1660 Background: Arterial inflammation is the hallmark of atherogenesis and its complications. People living with human immunodeficiency virus (PLHIV) infection have an excess risk of atherosclerotic cardiovascular disease (ASCVD). 18F-FDG PET/CT is the most used modality to image arterial inflammation in ASCVD. There are several challenges with the use of 18F-FDG PET/CT for this purpose. In this study, we aimed to perform a head-to-head comparison of 18F-FDG PET/CT and [68Ga]Ga-pentixafor PET/CT for quantification of arterial inflammation in PLHIV.\n Methods: We prospectively recruited HIV-infected patients to undergo 18F-FDG PET/CT and [68Ga]Ga-pentixafor PET/CT within two weeks of each other. All recruited patients had been living with HIV infection for a minimum of 24 months and had completely suppressed HIV viremia on antiretroviral therapy. We obtained the maximum standardized uptake value (SUVmax) of arterial tracer uptake from the ascending aorta and carotid artery. We obtained the mean standardized uptake value (SUVmean) from the lumen of the superior vena cava and internal jugular vein for background correction. We computed the target-background-ratio for the ascending aorta and carotid artery by dividing the arterial SUVmax by the venous SUVmean. We used Bland and Altman plots to measure the level of agreement between tracer quantification parameters obtained on both scans.\n Results: A total of 12 patients were included with a mean age of 44.67 ± 7.62 years. The mean duration of HIV infection was 71.08 ± 37 months with a mean CD+ T-cell count of 522.17 ± 260.33 cells/µL, respectively. The mean activity of administered 18F-FDG was significantly higher than that of [68Ga]Ga-pentixafor (7.84 ± 1.17mCi and 4.70 ± 2.12mCi, p\u003c0.001). The median interval between the two scans was 2 days (range=1-11 days). We found a high level of agreement between the 18F-FDG PET-derived quantification variables and the [68Ga]Ga-pentixafor PET-derived variables in the aortic and carotid arterial beds with 91% to 100% of all measurements within the limits of agreement. There was a positive correlation between 18F-FDG PET and [68Ga]Ga-pentixafor PET-derived quantification variables obtained in the ascending aorta while similar parameters obtained in the carotid bed mostly showed negative correlation.\n Conclusions: There is a good level of agreement in the arterial tracer quantification variables obtained on 18F-FDG PET/CT and [68Ga]Ga-pentixafor PET/CT in PLHIV. This suggests that [68Ga]Ga-pentixafor may be used in the place of 18F-FDG PET/CT for the quantification of arterial inflammation.

People living with human immunodeficiency virus (PLHIV) have excess risk of atherosclerotic cardiovascular disease (ASCVD). Arterial inflammation is the hallmark of atherogenesis and its complications. In this study we aimed to perform a head-to-head comparison of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) and Gallium-68 pentixafor positron emission tomography/computed tomography [68Ga]Ga-pentixafor PET/CT for quantification of arterial inflammation in PLHIV. We prospectively recruited human immunodeficiency virus (HIV)-infected patients to undergo [18F]FDG PET/CT and [68Ga]Ga-pentixafor PET/CT within two weeks of each other. We quantified the levels of arterial tracer uptake on both scans using maximum standardized uptake value (SUVmax) and target–background ratio. We used Bland and Altman plots to measure the level of agreement between tracer quantification parameters obtained on both scans. A total of 12 patients were included with a mean age of 44.67 ± 7.62 years. The mean duration of HIV infection and mean CD+ T-cell count of the study population were 71.08 ± 37 months and 522.17 ± 260.33 cells/µL, respectively. We found a high level of agreement in the quantification variables obtained using [18F]FDG PET and [68Ga]Ga-pentixafor PET. There is a good level of agreement in the arterial tracer quantification variables obtained using [18F]FDG PET/CT and [68Ga]Ga-pentixafor PET/CT in PLHIV. This suggests that [68Ga]Ga-pentixafor may be applied in the place of [18F]FDG PET/CT for the quantification of arterial inflammation.

Preclinical and preliminary clinical evidence indicates that radiolabeled somatostatin (sst) receptor antagonists perform better than agonists in detecting neuroendocrine tumors (NETs). We performed a prospective phase I/II study to evaluate the sst receptor antagonist 68Ga-OPS202 (68Ga-NODAGA-JR11; NODAGA = 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid and JR11 = Cpa-c(dCys-Aph(Hor)-dAph(Cbm)-Lys-Thr-Cys)-dTyr-NH2)) for PET imaging. Here, we report the results of phase I of the study. Methods: Patients received 2 single 150-MBq intravenous injections of 68Ga-OPS202 3-4 wk apart (15 μg of peptide at visit 1 and 50 μg at visit 2). At visit 1, a dynamic PET/CT scan over the kidney was obtained during the first 30 min after injection, and static whole-body scans were obtained at 0.5, 1, 2, and 4 h after injection; at visit 2, a static whole-body scan was obtained at 1 h. Blood samples and urine were collected at regular intervals to determine 68Ga-OPS202 pharmacokinetics. Safety, biodistribution, radiation dosimetry, and the most appropriate imaging time point for 68Ga-OPS202 were assessed. Results: Twelve patients with well-differentiated gastroenteropancreatic (GEP) NETs took part in the study. 68Ga-OPS202 cleared rapidly from the blood, with a mean residence time of 2.4 ± 1.1 min/L. The organs with the highest mean dose coefficients were the urinary bladder wall, kidneys, and spleen. The calculated effective dose was 2.4E-02 ± 0.2E-02 mSv/MBq, corresponding to 3.6 mSv, for a reference activity of 150 MBq. Based on total numbers of detected malignant lesions, the optimal time window for the scan was between 1 and 2 h. For malignant liver lesions, the time point at which most patients had the highest mean tumor contrast was 1 h. 68Ga-OPS202 was well tolerated; adverse events were grade 1 or 2, and there were no signals of concern from laboratory blood or urinalysis tests. Conclusion:68Ga-OPS202 showed favorable biodistribution and imaging properties, with optimal tumor contrast between 1 and 2 h after injection. Dosimetry analysis revealed that the dose delivered by 68Ga-OPS202 to organs is similar to that delivered by other 68Ga-labeled sst analogs. Further evaluation of 68Ga-OPS202 for PET/CT imaging of NETs is therefore warranted.

