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Revolutionizing medical diagnosis with SPECT imaging: Clinical applications of a nuclear imaging technology

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Abstract

Nuclear medicine uses radioactive probes, commonly referred to as radiotracers, for the diagnosis and treatment of diseases. As of today, single photon emission computed tomography (SPECT) has revolutionized the field of nuclear imaging and is one of the most important medical imaging methods providing functional information about physiologic and pathologic processes in biologic systems. In contrast to other imaging modalities used in clinical diagnosis, SPECT reveals information based on the spatial concentration of injected radiopharmaceutics. SPECT functional imaging provides increased sensitivity, improved contrast, reduced structural noise, and precise localization of defects. Functional imaging, however, has low specificity in distinctly different pathologies (e.g., degenerative, inflammatory, or malignant bone lesions) and limited spatial and temporal resolution. To overcome this disadvantage, highly specific probes (e.g., receptor imaging) have been developed for targeted clinical imaging. SPECT has found its way into most clinical scenarios in patients with endocrine tumors, neuroendocrine tumors, lung cancers, brain tumors, lymphoma, prostate cancer, and malignant bone lesions. Furthermore, hybrid SPECT/CT imaging is especially suited to support the increasing applications of minimally invasive surgery, as well as to precisely define the diagnostic and prognostic profile of cardiovascular patients. This chapter details the historical origins of emission tomography, basic principles of SPECT imaging, the current status of SPECT instrumentation and imaging, and a broad spectrum of clinical applications in the diagnosis of malignant diseases such as cancer.

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BACKGROUND Prostate carcinoma poses a significant public health problem. Although a minority of men with newly diagnosed prostate carcinoma manifest bone metastases or skeletal abnormalities, a significant proportion of men will develop these complications over the course of their lives. Patients at highest risk for bone metastases include those with high grade, high stage neoplasms, those who fail primary curative therapies such as radical prostatectomy or radiation therapy, and those who develop biochemical recurrence after hormonal therapy.METHODS The relative risks and prognostic factors for bone metastases in each of these settings will be reviewed.RESULTSIn comparison with men without prostate carcinoma, benign skeletal complications (osteopenia and fractures) occur at significantly increased rates among men with untreated prostate carcinoma. Moreover, the incidence rate of these conditions increases dramatically among those men who are receiving endocrine therapy. The duration and intensity of the endocrine therapy may be associated with the incidence rate and severity of skeletal complications.CONCLUSIONS Given the significant incidence rate and quality of life implications of skeletal complications and bone metastases, there is an urgent need to identify effective preventive therapies and treatments. Bisphosphonates may have a role in preventing osteopenia and, potentially, bone metastases among men with prostate carcinoma. Cancer 2000;88:2989–94. © 2000 American Cancer Society.
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A device for rectilinear and transverse-section scanning of the brain using 99m Tc pertechnetate is presented. The scanner has four detectors to view four different aspects of the brain simultaneously. A self-contained computer controls display and all automatic operations with no processing delay. This system permits more thorough studies with multiple rectilinear and transverse section views without moving the patient, precise orientation of views to each other and to the patient's position, minimal technician operations to assure simplicity and reliability, maximum physician operation to assure a complete examination, efficient transfer of information, and economy of design to encourage wide application.
