Edmund E. Kim

A review on the clinical uses of SPECT/CT

In the era when positron emission tomography (PET) seems to constitute the most advanced application of nuclear medicine imaging, still the conventional procedure of single photon emission computed tomography (SPECT) is far from being obsolete, especially if combined with computed tomography (CT). In fact, this dual modality imaging technique (SPECT/CT) lends itself to a wide variety of useful diagnostic applications whose clinical impact is in most instances already well established, while the evidence is growing for newer applications. The increasing availability of new hybrid SPECT/CT devices with advanced technology offers the opportunity to shorten acquisition time and to provide accurate attenuation correction and fusion imaging. In this review we analyse and discuss the capabilities of SPECT/CT for improving sensitivity and specificity in the imaging of both oncological and non-oncological diseases. The main advantages of SPECT/CT are represented by better attenuation correction, increased specificity, and accurate depiction of the localization of disease and of possible involvement of adjacent tissues. Endocrine and neuroendocrine tumours are accurately localized and characterized by SPECT/CT, as also are solitary pulmonary nodules and lung cancers, brain tumours, lymphoma, prostate cancer, malignant and benign bone lesions, and infection. 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. Finally, the applications of SPECT/CT to other clinical disorders or malignant tumours is currently under extensive investigation, with encouraging results in terms of diagnostic accuracy.

Comparative study of FDG PET/CT and conventional imaging in the staging of rhabdomyosarcoma

ObjectiveThe current study was conducted to compare the diagnostic accuracy between 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT), and conventional imaging (CI) for the staging and re-staging of patients with rhabdomyosarcomas.MethodsThirty-five patients who underwent FDG PET/CT prior to treatment were evaluated retrospectively. CI methods consisted of 99mTc-hydroxymethylene diphosphonate bone scintigraphy, chest radiograph, whole body CT, and magnetic resonance imaging of the primary site. The images were reviewed and two boardcertified radiologists reached a diagnostic consensus. Tumor stage was confirmed by histological examination and/or follow-up examinations.ResultsInterpretation on the basis of FDG PET/CT, and CI, diagnostic accuracies of the T and N stages were similar. Using FDG PET/CT, the M stage was correctly assigned in 31 patients (89%), whereas the accuracy of CI in M stage was 63%. TNM stage was correctly assessed with FDG PET/CT in 30 of 35 patients (86%) and with CI in 19 of 35 patients (54%). The overall TNM staging and M staging accuracies of FDG PET/CT were significantly higher than that of CI (P < 0.01).ConclusionsFDG PET/CT is more accurate than CI regarding clinical staging and re-staging of patients with rhabdomyosarcomas.

Noninvasive Assessment of Tumor Hypoxia with 99mTc Labeled Metronidazole

AbstractPurpose. The assessment of tumor hypoxia by imaging modality prior to radiation therapy would provide a rational means of selecting patients for treatment with radiosensitizers or bioreductive drugs. This study aimed to develop a 99mTc-labeled metronidazole (MN) using ethylene-dicysteine (EC) as a chelator and evaluate its potential use to image tumor hypoxia. Methods. EC was conjugated to amino analogue of MN using Sulfo-N-hydroxysuccinimide and l-ethyl-3-(3-dimethylaminopropyl) carbodiimide-HCl as coupling agents, the yield was 55%. Tissue distribution of 99mTc-EC-MN was determined in breast tumor-bearing rats at 0.5, 2, and 4 hrs. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using 99mTc-EC (control), [l8F]fluoromisonidazole (FMISO) and [131I] iodomisonidazole (IMISO). Results. In vivo biodistribution of 99mTc-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to-muscle ratios as a function of time. Conversely, tumor-to-blood values showed time-dependent decrease with 99mTc-EC in the same time period. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with 99mTc-EC-MN from 0.5 to 4 hrs. There was no significant difference of tumor-to-blood count ratios between 99mTc-EC-MN and [131I]IMISO at 2 and 4 hrs postinjection. From 0.5 to 4 hrs, both 99mTc-EC-MN and [131I]IMISO have higher tumor-to-muscle ratios compared to [18]FMISO. Conclusions. It is feasible to use 99mTc-EC-MN to image tumor hypoxia.

