Thorsten D. Poeppel

68Ga-DOTATOC Versus 68Ga-DOTATATE PET/CT in Functional Imaging of Neuroendocrine Tumors

Radiolabeled somatostatin analogs represent valuable tools for both in vivo diagnosis and therapy of neuroendocrine tumors (NETs) because of the frequent tumoral overexpression of somatostatin receptors (sst). The 2 compounds most often used in functional imaging with PET are 68Ga-DOTATATE and 68Ga-DOTATOC. Both ligands share a quite similar sst binding profile. However, the in vitro affinity of 68Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately 10-fold higher than that of 68Ga-DOTATOC. This difference may affect their efficiency in the detection of NET lesions because it is the sst2 that is predominantly overexpressed in NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs (68Ga-DOTATATE and 68Ga-DOTATOC) in the same NET patients. Methods: Forty patients with metastatic NETs underwent 68Ga-DOTATOC and 68Ga-DOTATATE PET/CT as part of the work-up before prospective peptide receptor radionuclide therapy. The performance of both imaging methods was analyzed and compared for the detection of individual lesions per patient and for 8 defined body regions. A region was regarded positive if at least 1 lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUVmax) was compared for concordant lesions and renal parenchyma. Results: Seventy-eight regions were found positive with 68Ga-DOTATATE versus 79 regions with 68Ga-DOTATOC (not significant). Overall, however, significantly fewer lesions were detected with 68Ga-DOTATATE than with 68Ga-DOTATOC (254 vs. 262, P < 0.05). Mean 68Ga-DOTATATE SUVmax across all lesions was significantly lower than 68Ga-DOTATOC (16.0 ± 10.8 vs. 20.4 ± 14.7, P < 0.01). Mean SUVmax for renal parenchyma was not significantly different between 68Ga-DOTATATE and 68Ga-DOTATOC (12.7 ± 3.0 vs. 13.2 ± 3.3). Conclusion: 68Ga-DOTATOC and 68Ga-DOTATATE possess a comparable diagnostic accuracy for the detection of NET lesions, with 68Ga-DOTATOC having a potential advantage. The approximately 10-fold higher affinity for the sst2 of 68Ga-DOTATATE does not prove to be clinically relevant. Quite unexpectedly, SUVmax of 68Ga-DOTATOC scans tended to be higher than their 68Ga-DOTATATE counterparts.

Dissociating neural correlates for nouns and verbs

Dissociations in the ability to produce words of different grammatical categories are well established in neuropsychology but have not been corroborated fully with evidence from brain imaging. Here we report on a PET study designed to reveal the anatomical correlates of grammatical processes involving nouns and verbs. German-speaking subjects were asked to produce either plural and singular nouns, or first-person plural and singular verbs. Verbs, relative to nouns, activated a left frontal cortical network, while the opposite contrast (nouns-verbs) showed greater activation in temporal regions bilaterally. Similar patterns emerged when subjects performed the task with pseudowords used as nouns or as verbs. These results converge with findings from lesion studies and suggest that grammatical category is an important dimension of organization for knowledge of language in the brain.

Hybrid PET/MR Imaging of the Heart: Feasibility and Initial Results

PURPOSE To assess the feasibility of hybrid imaging of the heart with fluorine 18 fluorodeoxyglucose (FDG) on an integrated 3-T positron emission tomography (PET)/magnetic resonance (MR) imaging system. MATERIALS AND METHODS The present study was approved by the local institutional review board. Written informed consent was obtained from all patients before imaging. Twenty consecutive patients with myocardial infarction (n = 20) underwent cardiac PET/MR imaging examination. Ten patients underwent additional cardiac PET/computed tomography (CT) before PET/MR. Two-dimensional half-Fourier acquisition single-shot turbo spin-echo sequences, balanced steady-state free precession cine sequences, two-dimensional turbo inversion-recovery magnitude T2-weighted sequences, and late gadolinium-enhanced (LGE) segmented two-dimensional inversion-recovery turbo fast low-angle shot sequences were performed. According to the 17-segment model, PET tracer uptake, wall motion, and late gadolinium enhancement were visually assessed for each segment on a binary scale, and categorical intermethod agreement was calculated by using the Cohen κ. The maximum standardized uptake value was measured in corresponding myocardial locations on PET/CT and PET/MR images. RESULTS Agreement was substantial over all patients and segments between PET and LGE images (κ = 0.76) and between PET and cine images (κ = 0.78). In 306 segments, 97 (32%) were rated as infarcted on PET images, compared with 93 (30%) rated as infarcted on LGE images and with 90 (29%) rated as infarcted on cine images. In a subgroup of patients (n = 10) with an additional PET/CT scan, no significant difference in myocardial tracer uptake between PET/CT and PET/MR images was found (paired t test, P = .95). CONCLUSION Cardiac PET/MR imaging with FDG is feasible and may add complementary information in patients with ischemic heart disease.

