68 Ga-Prostate-Specific Membrane Antigen PET/CT in Ovarian Tumors : Potential to Differentiate Benign and Malignant Tumors Before Surgery: A Preliminary Report.

PURPOSE OF THE REPORT: Ovarian cancer is usually diagnosed in an advanced stage of disease due to the absence of specific symptoms and a lack of sensitive diagnostic methods. Prostate-specific membrane antigen (PSMA) is expressed on prostate cancer cells but can be found in other tumors such as ovarian cancer.The aim of this pilot study was to evaluate the feasibility of using 68 Ga-PSMA-11 PET/CT in detection of ovarian neoplasm before surgical treatment. PATIENTS AND METHODS: Eight women with mean age of 56.0 ± 16.2 years were included in the study. All patients underwent transvaginal ultrasound followed by CT scan of the chest and abdomen as qualification for surgery. Within a 1-week interval, PET/CT was performed on a Siemens Biograph scanner, 60 minutes after injection of 2 MBq/kg 68 Ga-PSMA-11. RESULTS: In 3 cases (37.5%), the 68 Ga-PSMA-11 PET/CT was positive, whereas histological examination confirmed 2 serous ovarian cancer cases and 1 ovarian borderline tumor. The SUV max in the serous ovarian cancer was 8.7 and 4.1, and in the borderline ovarian tumor, it was 13.8. No correlation was found between antigen CA-125 level and 68 Ga-PSMA expression. Range of tumor SUV max was not correlated with stage of disease. The remaining 62.5% (5/8) were negative in 68 Ga-PSMA-11 PET/CT, and histopathology confirmed benign pelvic tumor. CONCLUSIONS: The initial experience supports the potential to use 68 Ga-PSMA-11 in ovarian cancer to differentiate malignant and benign tumors before surgery.This study was approved by the Ethical Committee of the Medical University of Warsaw (KB/2/A/2018).

Development and Validation of an Analytical HPLC Method to Assess Chemical and Radiochemical Purity of [68Ga]Ga-NODAGA-Exendin-4 Produced by a Fully Automated Method.

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in ß-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R-avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic ß-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [68Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a 68Ge/68Ga Generator (GalliaPharma®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 µg/mL) and [68Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [68Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5-0.75 µg/mL for both the analytes (NODAGA-exendin-4 and 68Ga-NODAGA-exendin-4), with a correlation coefficient (R2) for calibration curves equal to 0.999, average coefficients of variation (CV%) < 2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [68Ga]Ga-NODAGA-exendin-4 was linear with a R2 of 0.993 and CV% < 2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 µg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [68Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [68Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [68Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.

CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line Helicobacter pylori eradication.

Posttreatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate positron emission tomography (PET) with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow up biopsies for assessment of residual disease (noncomplete remission [CR]) after first-line Helicobacter pylori eradication. Forty-six post-H pylori eradication [68Ga]Pentixafor-PET/magnetic resonance imaging (MRI) examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard and showed CR in 6 cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive values of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r = 0.51 and r = 0.52 (P = .008 and P = .006). In summary, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after H pylori eradication.

Early differences in dynamic uptake of 68Ga-PSMA-11 in primary prostate cancer: A test-retest study.

INTRODUCTION: Dynamic PET/CT allows visualization of pharmacokinetics over the time, in contrast to static whole body PET/CT. The objective of this study was to assess 68Ga-PSMA-11 uptake in pathological lesions and benign tissue, within 30 minutes after injection in primary prostate cancer (PCa) patients in test-retest setting. MATERIALS AND METHODS: Five patients, with biopsy proven PCa, were scanned dynamically in list mode for 30 minutes on a digital PET/CT-scanner directly after an intravenous bolus injection of 100 MBq 68Ga-PSMA-11. Approximately 45 minutes after injection a static whole body scan was acquired, followed by a one bed position scan of the pelvic region. The scans were repeated approximately four weeks later, without any intervention in between. Semi-quantitative assessment was performed using regions-of-interest in the prostate tumor, bladder, gluteal muscle and iliac artery. Time-activity curves were extracted from the counts in these regions and the intra-patient variability between both scans was assessed. RESULTS: The uptake of the iliac artery and gluteal muscle reached a plateau after 5 and 3 minutes, respectively. The population fell apart in two groups with respect to tumor uptake: in some patients the tumor uptake reached a plateau after 5 minutes, whereas in other patients the uptake kept increasing, which correlated with larger tumor volumes on PET/CT scan. Median intra-patient variation between both scans was 12.2% for artery, 9.7% for tumor, 32.7% for the bladder and 14.1% for the gluteal muscle. CONCLUSION: Dynamic 68Ga-PSMA-11 PET/CT scans, with a time interval of four weeks, are reproducible with a 10% variation in uptake in the primary prostate tumor. An uptake plateau was reached for the iliac artery and gluteal muscle within 5 minutes post-injection. A larger tumor volume seems to be related to continued tumor uptake. This information might be relevant for both response monitoring and PSMA-based radionuclide therapies.

