Radiolabeled bicyclic somatostatin-based analogs: a novel class of potential radiotracers for SPECT/PET of neuroendocrine tumors

A variety of radiolabeled somatostatin analogs have been developed for targeting of somatostatin receptor (sst)-positive tumors. Bicyclic somatostatin-based radiopeptides have not been studied yet. Hypothesizing that the introduction of conformational constraints may lead to receptor subtype selectivity or may help to delineate structural features determining pansomatostatin potency, we developed and evaluated first examples of this new class of potential radiotracers for imaging or therapy of neuroendocrine tumors.

Bombesin antagonist-based radioligands for translational nuclear imaging of gastrin-releasing peptide receptor-positive tumors

Bombesin receptors are overexpressed on a variety of human tumors. In particular, the gastrin-releasing peptide receptor (GRPr) has been identified on prostate and breast cancers and on gastrointestinal stromal tumors. The current study aims at developing clinically translatable bombesin antagonist-based radioligands for SPECT and PET of GRPr-positive tumors.

A self-developed and constructed robot for minimally invasive cochlear implantation

Conclusion: A robot built specifically for stereotactic cochlear implantation provides equal or better accuracy levels together with a better integration into a clinical environment, when compared to existing approaches based on industrial robots. Objectives: To evaluate the technical accuracy of a robotic system developed specifically for lateral skull base surgery in an experimental setup reflecting the intended clinical application. The invasiveness of cochlear electrode implantation procedures may be reduced by replacing the traditional mastoidectomy with a small tunnel slightly larger in diameter than the electrode itself. Methods: The end-to-end accuracy of the robot system and associated image-guided procedure was evaluated on 15 temporal bones of whole head cadaver specimens. The main components of the procedure were as follows: reference screw placement, cone beam CT scan, computer-aided planning, pair-point matching of the surgical plan, robotic drilling of the direct access tunnel, and post-operative cone beam CT scan and accuracy assessment. Results: The mean accuracy at the target point (round window) was 0.56 ± 41 mm with an angular misalignment of 0.88 ± 0.41°. The procedural time of the registration process through the completion of the drilling procedure was 25 ± 11 min. The robot was fully operational in a clinical environment.

Tuberculosis in antiretroviral treatment programs in lower income countries: availability and use of diagnostics and screening

OBJECTIVES In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries. METHODS AND FINDINGS We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%). CONCLUSIONS Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge.

Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study

BACKGROUND Small benign insulinomas are hard to localise, leading to difficulties in planning of surgical interventions. We aimed to prospectively assess the insulinoma detection rate of single-photon emission CT in combination with CT (SPECT/CT) with a glucagon-like peptide-1 receptor avid radiotracer, and compare detection rates with conventional CT/MRI techniques. METHODS In our prospective imaging study, we enrolled adults aged 25-81 years at centres in Germany, Switzerland, and the UK. Eligible patients had proven clinical and biochemical endogenous hyperinsulinaemic hypoglycaemia and no evidence for metastatic disease on conventional imaging. CT/MRI imaging was done at referring centres according to standard protocols. At three tertiary nuclear medicine centres, we used whole body planar images and SPECT/CT of the abdomen up to 168 h after injection of (111)In-[Lys40(Ahx-DTPA-(111)In)NH2]-exendin-4 ((111)In-DTPA-exendin-4) to identify insulinomas. Consenting patients underwent surgery and imaging findings were confirmed histologically. FINDINGS Between Oct 1, 2008, and Dec 31, 2011, we recruited 30 patients. All patients underwent (111)In-DTPA-exendin-4 imaging, 25 patients underwent surgery (with histological analysis), and 27 patients were assessed with CT/MRI. (111)In-DTPA-exendin-4 SPECT/CT correctly detected 19 insulinomas and four additional positive lesions (two islet-cell hyperplasia and two uncharacterised lesions) resulting in a positive predictive value of 83% (95% CI 62-94). One true negative (islet-cell hyperplasia) and one false negative (malignant insulinoma) result was identified in separate patients by (111)In-DTPA-exendin-4 SPECT/CT. Seven patients (23%) were referred to surgery on the basis of (111)In-DTPA-exendin-4 imaging alone. For 23 assessable patients, (111)In-DTPA-exendin-4 SPECT/CT had a higher sensitivity (95% [95% CI 74-100]) than did CT/MRI (47% [27-68]; p=0·011). INTERPRETATION (111)In-DTPA-exendin-4 SPECT/CT could provide a good second-line imaging strategy for patients with negative results on initial imaging with CT/MRI. FUNDING Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.

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.