pathology and the disease processes and improved the differential diagnosis from other neurodegenerative causes of dementia.

Low spatial resolution and the related partial volume effects limit the diagnostic potential of brain single photon emission computed tomography (SPECT) imaging. As a possible remedy for this problem we propose a technique for the fusion of SPECT and MR images, which requires for a given patient the SPECT data and the T1-weighted MR image. Basically, after the reconstruction and coregistration steps, the high-frequency part of the MR, which would be unrecoverable by the set SPECT acquisition system + reconstruction algorithm, is extracted and added to the SPECT image. The tuning of the weight of the MR on the resulting fused image can be performed very quickly, any iterative reconstruction algorithm can be used and, in the case that the SPECT projections are not available, the proposed technique can also be applied directly to the SPECT image, provided that the performance of the scanner is known. The procedure has the potential of increasing the diagnostic value of a SPECT image. Even in the locations of SPECT-MR mismatch it does not significantly affect quantitation over regions of interest (ROIs) whose dimensions are decidedly larger than the SPECT resolution distance. On the other hand, appreciable corrections for partial volume effects are expected in the locations where the contrast in the structural MR matches the corresponding contrast in functional activity.

Practical assessment of myocardial viability with a positron coincidence gamma camera using 18F-fluorodeoxyglucose in acute myocardial infarction: Comparison with dedicated positron emission tomography and 201Tl single photon emission computed tomography

Multimodality nuclear medicine imaging in three-dimensional radiation treatment planning for lung cancer: challenges and prospects

to assess diagnostic capabilities of single-photon emission computed tomography (SPECT) in the detection of obstructive coronary artery (CA) lesions, depending on the meeting appropriate use criteria. We used in this retrospective analysis data from 107 patients with previously diagnosed ischemic heart disease (IHD) or in need to exclude it, who were hospitalized in inpatient departments of the Research Institute for Complex Issues of Cardiovascular Diseases in the period from 2012 to 2015. All patients underwent coronary angiography (CAG) and SPECT (the time interval between the studies did not exceed 3 months) for detection of hemodynamically significant CA stenoses. Patients were distributed into two groups according SPECT imaging appropriateness score: group 1-88 patients with score 7-9 (in whom SPECT imaging was appropriate), group 2-19 patients with score 1-6 (in whom SPECT imaging was uncertain, possibly appropriate, or inappropriate. Clinical signs and symptoms of angina pectoris were predominantly found in group 1 patients (p=0.499). Asymptomatic patients were more likely to be found in group 2 (p<0.001). Group 1 patients commonly had high pretest probability (PTP) (over 90 %, p<0.001), whereas group 2 patients commonly had low PTP (5-10 %, p<0.001). Mean PTP was 77 and 58 % in groups 1 and 2, respectively (p=0.003). According to positive SPECT imaging, significant CA lesions were more often found in group 1 compared to group 2 (31.8 and 10.5 %, respectively, p=0.060). Two- and three-vessel disease prevailed in group 1 (25 % and 14.7 %) according the analysis of prevalence and location of hemodynamically significant CA lesions, although the data did not reach statistical significance (p=0.057 and p=0.073). Stenoses >70 % were more commonly detected in group 1, compared to group 2: in anterior descending artery 52.3 vs. 5.3 % (p<0.001), circumflex artery 35.2 vs. 10.5 %; (p=0.034), right coronary artery 34.1 vs. 10.5 % (p=0.041). The sensitivity in both groups was rather low (40 % vs. 25 %), whereas specificity was 83 % in group 1 and 93 % in group 2. According to clinical examination, patients with IHD and indications for SPECT imaging more often had obstructive CA lesions (63.6 %), than patients with questionable or no indications (21.1 %). However, rate of positive findings during stress tests with SPECT imaging was low in both groups and did not differ significantly (p=0.06). Despite high specificity of SPECT imaging, its sensitivity was low in both groups.

Brain perfusion single photon emission computed tomography (SPECT) scans were initially developed in 1970's. A key radiopharmaceutical, hexamethylpropyleneamine oxime (HMPAO), was originally approved in 1988, but was unstable. As a result, the quality of SPECT images varied greatly based on technique until 1993, when a method of stabilizing HMPAO was developed. In addition, most SPECT perfusion studies pre-1996 were performed on single-head gamma cameras. In 1996, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (TTASAAN) issued a report regarding the use of SPECT in the evaluation of neurological disorders. Although the TTASAAN report was published in January 1996, it was approved for publication in October 1994. Consequently, the reported brain SPECT studies relied upon to derive the conclusions of the TTASAAN report largely pre-date the introduction of stabilized HMPAO. While only 12% of the studies on traumatic brain injury (TBI) in the TTASAAN report utilized stable tracers and multi-head cameras, 69 subsequent studies with more than 23,000 subjects describe the utility of perfusion SPECT scans in the evaluation of TBI. Similarly, dementia SPECT imaging has improved. Modern SPECT utilizing multi-headed gamma cameras and quantitative analysis has a sensitivity of 86% and a specificity of 89% for the diagnosis of mild to moderate Alzheimer's disease—comparable to fluorodeoxyglucose positron emission tomography. Advances also have occurred in seizure neuroimaging. Lastly, developments in SPECT imaging of neurotoxicity and neuropsychiatric disorders have been striking. At the 25-year anniversary of the publication of the TTASAAN report, it is time to re-examine the utility of perfusion SPECT brain imaging. Herein, we review studies cited by the TTASAAN report vs. current brain SPECT imaging research literature for the major indications addressed in the report, as well as for emerging indications. In Part II, we elaborate technical aspects of SPECT neuroimaging and discuss scan interpretation for the clinician.