Biodistribution of 68Ga-NODA-Aminoglucose in Intact and Tumor-Bearing Mice.

We studied the biodistribution of 68Ga-NODA-aminoglucose (68Ga-NODA-AG) in normal mice and mice with experimental model of colon adenocarcinoma tumor. It was shown that 68Ga-NODA-aminoglucose was retained in the tumor for 3 h after injection and demonstrated high level of accumulation in the tumor. Rapid clearance of radioactivity from other organs was observed. The results suggest that 68Ga-NODA-aminoglucose is a promising agent for tumor visualization by positron emission tomography.

A Comparative Study of the Pharmacokinetics of Bis- and Pentaphosphonic Acids Labeled with Gallium-68 in Rats with Experimental Model of Bone Callus.

We analyzed biodistribution of 68Ga-labeled hydroxyethylidenediphosphonic acid (68Ga-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) (68Ga-DTPMP) in Wistar rats with experimental model of bone callus. It was shown that the content of 68Ga-DTPMP and 68Ga-HEDP in bone callus was ~1.5-fold higher than in intact femur. 68Ga-DTPMP was characterized by higher stability in vivo, higher uptake in the bone tissue, and lower uptake in others visceral organs in comparison with 68Ga-HEDP. Thus, 68Ga-DTPMP had more suitable pharmacokinetic properties than 68Ga-HEDP.

Preparation, radiolabeling with 99mTc and 67Ga and biodistribution studies of albumin nanoparticles covered with polymers. / Preparación, radiomarcaje con 99mTc y 67Ga y estudios de biodistribución de nanopartículas de albúmina con recubrimientos poliméricos.

OBJECTIVE: To optimize radiolabeling with 99mTc and 67Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration. MATERIAL AND METHODS: The nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation method and coated with 4 different polymers; HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99mTc was perfomed with 74 MBq of 99mTc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1mg/ml) and at different times (5, 10, 15, 30 and 60minutes) and temperatures (room temperature, 40°C and 60°C). Radiolabelling with 67Ga was perfomed by incubation of the nanoparticles with 37 MBq of 67Gallium chloride (obtained from commercial gallium-67 citrate) at different times (10 and 30minutes) and temperatures (room temperature, 30°C and 60°C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were perfomed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99mTc sodium pertechnetate and 67Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter. RESULTS: 99mTc labeling was carried out optimally with a tin concentration of 0.007mg/ ml for the GPM2 nanoparticles and 0.005mg / ml for the rest of the formulations, with a radiolabelling time of 10minutes at room temperature. In the case of 67Ga the label was optimized at 30° C temperature and 30minutes of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48hours of labeling (70% nanoparticles labeled with 99mTc and 90% those labeled with 67Ga). Biodistribution studies of nanoparticles 99mTc -GPM2 and 67Ga -NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24hours after intravenous administration. CONCLUSION: The labeling procedure with 99mTc and 67Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies.

Evaluation of a 68Ga-Labeled DOTA-Tetrazine as a PET Alternative to 111In-SPECT Pretargeted Imaging.