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To evaluate the accuracy of ultrasound and parathyroid scintigraphy using single photon-emission computed tomography/computed tomography (SPECT/CT) for the preoperative localization of solitary parathyroid adenomas in patients with primary hyperparathyroidism who would be suitable for minimally invasive parathyroid surgery. Retrospective study of 63 consecutive patients with biochemical evidence of primary hyperparathyroidism referred for preoperative localization of parathyroid adenoma that proceeded to surgery in the same institution. All patients underwent high-resolution ultrasound and Technetium-99m sestamibi scintigraphy with planar and SPECT/CT imaging. The accuracy of preoperative imaging was compared to surgical and histological findings as the reference standard. Fifty-nine patients had solitary parathyroid adenomas, three patients had multiglandular hyperplasia, and one patient had multiple parathyroid adenomas confirmed at surgery and histology. Thirty-five solitary parathyroid adenomas were identified preoperatively with ultrasound (64%) and 53 with SPECT-CT (90%). Concordant ultrasound and SPECT/CT findings were found in 35 cases (59%). An additional three adenomas were found with ultrasound alone and 18 adenomas with SPECT/CT alone. Fifty-one of the 56 adenomas localized using combined ultrasound and SPECT/CT were found at the expected sites during surgery. Combined ultrasound and SPECT/CT has an overall sensitivity of 95% and accuracy of 91% for the preoperative localization of solitary parathyroid adenomas. The combination of ultrasound and SPECT/CT has incremental value in accurately localizing solitary parathyroid adenomas over either technique alone, and allows selection of patients with primary hyperparathyroidism who would be suitable for minimally invasive surgery.
Article
The high mortality and financial burden associated with prostate cancer can be partly attributed to a lack of sensitive screening methods for detection and staging of the disease. Guided by in silico docking studies using the crystal structure of PSMA, we designed and synthesized a series of PSMA-targeted (99m)Tc-chelate complexes for imaging PSMA-expressing human prostate cancer cells (LNCaP cell line). Of the six targeted radioimaging agents synthesized, three were found to bind LNCaP cells with low nanomolar affinity. Moreover, the same three PSMA-targeted imaging agents were shown to localize primarily to LNCaP tumor xenografts in nu/nu mice, with an average of 9.8 +/- 2.4% injected dose/g tissue accumulating in the tumor and only 0.11% injected dose/g tissue retained in the muscle at 4 h postinjection. Collectively, these high affinity, PSMA-specific radioimaging agents demonstrate significant potential for use in localizing prostate cancer masses, monitoring response to therapy, detecting prostate cancer recurrence following surgery, and selecting patients for subsequent PSMA-targeted chemotherapy.
Article
Medullary thyroid carcinoma (MTC) is a relatively rare neuroendocrine tumour originating from the parafollicular C cells and releases calcitonin (hCt), carcinoembryonic antigen (CEA) and occasionally other substances. In 20-30% of cases MTC presents a germline mutation of the RET proto-oncogene and occurs in 3 different hereditary forms: familial MTC, multiple endocrine neoplasia (MEN) 2A and MEN 2B syndrome. Prognosis of MTC is largely related to tumour extension at disease onset. Surgery remains the most effective therapy for potential cure. Overall survival is strictly linked to the occurrence of relapse. After surgery, serum hCt remains the most sensitive test for occult disease. Diagnostic imaging work-up includes ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, as the more frequent sites of recurrence or metastases are cervical and mediastinal lymph nodes, lungs, liver and bone. Nuclear medicine procedures include (111)In-labelled somatostatin analogs, radioiodinated metaiodobenzylguanidine (MIBG), and several PET radiopharmaceuticals. Experience with radionuclide therapy in MTC is restricted to few patients treated with (131)I-MIBG or (90)Y-DOTATOC. Since 1987, 1 027 diagnostic MIBG scans were performed in the Department Department of Diagnostic Imaging and Therapy of the Istituto Nazionale Tumori IRCCS Foundation (Milan, Italy), 85 of which for MTC, with a sensitivity of 38.7% in patients with evidence of disease and 30.7 % if all patients were considered. Since 1994, 13 MTC patients were treated with MIBG with 4 partial responses and 4 stable diseases. Patients with liver or bone involvement responded to therapy and showed long-term partial remission of disease, others showed stability of disease, which was apparently unrelated to therapy. Improvement of efficacy can be achieved through dosimetric calculation of administered activity.
