Radionuclide Cisternography with [64Cu]Cu-DOTA.

Radionuclide cisternography (RNC) is a method for conducting imaging of the cerebrospinal system and can be used to identify cerebrospinal fluid leaks. So far, RNC has commonly employed radiopharmaceutical agents suitable only for single-photon emission tomography techniques, which are thus lacking in terms of image resolution and can potentially lead to false-negative results. Therefore, [64Cu]Cu-DOTA was investigated as an alternative radiopharmaceutical for RNC, employing positron emission tomography (PET) instead of single-photon emission tomography. A formulation of [64Cu]Cu-DOTA was produced according to the guidelines for good manufacturing practice. The product met the requirements of agents suitable for intrathecal application. [64Cu]Cu-DOTA was administered to a patient and compared to the approved scintigraphic RNC agent, [111In]In-DTPA. While no cerebrospinal fluid leak was detected with [111In]In-DTPA, [64Cu]Cu-DOTA RNC exhibited a posterolateral leak between the vertebral bodies C1 and C2. Thus, in this patient, PET RNC with [64Cu]Cu-DOTA was superior to RNC with [111In]In-DTPA. Since radiopharmaceuticals have a very good safety profile regarding the occurrence of adverse events, PET RNC with [64Cu]Cu-DOTA may become an attractive alternative to scintigraphic methods, and also to computed tomography or magnetic resonance imaging, which often require contrast agents, causing adverse events to occur much more frequently.

67 Ga-PSMA I&T for Radioguided Surgery of Lymph Node Metastases in Patients With Biochemical Recurrence of Prostate Cancer.

PURPOSE: Radioguided lymph node dissection in patients with prostate cancer, and suffering from biochemical recurrence has been described thoroughly during the past few years. Several prostate-specific membrane antigen (PSMA)-directed ligands labeled with 111 In, 99m Tc, and 68 Ga have been published; however, limitations regarding availability, short half-life, high costs, and unfavorable high energy might restrict frequent use. This study aims at introducing 67 Ga as a promising radionuclide for radioguided surgery. METHODS: Retrospective analysis was performed on 6 patients with 7 PSMA-positive lymph node metastases. 67 Ga-PSMA I&T (imaging and therapy) was synthesized in-house and intravenously applied according to §13 2b of the German Medicinal Products Act. Radioguided surgery was performed 24 hours after injection of 67 Ga-PSMA I&T using a gamma probe. Patient urine samples were collected. Occupational and waste dosimetry was performed to describe hazards arising from radiation. RESULTS: 67 Ga-PSMA application was tolerated without adverse effects. Five of 7 lymph nodes were detected on 22-hour SPECT/CT in 4 of 6 patients. During surgery, all 7 lymph node metastases were identified by positive gamma probe signal. Relevant accumulation of 67 Ga was observed in lymph node metastases (32.1 ± 15.1 kBq). Histology analysis of near-field lymph node dissection revealed more lymph node metastases than PET/CT (and gamma probe measurements) identified. Waste produced during inpatient stay required decay time of up to 11 days before reaching exemption limits according to German regulations. CONCLUSIONS: Radioguided surgery using 67 Ga-PSMA I&T is a safe and feasible option for patients suffering from biochemical recurrence of prostate cancer. 67 Ga-PSMA I&T was successfully synthesized according to Good Manufacturing Practice guidelines. Radioguided surgery with 67 Ga-PSMA I&T does not lead to relevant radiation burden to urology surgeons and represents a novel interdisciplinary approach in nuclear medicine and urology.

Automated GMP Production and Preclinical Evaluation of [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA.

[68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA are two novel radiotracers suitable for functional PET liver imaging. Due to their specific liver uptake and biliary excretion, the tracers may be applied for segmental liver function quantification, gall tree imaging and the differential diagnosis of liver nodules. The purpose of this study was to investigate problems that occurred initially during the development of the GMP compliant synthesis procedure and to evaluate the tracers in a preclinical model. After low radiolabeling yields were attributed to precursor instability at high temperatures, an optimized radiolabeling procedure was established. Quality controls were in accordance with Ph. Eur. requirements and gave compliant results, although the method for the determination of the 68Ga colloid is partially inhibited due to the presence of a radioactive by-product. The determination of logP revealed [68Ga]Ga-TEoS-DAZA (ethoxy bearing) to be more lipophilic than [68Ga]Ga-TMoS-DAZA (methoxy bearing). Accordingly, biodistribution studies in an in ovo model showed a higher liver uptake for [68Ga]Ga-TEoS-DAZA. In dynamic in ovo PET imaging, rapid tracer accumulation in the liver was observed. Similarly, the activity in the intestines rose steadily within the first hour p.i., indicating biliary excretion. As [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA can be prepared according to GMP guidelines, transition into the early clinical phase is now possible.

In-ovo imaging using ostrich eggs: Biomagnetism for detection of cardiac signals and embryonal motion.