The bioorthogonal reaction between a tetrazine and strained transcyclooctene (TCO) has garnered success in pretargeted imaging. This reaction was first validated in nuclear imaging using an 111In-labeled 1,4,7,10tetraazacyclododecane1,4,7,10tetraacetic acid (DOTA)-linked bispyridyl tetrazine (Tz) ([111In]In-DOTA-PEG11-Tz) and a TCO functionalized CC49 antibody. Given the initial success of this Tz, it has been paired with TCO functionalized small molecules, diabodies, and affibodies for in vivo pretargeted studies. Furthermore, the single photon emission tomography (SPECT) radionuclide, 111In, has been replaced with the ß-emitter, 177Lu and α-emitter, 212Pb, both yielding the opportunity for targeted radiotherapy. Despite use of the 'universal chelator', DOTA, there is yet to be an analogue suitable for positron emission tomography (PET) using a widely available radionuclide. Here, a 68Ga-labeled variant ([68Ga]Ga-DOTA-PEG11-Tz) was developed and evaluated using two different in vivo pretargeting systems (Aln-TCO and TCO-CC49). Small animal imaging and ex vivo biodistribution studies were performed and revealed target specific uptake of [68Ga]Ga-DOTA-PEG11-Tz in the bone (3.7 %ID/g, knee) in mice pretreated with Aln-TCO and tumor specific uptake (5.8 %ID/g) with TCO-CC49 in mice bearing LS174 xenografts. Given the results of this study, [68Ga]Ga-DOTA-PEG11-Tz can serve as an alternative to [111In]In-DOTA-PEG11-Tz.

Combined 68Ga-NOTA-Evans Blue Lymphoscintigraphy and 68Ga-NOTA-RM26 PET/CT Evaluation of Sentinel Lymph Node Metastasis in Breast Cancer Patients.

In this study, we applied a new strategy to identify sentinel lymph node (SLN) metastasis by combining 68Ga-NOTA-Evans Blue (68Ga-NEB) for SLN mapping and 68Ga-NOTA-RM26 for LN metastasis detection in breast cancer patients. A total of 24 female patients with breast cancer diagnosed by core biopsy or suspected by mammography or ultrasonography were recruited and provided informed consent. All patients underwent 68Ga-NEB and 68Ga-NOTA-RM26 PET/CT imaging. Visual analysis of 68Ga-NEB PET/CT images was used to determine SLNs, and then compared with the 68Ga-NOTA-RM26 results and histopathological findings. SLNs were visualized in 24 of 24 patients (100.0%) within 4.0-10.0 (5.6 ± 1.4) min. All patients were pathologically diagnosed with breast cancer, and 12 patients had ipsilateral lymph node metastasis. By combining 68Ga-NEB and 68Ga-NOTA-RM26 images, 7/12 (58.3%) patients showed mild to intense uptake of 68Ga-NOTA-RM26 in SLNs, 1/12 patient (8.3%) had moderate uptake of 68Ga-NOTA-RM26 in the non-SLNs rather than SLN, indicating possible bypass lymphatic drainage, partially accounting for the false negatives in SLN biopsy during surgery. No false positives were found. The SUVmax of 68Ga-NOTA-RM26 activity in metastatic SLNs was significantly higher than that in non-metastatic SLNs (2.2 ± 2.3 vs 0.7 ± 0.1, P = 0.047). This study manifests the value of combination of 68Ga-NEB and 68Ga-NOTA-RM26 dual tracer PET/CT in preoperative evaluation of SLN metastasis in breast cancer patients, especially in those patients with lymphatic obstruction and bypass drainage. In general, positive 68Ga-NOTA-RM26 uptake in either SLN or other lymph nodes can apply lymph node dissection rather than intraoperative SLN biopsy.

A nanobody-based nuclear imaging tracer targeting dipeptidyl peptidase 6 to determine the mass of human beta cell grafts in mice.