Article
Technetium-99m methylene diphosphonate ([99mTc]MDP) is the most widely used bone-scanning agent today. In order to determine the precise bone locus of 99mTc corresponding to the delayed bone scan image, and to test the potential clinical use of this agent in enhancing the information obtained by bone scan, we employed [99mTc]MDP in this microautoradiographic study of normal bone and bone reparative tissue. Four white rabbits underwent operations in which two 1.5-mm drill holes were created in the subtrochanteric regions of both of their femora. An additional four white rabbits underwent sham operations of their femora, in which neither drilling nor periosteal injury occurred. Two rabbits were controls and did not undergo operation. After 7 days, the first two groups of rabbits were injected with [99mTc]MDP and bone scanned 2 h later. After the scans were completed, all three groups of animals were killed and their femora histologically processed for microautoradiography and routine histopathology. In the two groups that were injected with [99mTc]MDP, all bones showed the isotope to be clearly localized along mineralization fronts. The isotope was occasionally found in the substance of the osteoid, but was absent from the cytoplasm and nuclei of osteoblasts and osteocytes. Osteocytic lacunae showed the presence of isotope at their borders, but no identifiable pattern of isotope uptake was noted. Neither osteoclasts nor Howships lacunae showed isotope uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The authors describe the construction and operation of the Aberdeen Section Scanner (ASS) with a few clinical examples. The scanner is a dual headed device which can perform conventional rectilinear scans and the more recently developed section or tomographic scans. A punched paper-tape output from both heads is incorporated in the system so that count and position information may be fed into a PDP 81 computer enabling subsequent image processing and display. The same computer and display unit are optionally “on-line” to a Nuclear Enterprises gamma camera. The link to the ASS means that the advantages of computerized image processing are available for scans carried out with the new rectilinear scanner. Various design features are discussed together with the storage and display facilities. The routine operation of the scanner and the initial clinical results are also described.
Article
In 1952 Mayneord (1) proposed the usefulness of a transmission counter for plotting outlines of organs. Later, he produced images of lead letters by recording the transmitted beam from a Tm170 (84 keV) source which was maintained in direct alignment with the aperture of a scintillation detector during scanning (2, 3). In 1963, Cameron and Sorenson reported use of Am241 (60 keV) and I125 (30 keV) sources to determine bone mineral content by measuring the change in intensity of a transmitted photon beam moved across a bone (4). No clinical application of transmission scanning for forming images of body structures was reported by these authors. We have explored transmission scanning as a means of improving the orientation of the radionuclide emission scan (5). Accurate evaluation of a radionuclide distribution in the body requires that the spatial relationships of emission scan data be oriented to the anatomy of the patient. Usually, data on the scan record are keyed to anatomy either by using reference mark...
Article
Metastases are the major cause of treatment failure in cancer patients. Sixty percent of patients with newly diagnosed solid tumors (excluding skin cancers other than melanoma) have clinically evident or microscopic metastases when the primary tumor is diagnosed [1]. Dissemination of malignant cells throughout the body and their survival to form secondary growths constitute a complicated process dependent on both host and tumor properties. This review outlines the mechanisms involved in the metastatic process, the pathways of tumor spread throughout the body, and the common routes used by various tumors.
Article
Bisphosphonates are a unique class of drugs. As a family, they are characterized pharmacologically by their ability to inhibit bone resorption, whereas, pharmacokinetically, they are classified by their similarity in absorption, distribution, and elimination. Although all bisphosphonates have similar physicochemical properties, their antiresorbing activities differ substantially. Activity is dramatically increased when the amino group is contained in the aliphatic carbon chain. For example, alendronate, an aminobisphosphonate, is approximately 700-fold more potent than etidronate, both in vitro and in vivo. In general, bisphosphonates are poorly absorbed from the gastrointestinal tract as a result of their poor lipophilicity. In vitro and in vivo studies have shown that bisphosphonates are absorbed from the gastrointestinal tract via paracellular transport. Systemically available bisphosphonates disappear very rapidly from plasma, and are partly taken up by the bone and partly excreted by the kidney. The relative contribution of these two processes to overall plasma elimination differs significantly among bisphosphonates. To date, all bisphosphonates studied show no evidence of metabolism. Renal excretion is the only route of elimination. Studies with alendronate in rats indicate that the drug is actively secreted by an uncharacterized renal transport system, and not by the anionic or cationic renal transport systems. Bisphosphonates bind preferentially to bones which have high turnover rates, and their distribution in bone is not homogeneous. After bone uptake, the bisphosphonates are liberated again only when the bone in which they are deposited is resorbed. Thus, the half-life of bisphosphonates in bone is very long, ranging among different species from 1 to 10 years, depending largely on the rate of bone turnover.