In-ovo imaging using ostrich eggs has been described as a potential alternative to common animal testing. The main advantage is its independence from small animal imaging devices as ostrich eggs provide good image quality on regular CT, MRI, or PET used in examinations of humans. However, embryonal motion during dynamic imaging studies produce artifacts. The aims of this study were (1) to explore the feasibility of biomagnetism to detect cardiac signals and embryonal motion and to use these findings (2) to investigate the effect of isoflurane anesthesia on ostrich embryos. A standard magnetoencephalography developed for brain studies was used to detect embryonal signals of ostrich eggs on developmental day 34. Signals were instantly shown on a screen and data were also postprocessed. For assessing the effects of anesthesia, nine ostrich eggs were investigated using isoflurane 6% for 90 min. Biomagnetic signals were recorded simultaneously. A control group consisting of eight different ostrich eggs was also investigated. Cardiac signals similar to electrocardiography were observed in all eggs. Postprocessing revealed frequent motion of embryos without anesthesia. The exposure to isoflurane led to a significant decrease in motion signals in 9/9 ostrich embryos after 8 min. Motion was significantly reduced in the isoflurane group versus control group. There were no isoflurane-related deaths. This study shows that biomagnetism is feasible to detect cardiac signals and motion of ostrich embryos in-ovo. Application of isoflurane is safe and leads to a rapid decrease in embryonal motion, which is an important prerequisite for the implementation of in-ovo imaging using ostrich eggs.

Design, construction, and validation of a hybrid phantom for nuclear medicine and ultrasound fusion imaging.

Fusion imaging with nuclear medicine and ultrasound via mobile handheld gamma cameras has been recently introduced, however a phantom for the registration accuracy of this fusion approach is still lacking. We developed a hybrid phantom, consisting of poly-methyl methacrylate and exchangeable ultrasound (US) compatible windows made of silicone or poly-vinyl chloride. A standard balloon catheter, filled with a mixture of [99mTc]TcO4 and water, was positioned at the center of the water-filled phantom. This approach enabled an objective measurement of the registration accuracy.

Stitching of sensor-navigated 3D ultrasound datasets for the determination of large thyroid volumes - a phantom study.

AIMS: Thyroid volume has to be measured in goiters prior to radioiodine treatment to calculate the needed amount of radioactivity. Modern clinical equipment for ultrasonography shows the trend to smaller probes, so that larger goiters do not fit any longer into the probe's field of view. This study evaluated the feasibility and accuracy of stitching procedures applied to thyroid volumetric analysis performed using three-dimensional ultrasound (3D-US). MATERIAL AND METHODS: Ad hoc thyroid phantoms of different shapes (regular, nodular, thickened isthmus) and volumes (ranging between 50 and 400 mL) were developed. In 15 such phantoms the left and right lobes were separately scanned, and the 3D-US datasets were then assembled (stitched) using predefined landmarks and dedicated software. Volumetric analysis was then assessed via a conventional ellipsoid model (em) and manual tracing (mt). The correlation of measured and reference volumes was determined using Pearson's correlation coefficients and Bland and Altman limits of agreement. RESULTS: The results showed a high level of agreement (with correlation coefficients ranging from 0.974 to 0.999) for all shapes and volumes tested, including the largest volume of 400 mL. The mt method, although more time consuming, proved superior to the em. CONCLUSIONS: Stitching-mediated thyroid volumetric analysis is accurate, and its clinical performance should be investigated in future studies.

99mTc-Pertechnetate-SPECT/US Hybrid Imaging Enhances Diagnostic Certainty Compared With Conventional Thyroid Imaging With Scintigraphy and Ultrasound.

Evaluation of thyroid ultrasound and Tc-pertechnetate scintigraphy side by side frequently produces ambiguous results regarding the correct assignment of anatomy and functionality of a nodule. We describe the usefulness of Tc-pertechnetate-SPECT/US-fusion imaging. A 75-year-old woman was referred for exclusion of cold nodules. After conventional diagnostics (in vitro thyroid parameters, B mode-US, planar Tc-pertechnetate-thyroid scintigraphy), a SPECT was performed using a conventional gamma camera. The SPECT data set was transferred to an ultrasound device (LOGIQ E9), and sensor-navigated 3D ultrasound was performed. Both data sets (SPECT/US) were fused in real time, revealing the exact functional state of multiple nodules.

The Use of Ostrich Eggs for In Ovo Research: Making Preclinical Imaging Research Affordable and Available.

In ovo studies are a valuable option in preclinical research, but imaging studies are severely limited by the costs of dedicated equipment needed for small-sized eggs. We sought to verify the feasibility of using larger, ostrich, eggs (Struthio camelus) for imaging on the PET/CT scanners used for routine clinical investigations. Methods: Ostrich eggs were incubated until shortly before hatching, prepared for intravitelline venous injection of contrast medium or radiotracer, and imaged using native CT, contrast-enhanced CT, and PET/CT. Any technical adaptations that were needed to improve the outcome were noted. Results: Of the 34 eggs initially incubated, 12 became fully available for imaging of embryonal development. In ovo imaging with conventional PET/CT not only was feasible but also provided images of good quality, including on dynamic PET imaging. Conclusion: In ovo imaging with ostrich eggs and routine clinical scanners may allow broader application of this field of preclinical research, obviating costly dedicated equipment and reducing the number of animals needed for classic animal research. Further experiments are warranted to refine this novel approach, especially to reduce motion artifacts and improve monitoring of viability.