SPECT/CT with 99mTc-MAA in Radioembolization with 90Y Microspheres in Patients with Hepatocellular Cancer

Radioembolization with 90Y microspheres is a novel treatment for hepatic tumors. Generally, hepatic arteriography and 99mTc-macroaggregated albumin (MAA) scanning are performed before selective internal radiation therapy to detect extrahepatic shunting to the lung or the gastrointestinal tract. Whereas previous studies have used only planar or SPECT scans, the present study used 99mTc-MAA SPECT/CT scintigraphy (SPECT with integrated low-dose CT) to evaluate whether SPECT/CT and additional diagnostic contrast-enhanced CT before radioembolization with 90Y microspheres are superior to SPECT or planar imaging alone for detection of gastrointestinal shunting. Methods: In a prospective study, we enrolled 58 patients (mean age, 66 y; SD, 12 y; 10 women and 48 men) with hepatocellular carcinoma who underwent hepatic arteriography and scintigraphy with 99mTc-MAA using planar imaging, SPECT, and SPECT with integrated low-dose CT of the upper abdomen (acquired with a hybrid SPECT/CT camera). The ability of the different imaging modalities to detect extrahepatic MAA shunting was compared. Patient follow-up of a mean of 180 d served as the standard of reference. Results: Gastrointestinal shunting was revealed by planar imaging in 4, by SPECT in 9, and by SPECT/CT in 16 of the 68 examinations. For planar imaging, the sensitivity for detection of gastrointestinal shunting was 25%, the specificity 87%, and the accuracy 72%. For SPECT without CT, the sensitivity was 56%, the specificity 87%, and the accuracy 79%. SPECT with CT fusion had a sensitivity of 100%, a specificity of 94%, and an accuracy of 96%. In 3 patients, MAA deposits in the portal vein could accurately be attributed to tumor thrombus only with additional information from contrast-enhanced CT. The follow-up did not show any gastrointestinal complications. Conclusion: SPECT with integrated low-dose CT using 99mTc-MAA is beneficial in radioembolization with 90Y microspheres because it increases the sensitivity and specificity of 99mTc-MAA SPECT when detecting extrahepatic arterial shunting. The overall low risk of gastrointestinal complications in radioembolization may therefore be further reduced by SPECT/CT.

Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging

Optoacoustic imaging strategies can be used to identify metastasis in excised lymph nodes and to determine SLN status in patients noninvasively. Imaging melanoma metastasis Avoiding invasive biopsy altogether, an imaging technique that relies on endogenous biomolecules to generate acoustic signals could be used to detect metastases in the body. Stoffels et al. devised a multispectral optoacoustic tomography (MSOT) approach that could image the pigment melanin in lymph nodes. Melanin would only be present in the lymph nodes if the primary cancer—melanoma—had spread to distant locations. The authors used handheld MSOT detectors and a near-infrared fluorophore (which pools in lymph nodes) to image metastases in patients, and complemented these optoacoustic images with ultrasound to gain a complete picture of each lymph node’s status. Such a noninvasive approach could reduce the number of patients subjected to sentinel lymph node surgical excision by “ruling out” metastasis. Sentinel lymph node (SLN) excision is included in various cancer guidelines to identify microscopic metastatic disease. Although effective, SLN excision is an invasive procedure requiring radioactive tracing. Novel imaging approaches assessing SLN metastatic status could improve or replace conventional lymph node excision protocols. In our first-in-human study, we used noninvasive multispectral optoacoustic tomography (MSOT) to image SLNs ex vivo and in vivo in patients with melanoma, to determine metastatic status. MSOT significantly improved the tumor metastasis detection rate in excised SLN (506 SLNs from 214 melanoma patients) compared with the conventional EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group protocol (22.9% versus 14.2%). MSOT combined with the near-infrared fluorophore indocyanine green reliably visualized SLNs in vivo in 20 patients, up to 5-cm penetration and with 100% concordance with 99mTc-marked SLN lymphoscintigraphy. MSOT identified cancer-free SLNs in vivo and ex vivo without a single false negative (189 total lymph nodes), with 100% sensitivity and 48 to 62% specificity. Our findings indicate that a noninvasive, nonradioactive MSOT-based approach can identify and determine SLN status and confidently rule out the presence of metastasis. The study further demonstrates that optoacoustic imaging strategies can improve the identification of SLN metastasis as an alternative to current invasive SLN excision protocols.

PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status

Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided.

68Ga-DOTATOC PET/CT and somatostatin receptor (sst1–sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax

PurposeBy targeting somatostatin receptors (sst) radiopeptides have been established for both diagnosis and therapy. For physiologically normal human tissues the study provides a normative database of maximum standardized uptake value (SUVmax) and sst mRNA.MethodsA total of 120 patients were subjected to diagnostic 68Ga-DOTATOC positron emission tomography (PET)/CT (age range 19–83 years). SUVmax values were measured in physiologically normal tissues defined by normal morphology, absence of surgical intervention and absence of metastatic spread during clinical follow-up. Expression of sst subtypes (sst1–sst5) was measured independently in pooled adult normal human tissue by real-time reverse transcriptase polymerase chain reaction (RT-PCR).ResultsSUVmax revealed a region-specific pattern (e.g., mean ± SD, spleen 31.1 ± 10.9, kidney 16.9 ± 5.3, liver 12.8 ± 3.6, stomach 7.0 ± 3.1, head of pancreas 6.2 ± 2.3, small bowel 4.8 ± 1.8, thyroid 4.7 ± 2.2, bone 3.9 ± 1.3, large bowel 2.9 ± 0.8, muscle 2.1 ± 0.5, parotid gland 1.9 ± 0.6, axillary lymph node 0.8 ± 0.3 and lung 0.7 ± 0.3). SUVmax was age independent. Gender differences were evident within the thyroid (female/male: 3.7 ± 1.6/5.5 ± 2.4, p < 0.001; Mann-Whitney U test) and the pancreatic head (5.5 ± 1.9/6.9 ± 2.2, p < 0.001). The sst mRNA was widely expressed and heterogeneous, showing sst1 to be most abundant. SUVmax values exclusively correlated with sst2 expression (r = 0.846, p < 0.001; Spearman rank correlation analysis), whereas there was no correlation of SUVmax with the expression of the other four subtypes.ConclusionIn normal human tissues 68Ga-DOTATOC imaging has been related to the expression of sst2 at the level of mRNA. The novel normative database may improve diagnostics, monitoring and therapy of sst-expressing tumours or inflammation on a molecular basis.

Depiction and characterization of liver lesions in whole body [18F]-FDG PET/MRI

OBJECTIVES To assess the value of PET/MRI with [(18)F]-FDG using a whole body protocol for the depiction and characterization of liver lesions in comparison to PET/CT. METHODS 70 patients (31 women, 39 men) with solid tumors underwent [(18)F]-FDG PET/CT and followed by an additional PET/MRI using an integrated scanner. Two readers rated the datasets (PET/CT; PET/MRI) regarding conspicuity of hepatic lesions (4-point ordinal scale) and diagnostic confidence (5-point ordinal scale). Median scores for lesion conspicuity and diagnostic confidence were compared using Wilcoxons rank sum test. Prior examinations, histopathology and clinical follow-up (116 ± 54 days) served as standard of reference. RESULTS 36 of 70 (51%) patients showed liver lesions. Using PET/CT and PET/MRI all patients with liver metastases could correctly be identified. A total of 97 lesions were found (malignant n=26; benign n=71). For lesion conspicuity significantly higher scores were obtained for PET/MRI in comparison to PET/CT (p<0.001). Significantly better performance for diagnostic confidence was observed in PET/MRI, both for malignant as for benign lesions (p<0.001). CONCLUSIONS PET/MRI, even in the setting of a whole body approach, provides higher lesion conspicuity and diagnostic confidence compared to PET/CT and may therefore evolve as an attractive alternative in oncologic imaging.

Simultaneous 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic neuroendocrine tumors: initial results.