Is the lung scan alive and well? Facts and controversies in defining the role of lung scintigraphy for the diagnosis of pulmonary embolism in the era of MDCT

PurposeThe last decade has seen a changing pattern of utilization of multidetector CT (MDCT) versus lung perfusion scintigraphy in the investigation of pulmonary venous thromboembolism (VTE). In response to this the International Atomic Energy Agency (IAEA) determined that the subject required an overview.MethodThe IAEA has invited a group of five specialists in the relevant fields to review the current status and optimum role of scintigraphy, to explore some of the facts and controversies surrounding the use of both modalities and to make recommendations about the continued role of nuclear medicine for the investigation of pulmonary embolism. This paper identifies the relative merits of each technique, highlights benefits, focuses on complementary roles and seeks a nonadversarial symbiosis.ConclusionThe consultants reached a consensus that the continued use of scintigraphy for diagnosis of thromboembolic disease is recommended, particularly in scenarios where scintigraphy confers specific benefits and is complementary to MDCT.

Sentinel node mapping in vulvovaginal melanoma using SPECT/CT lymphoscintigraphy

We report 2 cases of vulvovaginal melanoma in which sentinel node mapping, performed using Tc-99m filtered sulfur colloid SPECT/CT lymphoscintigraphy, added important information to that provided by planar imaging and played a critical role in surgical planning and subsequent management. In the first case, lymphoscintigraphy planar imaging showed only foci of tracer uptake in the right groin and an equivocal focus in the left groin. SPECT/CT precisely localized these radioactive foci to the right and left inguinal sentinel nodes. The patient then underwent bilateral inguinal sentinel node sampling. In the second case, F-18 FDG PET/CT performed prior to lymphoscintigraphy demonstrated a moderately FDG-avid right inguinal lymph node that was indeterminate in nature. SPECT/CT revealed this lymph node to be a radioactive sentinel lymph node that was seen in the right groin on planar imaging. The patient then underwent right inguinal sentinel node sampling. Because pathologic study showed metastasis to the sentinel node, a planned pelvic exenteration was canceled, and the patient was referred for systemic treatment. Preoperative SPECT/CT lymphoscintigraphy is ideal for mapping the unpredicted lymphatic drainage pathways within the complex pelvic anatomy and this technique may also be used in the preoperative workup of other gynecologic malignancies.

Correlation of chromogranin A levels and somatostatin receptor scintigraphy findings in the evaluation of metastases in carcinoid tumors

ObjectiveChromogranin A (CgA) has been gaining acceptance as a helpful tumor marker in patients with neuroendocrine tumors, with respect to both diagnosis and prognosis. The objective of this study was to correlate serum CgA levels and somatostatin receptor scintigraphy (SRS) findings in the evaluation of metastases in carcinoid tumors.Materials and methodsA total of 125 patients(61 men and 64 women, aged from 23 to 84 years) with histologically diagnosed carcinoid tumor underwent serum CgA assay and SRS for detecting metastasis or disease recurrence. The quantitative determination of CgA was performed in serum using an enzyme immunoassay with a cut-off value fixed at 39 U/l. Scintigraphies were performed with 200–220 MBq of In-111-DTPA-Phel-octreotide including whole-body images as well as single-photon emission computed tomography and computed tomography scans of the chest and abdomen.ResultsThe primary tumors originated from the gastrointestinal tract in 115 of 125 patients (92.0%), the lung in 7 of 125 patients (5.6%), the kidney in 2 of 125 patients (1.6%), and the breast in 1 of 125 patients (0.8%). The primary tumors originated from the foregut, midgut, and hindgut in 13.6%, 71.2%, and 12.8%, respectively. Correlation of SRS with other imaging modalities and clinical follow-up findings revealed a sensitivity, a specificity, and an accuracy of 82.9%, 97.7%, and 88.0%, respectively, and for CgA 62.2%, 83.7%, and 69.6%, respectively. There was 1 false-positive and 14 falsenegative SRS results and 7 false-positive and 31 falsenegative CgA analyses. SRS demonstrated higher sensitivity, specificity, and accuracy than CgA for the evaluation of metastatic carcinoid tumors. The concordance between SRS and CgA results was 67.2%. Discrepancies, such as positive SRS with normal CgA levels, were noted in 26 (20.8%) cases, whereas negative SRS with high CgA levels was seen in 15 (12.0%) cases. Combining the results of CgA and SRS increased the sensitivity (92.7%) but decreased the specificity (81.4%) of tumor detection.ConclusionsIn our study, SRS proved to be more sensitive, more specific, and more accurate than CgA for metastatic evaluation of carcinoid tumors. Positive SRS correlated with elevation of serum CgA levels. Serum CgA might have some diagnostic utility in patients with negative SRS studies. Nevertheless, both SRS and CgA should be considered useful tools in the evaluation of metastases in carcinoid patients.