AIMS/HYPOTHESIS: Type 1 diabetes is characterised by a progressive decline in beta cell mass. This is also observed following implantation of pancreatic islet allografts, but there is no reliable information regarding the time course of beta cell loss. This is due to the limited availability of non-invasive pancreatic islet imaging techniques. We have previously described that dipeptidyl peptidase 6 (DPP6) is an alpha and beta cell-specific biomarker, and developed a camelid antibody (nanobody '4hD29') against it. We demonstrated the possibility to detect DPP6-expressing cells by single-photon emission computed tomography (SPECT)/ computed tomography (CT), but the correlation between the number of cells grafted and the SPECT signal was not assessed. Here, we investigate whether the 4hD29 nanobody allows us to detect different amounts of human pancreatic islets implanted into immune-deficient mice. In addition, we also describe the adaptation of the probe for use with positron emission tomography (PET). METHODS: DPP6 expression was assessed in human samples using tissue arrays and immunohistochemistry. The effect of the 4hD29 nanobody on cell death and glucose-stimulated insulin secretion was measured in EndoC-ßH1 cells and in human islets using Hoechst/propidium iodide staining and an anti-insulin ELISA, respectively. We performed in vivo SPECT imaging on severe combined immunodeficient (SCID) mice transplanted with different amounts of EndoC-ßH1 cells (2 × 106, 5 × 106 and 10 × 106 cells), human islets (1000 and 3000) or pancreatic exocrine tissue using 99mTc-labelled 4hD29 nanobody. This DPP6 nanobody was also conjugated to N-chlorosuccinimide (NCS)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), radiolabelled with either 67Ga (SPECT) or 68Ga (PET) and used in a proof-of-principle experiment to detect DPP6-expressing cells (Kelly neuroblastoma) grafted in SCID mice. RESULTS: The DPP6 protein is mainly expressed in pancreatic islets. Importantly, the anti-DPP6 nanobody 4hD29 allows non-invasive detection of high amounts of EndoC-ßH1 cells or human islets grafted in immunodeficient mice. This suggests that the probe must be further improved to detect lower numbers of islet cells. The 4hD29 nanobody neither affected beta cell viability nor altered insulin secretion in EndoC-ßH1 cells and human islets. The conversion of 4hD29 nanobody into a PET probe was successful and did not alter its specificity. CONCLUSIONS/INTERPRETATION: These findings suggest that the anti-DPP6 4hD29 nanobody may become a useful tool for the quantification of human islet grafts in mice and, pending future development, islet mass in individuals with diabetes.

Diagnostic utility of Gallium-68-somatostatin receptor PET/CT in ectopic ACTH-secreting tumors: a systematic literature review and single-center clinical experience.

PURPOSE: Tumors causing ectopic Cushing's syndrome (ECS) are often not visible with conventional imaging. Gallium-68-DOTATATE, DOTATOC, and DOTANOC positron emission tomography/computed tomography (68Ga-SSTR PET/CT) reportedly exhibits greater sensitivity in identifying an ECS source, however, evidence is limited to mainly case reports and a few small retrospective studies. Previous systematic ECS imaging review has shown 68Ga-SSTR PET/CT sensitivity is similar to CT (81.8%) in histologically-proven cases and is 100% in covert-cases, however, the number of patients was small and no occult cases were reported. METHODS: We performed a systematic literature review of 68Ga-SSTR PET/CT use in ECS patients. We also report 6 consecutive patients with confirmed active and occult ECS who underwent 68Ga-DOTATATE PET/CT and were followed at our institution between 2014 and 2019. RESULTS: We identified 33 articles (23 case-reports, 4 case-series, 5 retrospective studies and 1 prospective study) detailing 68Ga-SSTR PET/CT in 69 ECS patients. Overall 68Ga-SSTR PET/CT sensitivity was 64.0%, while in histologically confirmed cases (67 lesions), sensitivity was 76.1%. There were two false-positives cases, both in the adrenal glands. In covert cases, 68Ga-SSTR PET/CT identified 50% of lesions. There were ten occult cases where all imaging failed to identify an adrenocorticotropic hormone source; source remains unknown. In our case series, 68Ga-DOTATATE PET/CT showed decreased uptake in pancreatic neuroendocrine tumor in one patient and did not help identify an ECS source in 5 patients. CONCLUSION: Both this systematic literature review, the largest to date, and our single- center experience demonstrate a lower than previously reported 68Ga-SSTR PET/CT sensitivity for ECS, especially in occult lesions. We suggest that the data on 68Ga-SSTR PET/CT in ECS is subject to publication bias, and false-negatives are likely underreported; it's diagnostic value for ECS needs further study.

Preclinical Evaluation of 68Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis.