Article
Objective: SPECT has become a routine procedure in most nuclear medicine departments. SPECT provides significant technical challenges for the nuclear medicine technologist, as compared with planar imaging, in the areas of SPECT acquisition, image reconstruction, and data processing. Many new advances in SPECT methodology are becoming available, such as iterative reconstruction, multimodality fusion, and advanced gated cardiac SPECT. SPECT imaging is demanding and requires careful attention to proper acquisition protocols, whether circular or noncircular orbits, and postprocessing is becoming more complex with the addition of iterative reconstruction and attenuation correction algorithms, among others. Understanding the principles of SPECT is essential not only to produce the highest quality scans but also to identify image artifacts. After reading this article, the nuclear medicine technologist should be able to: (a) describe the historical development and benefits of SPECT imaging; (b) state the impact of image matrix size, number of projections, and arc of rotation on final SPECT image quality; (c) discuss the trade-offs between image noise content and spatial and contrast resolution in SPECT reconstruction; (d) discuss SPECT filters and their impact on image quality; (e) explain the differences between filtered backprojection and iterative reconstruction; and (f) describe the impact of attenuation and scatter in SPECT imaging and the advantages and pitfalls of attenuation correction methods.
Article
Images of the inside of the human body can be obtained noninvasively using tomographic acquisition and processing techniques. In particular, these techniques are commonly used to obtain images of a gamma-emitter distribution after its administration in the human body. The reconstructed images are obtained given a set of their projections, acquired using rotating gamma cameras. A general overview of analytic and iterative methods of reconstruction in SPECT is presented with a special focus on filter backprojection (FBP), conjugate gradient, maximum likelihood expectation maximization, and maximum a posteriori expectation maximization algorithms. The FBP algorithm is faster than iterative algorithms, with the latter providing a framework for accurately modeling the emission and detection processes.
Article
Bone is the most common site to which breast cancer metastasizes. Imaging-by skeletal scintigraphy, plain radiography, computed tomography, or magnetic resonance imaging-is an essential part, and positron emission tomography or single-photon emission computed tomography have a potential of evaluating bone metastases, but no consensus exists as to the best modality for diagnosing the lesion and for assessing its response to treatment. Imaging bone metastases is problematic because the lesions can be osteolytic, osteoblastic, or mixed, and imaging modalities are based on either direct anatomic visualization of the bone or tumor or indirect measurements of bone or tumor metabolism. Although bone metastases can be treated, their response to treatment is considered "unmeasurable" according to existing response criteria. Therefore, the process by which oncologists and radiologists diagnose and monitor the response of bone metastases needs revision, and the current inability to assess the response of bone metastases excludes patients with breast cancer and bone disease from participating in clinical trials of new treatments for breast cancer. In this review of the MEDLINE literature, we discuss the pros and cons of each modality for diagnosing bone metastases and for assessing their response to treatment and we present a practical approach for diagnosis and assessment of bone metastasis.