ObjectivesThe aim of this pilot study was to demonstrate the potential of simultaneously acquired 68-Gallium-DOTA-D-Phe1-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison with 68Ga-DOTATOC PET/computed tomography (PET/CT) in patients with known gastroenteropancreatic neuroendocrine tumors (NETs). Materials and MethodsEight patients (4 women and 4 men; mean [SD] age, 54 [17] years; median, 55 years; range 25–74 years) with histopathologically confirmed NET and scheduled 68Ga-DOTATOC PET/CT were prospectively enrolled for an additional integrated PET/MRI scan. Positron emission tomography/computed tomography was performed using a triple-phase contrast-enhanced full-dose protocol. Positron emission tomography/magnetic resonance imaging encompassed a diagnostic, contrast-enhanced whole-body MRI protocol. Two readers separately analyzed the PET/CT and PET/MRI data sets including their subscans in random order regarding lesion localization, count, and characterization on a 4-point ordinal scale (0, not visible; 1, benign; 2, indeterminate; and 3, malignant). In addition, each lesion was rated in consensus on a binary scale (allowing for benign/malignant only). Clinical imaging, existing prior examinations, and histopathology (if available) served as the standard of reference. In PET-positive lesions, the standardized uptake value (SUVmax) was measured in consensus. A descriptive, case-oriented data analysis was performed, including determination of frequencies and percentages in detection of malignant, benign, and indeterminate lesions in connection to their localization. In addition, percentages in detection by a singular modality (such as PET, CT, or MRI) were calculated. Interobserver variability was calculated (Cohens &kgr;). The SUVs in the lesions in PET/CT and PET/MRI were measured, and the correlation coefficient (Pearson, 2-tailed) was calculated. ResultsAccording to the reference standard, 5 of the 8 patients had malignant NET lesions at the time of the examination. A total of 4 patients were correctly identified by PET/CT, with the PET and CT component correctly identifying 3 patients each. All 5 patients positive for NET disease were correctly identified by PET/MRI, with the MRI subscan identifying all 5 patients and the PET subscan identifying 3 patients. All lesions considered as malignant in PET/CT were equally depicted in and considered using PET/MRI. One liver lesion rated as “indetermined” in PET/CT was identified as metastasis in PET/MRI because of a diffusion restriction in diffusion-weighted imaging. Of the 4 lung lesions characterized in PET/CT, only 1 was depicted in PET/MRI. Of the 3 lymph nodes depicted in PET/CT, only 1 was characterized in PET/MRI. Interobserver reliability was equally very good in PET/CT (&kgr; = 0.916) and PET/MRI (&kgr; = 1.0). The SUVmax measured in PET/CT and in PET/MRI showed a strong correlation (Pearson correlation coefficient, 0.996). ConclusionsThis pilot study demonstrates the potential of 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic NET, with special advantages in the characterization of abdominal lesions yet certain weaknesses inherent to MRI, such as lung metastases and hypersclerotic bone lesions.

Integrated 18F-FDG PET/MR Imaging in the Assessment of Cardiac Masses: A Pilot Study

The objective of the present study was to evaluate whether integrated 18F-FDG PET/MR imaging could improve the diagnostic workup in patients with cardiac masses. Methods: Twenty patients were prospectively assessed using integrated cardiac 18F-FDG PET/MR imaging: 16 patients with cardiac masses of unknown identity and 4 patients with cardiac sarcoma after surgical therapy. All scans were obtained on an integrated 3-T PET/MR device. The MR protocol consisted of half Fourier acquisition single-shot turbo spin-echo sequence, cine, and T2-weighted images as well as T1-weighted images before and after injection of gadobutrol. PET data were acquired simultaneously with the MR scan after injection of 199 ± 58 MBq of 18F-FDG. Patients were prepared with a high-fat, low-carbohydrate diet in a period of 24 h before the examination, and 50 IU/kg of unfractionated heparin were administered intravenously 15 min before 18F-FDG injection. Results: Cardiac masses were diagnosed as follows: metastases, 3; direct tumor infiltration via pulmonary vein, 1; local relapse of primary sarcoma after surgery, 2; Burkitt lymphoma, 1; scar/patch tissue after surgery of primary sarcoma, 2; myxoma, 4; fibroelastoma, 1; caseous calcification of mitral annulus, 3; and thrombus, 3. The maximum standardized uptake value (SUVmax) in malignant lesions was significantly higher than in nonmalignant cases (13.2 ± 6.2 vs. 2.3 ± 1.2, P = 0.0004). When a threshold of 5.2 or greater was used, SUVmax was found to yield 100% sensitivity and 92% specificity for the differentiation between malignant and nonmalignant cases. T2-weighted hyperintensity and contrast enhancement both yielded 100% sensitivity but a weak specificity of 54% and 46%, respectively. Morphologic tumor features as assessed by cine MR imaging yielded 86% sensitivity and 92% specificity. Consent interpretation using all available MR features yielded 100% sensitivity and 92% specificity. A Boolean ‘AND’ combination of an SUVmax of 5.2 or greater with consent MR image interpretation improved sensitivity and specificity to 100%. Conclusion: In selected patients, 18F-FDG PET/MR imaging can improve the noninvasive diagnosis and follow-up of cardiac masses.