Neurotensin receptor 1 (NTSR1) is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Specific noninvasive positron-emission tomography (PET) imaging probes may improve the diagnostic accuracy and the monitoring of therapy for patients with PDAC. Here, we report the use of the 68Ga-labeled neurotensin (NTS) analogue DOTA-NT-20.3 to image human PDAC in animal models and to discriminate tumors from pancreatitis. In addition to the preclinical study, two tissue microarray slides, constructed by small core biopsies (2-5) from standard paraffin-embedded tumor tissues, were used to confirm the high (78%) positivity rate of NTSR1 expression in human PDAC. PET imaging, biodistribution, blocking, and histology studies were performed in subcutaneous AsPC-1 pancreatic tumor-bearing mice. 68Ga-DOTA-NT-20.3 PET images showed rapid tumor uptake and high contrast between the tumor and background with a fast blood clearance and a moderate accumulation in the kidneys. Ex vivo biodistribution showed low uptake in normal pancreas (0.22% IA/g) and in the remaining organs at 1 h postinjection, kidney retention (5.38 ± 0.54% IA/g), and fast clearance from blood and confirmed high uptake in tumors (5.28 ± 0.93% IA/g), leading to a tumor-to-blood ratio value of 6 at 1 h postinjection. The significant decrease of tumor uptake in a blocking study demonstrated the specificity of 68Ga-DOTA-N-T20.3 to target NTSR1 in vivo. PET imaging was also conducted in an orthotopic xenograft model that allows tumors to grow in their native microenvironment and in an experimental pancreatitis model generated by caerulein injections. As opposed to 2-[18F]fluoro-deoxyglucose, 68Ga-DOTA-NT-20.3 distinguishes PDAC from pancreatitis. Thus, 68Ga-DOTA-NT-20.3 is a promising PET imaging probe for imaging PDAC in humans.

NEUTRON FLUX DISTRIBUTION IN THE RADIOISOTOPES TARGET ROOMS AND MAZE IN SYRIAN CYCLOTRON.

Gold activation foils were used in this work to measure thermal, epithermal and fast neutron fluxes in the 18F, 123I, (201Tl, 67Ga) production units in Syrian cyclotron. The neutron flux distribution around the targets were determined. It shows that, the maze thermalizes the fast neutrons and reduces the flux about four orders of magnitudes. The results can be adopted by medical centers to identify radioactive hot spots and develop radiation protection.

Unambiguous detection of atherosclerosis using bioorthogonal nanomaterials.

The importance of atherosclerosis is driving research to create improved diagnostic tools based on molecular imaging. Pretargeted imaging is the use of bioorthogonal probes that selectively accumulate upon reaction with a pre-modified biomolecule in vivo. To date, this very promising approach has not been applied to atherosclerosis. Neither has been the use of a single nano-radiomaterial for PET / T1-MR imaging of atherosclerosis. Here, we synthesized bioorthogonal nano-radiomaterials for in vivo pretargeted molecular imaging in a mouse model of atherosclerosis. Based on tetrazine-ligation, these functionalized 68Ga iron oxide nano-radiomaterials provide simultaneous PET and T1-MRI signals and selectively accumulate in atherosclerotic plaques in mice sequentially injected with trans-cyclooctene-modified antibodies against oxidized LDL followed by the hybrid nano-radiomaterial. Our results demonstrate the ability of this approach to unambiguously detect atherosclerosis. Furthermore, we show the first example of how hybrid imaging can be used for pretargeted bioorthogonal molecular imaging with nanomaterials.

Experimental validation of estimated spatially variant radioisotope-specific point spread functions using published positron range simulations and fluorine-18 measurements.

In this work we compare spatially variant radioisotope-specific point spread functions (PSFs) derived from published positron range data with measured data using a high resolution research tomograph (HRRT). Spatially variant PSFs were measured on a HRRT for fluorine-18, carbon-11 and gallium-68 using an array of printed point sources. For gallium-68, this required modification of the original design to handle its longer positron range. Using the fluorine-18 measurements and previously published data from Monte-Carlo simulations of positron range, estimated PSFs for carbon-11 and gallium-68 were calculated and compared with experimental data. A double 3D Gaussian function was fitted to the estimated and measured data and used to model the spatially varying PSFs over the scanner field of view (FOV). Differences between the measured and estimated PSFs were quantified using the full-width-at-half-maximum (FWHM) and full-width-at-tenth-maximum (FWTM) in the tangential, radial and axial directions. While estimated PSFs were generally in agreement with the measured PSFs over the entire FOV better agreement was observed (FWHM and FWTM differences of less than 10%) when using one of the two sets of positron range simulations, especially for gallium-68 and for the FWTM. Spatially variant radioisotope specific PSFs can be accurately estimated from fluorine-18 measurements and published positron range data. We have experimentally validated this approach for carbon-11 and gallium-68, and such an approach may be applicable to other radioisotopes such as oxygen-15 for which measurements are not practical.

Gallium-68: methodology and novel radiotracers for positron emission tomography (2012-2017).