Article
Prostate-specific membrane antigen (PSMA) is a metallopeptidase expressed predominantly in prostate cancer (PCa) cells. PSMA is considered a biomarker for PCa and is under intense investigation for use as an imaging and therapeutic target. Although the clinical utility of PSMA in the detection and treatment of PCa is evident and is being pursued, very little is known about its basic biological function in PCa cells. The purpose of this review is to highlight the possibility that PSMA might be a multifunctional protein. We suggest that PSMA may function as a receptor internalizing a putative ligand, an enzyme playing a role in nutrient uptake, and a peptidase involved in signal transduction in prostate epithelial cells. Insights into the possible functions of PSMA should improve the diagnostic and therapeutic values of this clinically important molecule.
Article
The purpose of this study was to investigate the added value of co-registered fusion imaging using a hybrid system in patients with lymphoma. Twenty-four lymphoma patients underwent (67)Ga-SPECT/CT using a hybrid tomograph consisting of a dual-head, variable-angle gamma camera and a low-dose X-ray tube. Results were compared with those of SPECT alone. Forty-five lesions were identified by SPECT alone, while 49 were detected by SPECT/CT. Forty out of the 45 lesions observed on SPECT were confirmed as lymphoma, but five were due to other causes (thoracic aorta blood pool activity, sialoadenitis in the submandibular gland, bowel activity, rib fracture and bone marrow activation due to radiotherapy). SPECT/CT identified nine more neoplastic lesions compared with SPECT alone: four areas of radiopharmaceutical accumulation were observed in para-aortic lymph nodes, three in the spleen, one in the liver and one in para-iliac lymph nodes. In five cases, SPECT/CT provided additional anatomical information over SPECT alone. In four patients, four large areas of (67)Ga uptake (one mediastinal, two supraclavicular and one para-aortic) were better characterised; in one subject uptake was localised in the seventh thoracic vertebra only by SPECT/CT. Hybrid imaging provided additional data in 13 patients (54.2%), thus inducing oncologists to reconsider the therapeutic approach in eight subjects (33.2%): unnecessary treatment was avoided in four (16.6%) while therapy was altered in another four (16.6%). SPECT/CT hybrid system is able to provide information not obtained by SPECT alone. It allows the anatomical localisation of lymphoma and physiological radiopharmaceutical uptake, facilitates the diagnosis of tumours located in the abdomen (subdiaphragmatic lesions) and provides information that may cause a change in therapeutic strategy.
Article
Detection of bone involvement is essential for optimal therapy of oncologic patients. The purpose of imaging is to identify early bone involvement, to determine the full extent of the skeletal disease, to assess the presence of accompanying complications-such as fractures and cord compression-and to monitor response to therapy. Detection of bone involvement by various imaging modalities is based on either direct visualization of tumor infiltration or detection of the reaction of bone to the malignant process. MRI can identify early involvement of bone marrow. CT, which depends mainly on bone destruction, provides detailed bone morphology. In nuclear medicine, uptake of (18)F-FDG is directly into tumor cells, thus allowing for early detection and monitoring the response to therapy of tumor sites in the marrow, bone, and soft tissue, whereas increased uptake of (18)F-fluoride and (99m)Tc-methylene diphosphonate reflects the osteoblastic reaction of bone to the presence of tumor cells. The hybrid techniques SPECT/CT and PET/CT, recently introduced into clinical practice, provide a better anatomic localization of scintigraphic findings and may improve the diagnostic accuracy of SPECT and PET in detecting malignant bone involvement. The current review discusses the basis for the detection of malignant bone involvement by various morphologic and scintigraphic imaging modalities and the advantages and the limitations of each. Special emphasize is placed on the newer integrated technique of PET/CT. The role of imaging in identifying bone involvement in different malignant diseases is also discussed.
