(99m)Tc-DPD-SPECT/CT predicts the outcome of imaging-guided diagnostic anaesthetic injections: A prospective cohort study

We hypothesized that bone SPECT combined with multiplanar reconstructed CT can identify and target the pain-inducing focus in the foot and can be used to successfully guide anaesthetic infiltrations. Therefore we prospectively investigated feasibility and predictive value of bone SPECT/CT for image guided diagnostic infiltrations in patients with chronic foot pain.

Advantages of preoperative hybrid SPECT/CT in detection of sentinel lymph nodes in cutaneous head and neck malignancies

There is some controversy around the value of sentinel lymph node excision (SLNE). Especially SLNE of cutaneous head and neck malignancies has been debated intensively, in part because of the complexity of the lymphatic drainage in this region associated with potential high morbidity. In order to improve preoperative three-dimensional mapping of sentinel lymph nodes (SLN), in the head and neck region, by means of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) is gaining significance. Our study seeks to identify the potential medical and economic advantages of preoperative SPECT/CT in direct comparison to standard SLNE without SPECT/CT in patients with cutaneous head and neck malignancies.

[SPECT/CT diagnostics for skeletal infections]

CLINICAL/METHODICAL ISSUE: Skeletal infections are often a diagnostic and clinical challenge. STANDARD RADIOLOGICAL METHODS: Nuclear imaging modalities used in the diagnostic workup of acute and chronic skeletal infections include three-phase bone scintigraphy and scintigraphy with labelled leucocytes. METHODICAL INNOVATIONS: The introduction of hybrid technologies, such as single photon emission computed tomography/computed tomography (SPECT/CT) has dramatically changed nuclear medical imaging of infections. PERFORMANCE: In general SPECT/CT leads to a considerably more accurate diagnosis than planar or SPECT imaging. ACHIEVEMENTS: Given the integrated acquisition of metabolic, functional and morphological information, SPECT/CT has increased in particular the specificity of three-phase skeletal scanning and scintigraphy with labeled leucocytes.

Association between sentinel lymph node excision with or without preoperative SPECT/CT and metastatic node detection and disease-free survival in melanoma

Malignant melanoma has become an increasing interdisciplinary public health challenge worldwide. Sentinel lymph node excision (SLNE) is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes.

Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing

UNLABELLED The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. PATIENTS, MATERIAL AND METHODS 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. RESULTS Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. CONCLUSIONS SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients with pulmonary emphysema?

PURPOSE To evaluate the utility of attenuation correction (AC) of V/P SPECT images for patients with pulmonary emphysema. MATERIALS AND METHODS Twenty-one patients (mean age 67.6 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point likert scale. Semiquantitative comparison assessed absolute counts per lung (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis; percentage counts (PC = (aCpLo/aCpLu) × 100) were calculated. Correlation between AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation coefficient; differences were tested for significance with the Wilcoxon rank sum test. RESULTS Visual analysis revealed high conformity for AC and non-AC V/P SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an excellent correlation and showed no significant differences in perfusion (ρ = 0.986) or ventilation (ρ = 0.979, p = 0.809) SPECT/CT images. CONCLUSION AC of V/P SPECT images for lung lobe-based function imaging in patients with pulmonary emphysema do not improve visual or semiquantitative image analysis.

Cardiac image fusion from stand-alone SPECT and CT: clinical experience

Myocardial perfusion imaging with SPECT (SPECT-MPI) and 64-slice CT angiography (CTA) are both established techniques for the noninvasive evaluation of coronary artery disease (CAD). Three-dimensional (3D) SPECT/CT image fusion may offer an incremental diagnostic value by integrating both sets of information. We report our first clinical experiences with fused 3D SPECT/CT in CAD patients. METHODS: Thirty-eight consecutive patients with at least 1 perfusion defect on SPECT-MPI (1-d adenosine stress/rest SPECT with (99m)Tc-tetrofosmin) and 64-slice CTA were included. 3D volume-rendered fused SPECT/CT images were generated and compared with the findings from the side-by-side analysis with regard to coronary lesion interpretation by assigning the perfusion defects to their corresponding coronary lesion. RESULTS: The fused SPECT/CT images added information on pathophysiologic lesion severity in 27 coronary stenoses (22%) of 12 patients (29%) (P<0.001). Among 40 equivocal lesions on side-by-side analysis, the fused interpretation confirmed hemodynamic significance in 14 lesions and excluded functional relevance in 10 lesions. In 3 lesions, assignment of perfusion defect and coronary lesion appeared to be reliable on side-by-side analysis but proved to be inaccurate on fused interpretation. Added diagnostic information by SPECT/CT was more commonly found in patients with stenoses of small vessels (P=0.004) and involvement of diagonal branches (P=0.01). CONCLUSION: In addition to being intuitively convincing, 3D SPECT/CT fusion images in CAD may provide added diagnostic information on the functional relevance of coronary artery lesions.

Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT within patients with gastroenteropancreatic neuroendocrine tumors

Somatostatin receptor PET tracers such as [68Ga-DOTA,1-Nal3]-octreotide (68Ga-DOTANOC) and [68Ga-DOTA,Tyr3]-octreotate (68Ga-DOTATATE) have shown promising results in patients with neuroendocrine tumors, with a higher lesion detection rate than is achieved with 18F-fluorodihydroxyphenyl-l-alanine PET, somatostatin receptor SPECT, CT, or MR imaging. 68Ga-DOTANOC has high affinity for somatostatin receptor subtypes 2, 3, and 5 (sst2,3,5). It has a wider receptor binding profile than 68Ga-DOTATATE, which is sst2-selective. The wider receptor binding profile might be advantageous for imaging because neuroendocrine tumors express different subtypes of somatostatin receptors. The goal of this study was to prospectively compare 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT in the same patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to evaluate the clinical impact of 68Ga-DOTANOC PET/CT. Methods: Eighteen patients with biopsy-proven GEP-NETs were evaluated with 68Ga-DOTANOC and 68Ga-DOTATATE using a randomized crossover design. Labeling of DOTANOC and DOTATATE with 68Ga was standardized using a fully automated synthesis device. PET/CT findings were compared with 3-phase CT scans and in some patients with MR imaging, 18F-FDG PET/CT, and histology. Uptake in organs and tumor lesions was quantified and compared by calculation of maximum standardized uptake values (SUVmax) using volume computer-assisted reading. Results: Histology revealed low-grade GEP-NETs (G1) in 4 patients, intermediate grade (G2) in 7, and high grade (G3) in 7. 68Ga-DOTANOC and 68Ga-DOTATATE were false-negative in only 1 of 18 patients. In total, 248 lesions were confirmed by cross-sectional and PET imaging. The lesion-based sensitivity of 68Ga-DOTANOC PET was 93.5%, compared with 85.5% for 68Ga-DOTATATE PET (P = 0.005). The better performance of 68Ga-DOTANOC PET is attributed mainly to the significantly higher detection rate of liver metastases rather than tumor differentiation grade. Multivariate analysis revealed significantly higher SUVmax in G1 tumors than in G3 tumors (P = 0.009). This finding was less pronounced with 68Ga-DOTANOC (P > 0.001). Altogether, 68Ga-DOTANOC changed treatment in 3 of 18 patients (17%). Conclusion: The sst2,3,5-specific radiotracer 68Ga-DOTANOC detected significantly more lesions than the sst2-specific radiotracer 68Ga-DOTATATE in our patients with GEP-NETs. The clinical relevance of this finding has to be proven in larger studies.

Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice

We assessed the suitability of the radiolanthanide 155 Tb (t1/2 = 5.32 days, Eγ = 87 keV (32%), 105 keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. Methods 155Tb was produced at ISOLDE (CERN, Geneva, Switzerland) by high-energy (~ 1.4 GeV) proton irradiation of a tantalum target followed by ionization and on-line mass separation. 155 Tb was separated from isobar and pseudo-isobar impurities by cation exchange chromatography. Four tumor targeting molecules – a somatostatin analog (DOTATATE), a minigastrin analog (MD), a folate derivative (cm09) and an anti-L1-CAM antibody (chCE7) – were radiolabeled with 155 Tb. Imaging studies were performed in nude mice bearing AR42J, cholecystokinin-2 receptor expressing A431, KB, IGROV-1 and SKOV-3ip tumor xenografts using a dedicated small-animal SPECT/CT scanner. Results The total yield of the two-step separation process of 155 Tb was 86%. 155 Tb was obtained in a physiological l-lactate solution suitable for direct labeling processes. The 155 Tb-labeled tumor targeted biomolecules were obtained at a reasonable specific activity and high purity (> 95%). 155 Tb gave high quality, high resolution tomographic images. SPECT/CT experiments allowed excellent visualization of AR42J and CCK-2 receptor-expressing A431 tumors xenografts in mice after injection of 155 Tb-DOTATATE and 155 Tb-MD, respectively. The relatively long physical half-life of 155 Tb matched in particular the biological half-lives of 155 Tb-cm09 and 155 Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. Conclusions The radiolanthanide 155 Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β--emitting radiolanthanides 177Lu, 161 Tb, 166Ho, and the pseudo-radiolanthanide 90Y.