Diagnostic performance of PET/CT in differentiation of malignant and benign non-solid solitary pulmonary nodules

ObjectiveTo evaluate whether [F-18] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can distinguish benign from malignant solitary pulmonary nodules (SPNs) with non-solid components.Methods[F-18] FDG-PET/CT scans were performed on 53 consecutive patients (30 men, 23 women; mean age 65 years) who had SPNs with non-solid components identified by CT screening for lung cancer. All patients underwent surgical resection, and all lesions were pathologically proved. Visual score, maximal, and mean standardized uptake value (SUV), and maximal and mean lesion-to-normal tissue count density ratio (LNR) were calculated in all lesions. In addition, clinical characteristics, laboratory test results, and CT findings were assessed.ResultsBenign SPNs with non-solid components had a higher uptake on [F-18] FDG-PET/CT. Visual score, maximal and mean SUV, and maximal and mean LNR were significantly higher in the benign when compared with the malignant SPNs (P < 0.001). When the cutoff of 1.5 was assigned for maximal SUV, the diagnostic performance of [F-18] FDG-PET/CT in predicting benign SPN revealed 100.0% sensitivity, 96.4% specificity, and 100.0% accuracy.Conclusions[F-18] FDG-PET/CT is useful for the differential diagnosis of SPNs with non-solid components.

Synthesis of [18F]Fluoroalanine and [18F]Fluorotamoxifen for Imaging Breast Tumors

To develop ligands for imaging breast tumors, [18F]fluoro analogue of tamoxifen and [18F]fluoroalanine were radiosynthesized. In vivo biodistribution studies were performed in mammary tumor-bearing rats. In studies on the biodistribution of an [18F]fluoro analogue of tamoxifen, tumor uptake decreased when rats were pretreated with diethylstilbestrol (DES), suggesting that tracer uptake in tumors was receptor-mediated. An estrogen receptor assay indicated that tumors have a receptor density of 7.5 fmol/mg protein. Studies of the distribution of [18F]fluoroalanine in tissue showed that the tumor-to-tissue ratio increases as a function of time. Positron emission tomography (PET) images of tumor-bearing rats demonstrated that tumors can be visualized 1 h after rats are injected with an [18F]fluoro analogue of tamoxifen. PET imaging of pigs after injection of 10 mCi of [18F]fluoro analogue of tamoxifen showed uterine uptake that could be blocked by DES (50 mg). The findings suggest that both radiotracers are useful for imaging breast tumors.

Modern Approach to Surgical Intervention of the Thyroid and Parathyroid Glands

Operative intervention on the parathyroid and thyroid glands has become more minimally invasive and selective over the past decade. This requires high-quality preoperative imaging evaluation for better knowledge of the relevant anatomical considerations and potential localization. Minimally invasive parathyroidectomy has become the operation of choice for most patients presenting with sporadic primary hyperparathyroidism (when the suspected parathyroid tumor is localized preoperatively). Preoperative imaging helps guide the surgeon as to which patients with thyroid pathology require intervention and the extent of resection. The imaging modalities reviewed include ultrasonography, technetium-99m sestamibi imaging, and four-dimensional computed tomography. Imaging modalities are discussed within the categories of benign and neoplastic parathyroid and thyroid pathology.

Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor-bearing rats.

The aim of this study was to develop an 111In-labeled diethylenetriamine pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adriamycin with DTPA anhydride in the presence of carbonyldiimidazole. After dialysis (MW cut off was 500), the product was freeze-dried (yield 40-50%). An in vitro cell culture study was performed using cells from the 13,762 Fischer rat mammary tumor line. Drug concentrations tested were 0.1-100 microM. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time interval, 10 microCi/rat, i.v.) with 13,762 cells (10(5) cells/rat, s.c.). Planar imaging and autoradiograms were obtained at the same intervals. In vitro cell culture assays showed an IC50 of 0.1 +/- 0.01 microM for ADR and 7.2 +/- 0.29 microM for DTPA-ADR, respectively. In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5, 2, 24 and 48 h were 0.55 +/- 0.17, 0.94 +/- 0.17, 3.06 +/- 0.53 and 3.66 +/- 0.35, respectively, whereas those for [111In]DTPA (control) were 1.19 +/- 0.69, 0.84 +/- 0.07, 0.56 +/- 0.10 and 0.60 +/- 0.03, respectively. The tumor uptake value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and autoradiograms showed good visability of tumors. Biodistribution, autoradiography and radionuclide imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h. These results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in the diagnosis of breast cancer and may predict a therapeutic effect prior to treatment.