Article
67Ga scintigraphy is an established method for the staging and follow-up of patients diagnosed of lymphomas. The aim of this study is to evaluate advantages of 67Ga SPECT-CT study over planar, SPECT and high resolution CT studies in lymphoma disease. One hundred and one 67Ga studies corresponding to 74 patients (46 men) were obtained, mean age 44 years. Thirty-eight patients (51 %) were diagnosed of Hodgkin's lymphoma and 36 were non-Hodgkin's lymphoma. All patients were evaluated with 67Ga and high-resolution CT studies. 67Ga studies were performed in a hybrid system, obtaining planar, SPECT and fused SPECT-CT imaging. Findings obtained from 67Ga studies were correlated with findings obtained from CT studies, both much in number of tumoral lesions and in their localization. Planar, SPECT, SPECT-CT and CT studies detected 123, 146, 155 and 132 lesions respectively. SPECT-CT and CT were concordant in 52 studies, while there was no concordance between SPECT-CT and CT in the remaining 49 studies, SPECT-CT detecting more lesions than CT in 28 of them. These findings changed the disease stage 18 times (18 % of whole studies). These results show better efficiency of 67Ga SPECT-CT compared to the other acquisition methods of 67Ga study and to CT for detection of tumoral lymphomatous lesions. 67Ga SPECT-CT study improves the diagnostic yield of the study with 67Ga in patients with lymphoma, providing better anatomical localization of tumoral lesions and detection of extraganglionar disease.
Article
To evaluate the incremental benefit in routine clinical practice of computed tomography (CT) scans acquired for anatomical localization on an integrated SPECT/CT which incorporates a spiral CT scanner, in comparison with conventional planar and SPECT scanning. The first 50 studies acquired on the integrated system were evaluated by two experienced nuclear medicine physicians who were aware of the patient's clinical history. These included bone scans, gallium scans, octreotide scans, sestamibi parathyroid scans and MIBG scans. For each patient study, abnormalities were assessed on planar and SPECT images for location and provisional diagnosis and a quantitative scale was used to assess reporter confidence. The fused SPECT/CT images were then reviewed and the location and provisional diagnosis noted and reporter confidence was assessed using the same quantitative scale. There were 129 abnormalities detected in 50 patient studies. For localization of abnormalities, the inclusion of the CT resulted in a minor change in 16% of cases and a significant change in 11% over planar/SPECT imaging alone. The confidence of localization was improved moderately in 19% and improved significantly in 6%. For diagnosis, SPECT/CT resulted in a minor change in 10% and a significant change in 9% over planar/SPECT imaging. The confidence of diagnosis was improved moderately in 10% and improved significantly in a further 10% of cases. For the final scan interpretation, there would have been no change in 44% patients, a minor change in 30% and a significant change in 26% with the use of SPECT/CT. Use of integrated SPECT/CT with a high spatial resolution, spiral CT used for anatomical localization improves accuracy and reporter confidence in clinical practice. As a result, final reports were different in 56% of the cases, including being significantly different in 26% patients compared to reporting with planar/SPECT alone.
Article
Single-photon emission computed tomography/computed tomography (SPECT/CT) has emerged during the past decade as a means of correlating anatomical information from CT with functional information from SPECT. The integration of SPECT and CT in a single imaging device facilitates anatomical localization of the radiopharmaceutical to differentiate physiological uptake from that associated with disease and patient-specific attenuation correction to improve the visual quality and quantitative accuracy of the SPECT image. The first clinically available SPECT/CT systems performed emission-transmission imaging using a dual-headed SPECT camera and a low-power x-ray CT subsystem. Newer SPECT/CT systems are available with high-power CT subsystems suitable for detailed anatomical diagnosis, including CT coronary angiography and coronary calcification that can be correlated with myocardial perfusion measurements. The high-performance CT capabilities also offer the potential to improve compensation of partial volume errors for more accurate quantitation of radionuclide measurement of myocardial blood flow and other physiological processes and for radiation dosimetry for radionuclide therapy. In addition, new SPECT technologies are being developed that significantly improve the detection efficiency and spatial resolution for radionuclide imaging of small organs including the heart, brain, and breast, and therefore may provide new capabilities for SPECT/CT imaging in these important clinical applications.
Detection of prostate cancer and predicting progression : Current and future diagnostic
  • Tricoli
The use of 99mTc as a clinical tracer element
  • Herbert