Localization of Hidden Insulinomas with 68Ga-DOTA-Exendin-4 PET/CT: A Pilot Study.

UNLABELLED (111)In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle(14),Lys(40)(Ahx-DOTA-(68)Ga)NH2]exendin-4 ((68)Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. METHODS (68)Ga-DOTA-exendin-4 PET/CT and (111)In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. RESULTS In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive (68)Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. (68)Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas (111)In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. CONCLUSION These preliminary data suggest that the use of (68)Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.

[Lys40(Ahx-DTPA-111In)NH2]exendin-4, a very promising ligand for glucagon-like peptide-1 (GLP-1) receptor targeting

High levels of glucagon-like peptide-1 (GLP-1) receptor expression in human insulinomas and gastrinomas provide an attractive target for imaging, therapy, and intraoperative tumor localization, using receptor-avid radioligands. The goal of this study was to establish a tumor model for GLP-1 receptor targeting and to use a newly designed exendin-4-DTPA (DTPA is diethylenetriaminepentaacetic acid) conjugate for GLP-1 receptor targeting. METHODS: Exendin-4 was modified C-terminally with Lys(40)-NH(2), whereby the lysine side chain was conjugated with Ahx-DTPA (Ahx is aminohexanoic acid). The GLP-1 receptor affinity (50% inhibitory concentration [IC(50)] value) of [Lys(40)(Ahx-DTPA)NH(2)]exendin-4 as well as the GLP-1 receptor density in tumors and different organs of Rip1Tag2 mice were determined. Rip1Tag2 mice are transgenic mice that develop insulinomas in a well-defined multistage tumorigenesis pathway. This animal model was used for biodistribution studies, pinhole SPECT/MRI, and SPECT/CT. Peptide stability, internalization, and efflux studies were performed in cultured beta-tumor cells established from tumors of Rip1Tag2 mice. RESULTS: The GLP-1 receptor affinity of [Lys(40)(Ahx-DTPA)NH(2)]exendin-4 was found to be 2.1 +/- 1.1 nmol/L (mean +/- SEM). Because the GLP-1 receptor density in tumors of Rip1Tag2 mice was very high, a remarkably high tumor uptake of 287 +/- 62 %IA/g (% injected activity per gram tissue) was found 4 h after injection. This resulted in excellent tumor visualization by pinhole SPECT/MRI and SPECT/CT. In accordance with in vitro data, [Lys(40)(Ahx-DTPA-(111)In)NH(2)]exendin-4 uptake in Rip1Tag2 mice was also found in nonneoplastic tissues such as pancreas and lung. However, lung and pancreas uptake was distinctly lower compared with that of tumors, resulting in a tumor-to-pancreas ratio of 13.6 and in a tumor-to-lung ratio of 4.4 at 4 h after injection. Furthermore, in vitro studies in cultured beta-tumor cells demonstrated a specific internalization of [Lys(40)(Ahx-DTPA-(111)In)NH(2)]exendin-4, whereas peptide stability studies indicated a high metabolic stability of the radiopeptide in beta-tumor cells and human blood serum. CONCLUSION: The high density of GLP-1 receptors in insulinomas as well as the high specific uptake of [Lys(40)(Ahx-DTPA-(111)In)NH(2)]exendin-4 in the tumor of Rip1Tag2 mice indicate that targeting of GLP-1 receptors in insulinomas may become a useful imaging method to localize insulinomas in patients, either preoperatively or intraoperatively. In addition, Rip1Tag2 transgenic mice represent a suitable animal tumor model for GLP-1 receptor targeting.

Peptide-based probes for cancer imaging

Receptors for regulatory peptides are overexpressed in a variety of human cancers. They represent the molecular basis for in vivo imaging with radiolabeled peptide probes. Somatostatin-derived tracers, designed to image the sst2-overexpressing neuroendocrine tumors, have enjoyed almost 2 decades of successful development and extensive clinical applications. More recent developments include second- and third-generation somatostatin analogs, with a broader receptor subtype profile or with antagonistic properties. Emerging tracers for other peptide receptors, including cholecystokinin/gastrin and GLP-1 analogs for neuroendocrine tumors, bombesin and neuropeptide-Y analogs for prostate or breast cancers, or Arg-Gly-Asp peptides for neoangiogenesis labeling, are also in current development. Application fields include both SPECT/CT and PET/CT.