Commercial 68Ge/68Ga generators provide a means to produce positron emission tomography agents on site without use of a cyclotron. This development has led to a rapid growth of academic literature and patents ongallium-68 (68Ga). As 68Ga positron emission tomography agents usually involve a targeting moiety attached to a metal chelator, the development lends itself to the investigation of theragnostic applications; the 68Ga-based diagnostic is utilized to determine if the biological target is present and, if so, a therapeutic isotope (e.g., 177Lu, 225Ac) can be complexed with the same scaffold to generate a corresponding radiotherapeutic. This review considers patents issued between 2012 and 2017 that contain a 68Ga-labeled molecule indexed by Chemical Abstract Services (a division of the American Chemical Society).

68Ga-NOTA-ubiquicidin fragment for PET imaging of infection: From bench to bedside.

This study explores the possibility of formulation of a cold kit for fast and easy preparation of a PET radiopharmaceutical, 68Ga-NOTA-UBI (29-41) for clinical translation. In this study, Circular dichroism (CD) spectroscopy to study conformation of NOTA-UBI (29-41) and its comparison with conformation of UBI (29-41) was done. Pharmaceutical grade cold kits of NOTA-UBI (29-41) were formulated for radiolabeling with 68Ga and necessary quality control tests were carried out. 68Ga-NOTA-UBI (29-41) could be prepared in >90% radiochemical yield and radiochemical purity using cold kits of NOTA-UBI (29-41). In vitro and in vivo evaluation of 68Ga-NOTA-UBI (29-41) was done to demonstrate specificity of the agent for imaging infection. Kits were utilized for preparation of patient dose of 68Ga-NOTA-UBI (29-41). Simple instant thin layer chromatography (ITLC) method for estimating radiolabeling yield of 68Ga-NOTA-UBI (29-41) at hospital radiopharmacy was demonstrated. Clinical evaluation was done in patients with suspected infection. 148-185 MBq of 68Ga-NOTA-UBI (29-41) was injected intravenously in three patients. 68Ga-NOTA-UBI (29-41) uptake could clearly delineate infection foci from non target normal tissues. This is the first report on formulation of a cold kit of NOTA-UBI (29-41) for preparation of 68Ga labeled NOTA-UBI(29-41) at hospital radiopharmacy for infection imaging. Initial clinical evaluation reveal it to be a prospective agent for imaging infection.

Value of post-therapy 177Lu-PSMA images for accurate interpretation of therapy response with 68Ga-PSMA PET/CT. / Valor de las imágenes de 177Lu-PSMA post-terapia para una interpretación precisa de la respuesta a la terapia con PET/TC con 68Ga-PSMA.

A 54-year-old man with progressive prostate cancer underwent a 68Ga-PSMA PET/CT, which showed lymph node and bone metastases. After 2-cycles of 177Lu-PSMA therapy, the repeated 68Ga-PSMA PET/CT showed decreased radiotracer uptake in lymph node and bones metastases, but there were new lesions which may be compatible with progression or tumour sink-effect. A review of 177Lu-PSMA-therapy images revealed that new lesions in the second PET/CT were the metastatic lesions that progressed after the first PET/CT, and subsequently showed a good response. The patient received additional cycles of 177Lu-PSMA therapy, and the disease regressed further, with a PSA of 0.06ng/ml. Response evaluation of new therapeutic diagnostics (theranostic) agents needs a review of not only diagnostic PET/CT images, but also post-therapy images and laboratory results.

68Ga activity calibrations for nuclear medicine applications in Cuba.

The realization and dissemination of the 68Ga activity measurement unit in Cuba is presented. Firstly, the implementation of the Triple to Double Coincidence Ratio (TDCR) method is described for the calibration of the activity concentration of a 68Ga solution using a Hidex™ commercial liquid scintillation counter and a FORTRAN code developed for the calculation of the 68Ga counting efficiencies in the given measurement system. The relative expanded uncertainty (k = 2) associated with the 68Ga activity concentration obtained with the TDCR method is equal to 2%. With the aim to validate this measurement uncertainty estimate, the method is also applied to an Amersham standard solution of 22Na - a positron emitter with a similar decay mode to the 68Ga disintegration scheme from the point of view of type of emitted particles detected in the measurement system. The observed difference between the measured 22Na activity concentration by the TDCR method and the corresponding reference value traceable to NIST is equal to 0.16%. Outcomes of transferring the 68Ga activity standard, realized with the TDCR method, to the secondary standard radionuclide calibrator Capintec CRC™ 15R and to three radionuclide calibrators used for 68Ga PET applications in a hospital are also shown.