Radiolabeled somatostatin receptor (SSTR) antagonists have shown in vivo higher uptake in SSTR-expressing tumors than agonists. In this preclinical study, the SSTR2 antagonist OPS201 (DOTA-JR11; DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2]) labeled with Lu-177, Y-90, and In-111 was compared with the SSTR2 agonist Lu-177-DOTATATE. Methods: Biodistribution, pharmacokinetics, SPECT/CT, and dosimetry studies were performed to assess the bioequivalence of all radiotracers. Use of escalated peptide mass and nephroprotective agents were systematically investigated. Results: The tumor residence time was 15.6 h (13.4-17.7) for Lu-177-OPS201 (10 pmol) and 6.4 h (5.4-7.3) for Lu-177-DOTATATE, resulting in a 2.5-times-higher tumor dose for the antagonist than for the agonist (0.854 vs. 0.333 mGy/MBq for a 4-cm tumor). The overall tumor-to-kidney dose ratio was approximately 24% and 32% higher for Lu-177-OPS201 than for Y-90-OPS201 and Lu-177-DOTATATE, respectively. In-111-OPS201 had a biodistribution significantly different from Y-90-OPS201 and is therefore not a surrogate for Y-90-OPS201 dosimetry studies. Importantly, and in contrast to Lu-177-DOTATATE, injection of 10, 200, and 2,000 pmol of Lu-177-OPS201 did not cause any relevant tumor saturation, with tumor uptake 4 h after injection: 23.9, 24.9, and 18.8 percentage of injected activity per gram of tissue (%IA/g), respectively, for the antagonist (P > 0.05), as compared with 17.8, 12.0, and 9.9 %IA/g for the agonist (P, 0.05). Increasing the peptide mass of Lu-177-OPS201 from 10 to 200 pmol drastically decreased the effective dose from 0.0908 to 0.0184 mSv/MBq and decreased the uptake in the liver, bone marrow, and all SSTR2-expressing organs; thus, the therapeutic index improved considerably. Lysine and succinylated gelatine, alone or in combination, significantly reduced the renal dose of Lu-177-OPS201 compared with the control group, by 45%, 25%, and 40%, respectively (P < 0.05). The reduction was similar for 10 and 200 pmol, whereas lysine performed better than succinylated gelatine. Conclusion: Lu-177-OPS201 exhibits higher tumor uptake, longer tumor residence time, and improved tumor-to-kidney dose ratio compared with Lu-177-DOTATATE and Y-90-OPS201. Importantly, the mass-escalation study indicates that an optimized antagonist mass might further improve the safety window of peptide receptor radionuclide therapy by reducing the liver and bone marrow doses as well as the effective dose. Clinical studies are warranted to confirm the efficacy and advantageous toxicity profile of Lu-177-OPS201.

Radiolabeled somatostatin receptor (SSTR) antagonists have shown in vivo higher uptake in SSTR-expressing tumors than agonists. In this preclinical study, the SSTR2 antagonist OPS201 (DOTA-JR11; DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2]) labeled with 177Lu, 90Y, and 111In was compared with the SSTR2 agonist 177Lu-DOTATATE. Methods: Biodistribution, pharmacokinetics, SPECT/CT, and dosimetry studies were performed to assess the bioequivalence of all radiotracers. Use of escalated peptide mass and nephroprotective agents were systematically investigated. Results: The tumor residence time was 15.6 h (13.4–17.7) for 177Lu-OPS201 (10 pmol) and 6.4 h (5.4–7.3) for 177Lu-DOTATATE, resulting in a 2.5-times-higher tumor dose for the antagonist than for the agonist (0.854 vs. 0.333 mGy/MBq for a 4-cm tumor). The overall tumor–to–kidney dose ratio was approximately 24% and 32% higher for 177Lu-OPS201 than for 90Y-OPS201 and 177Lu-DOTATATE, respectively. 111In-OPS201 had a biodistribution significantly different from 90Y-OPS201 and is therefore not a surrogate for 90Y-OPS201 dosimetry studies. Importantly, and in contrast to 177Lu-DOTATATE, injection of 10, 200, and 2,000 pmol of 177Lu-OPS201 did not cause any relevant tumor saturation, with tumor uptake 4 h after injection: 23.9, 24.9, and 18.8 percentage of injected activity per gram of tissue (%IA/g), respectively, for the antagonist (P > 0.05), as compared with 17.8, 12.0, and 9.9 %IA/g for the agonist (P < 0.05). Increasing the peptide mass of 177Lu-OPS201 from 10 to 200 pmol drastically decreased the effective dose from 0.0908 to 0.0184 mSv/MBq and decreased the uptake in the liver, bone marrow, and all SSTR2-expressing organs; thus, the therapeutic index improved considerably. Lysine and succinylated gelatine, alone or in combination, significantly reduced the renal dose of 177Lu-OPS201 compared with the control group, by 45%, 25%, and 40%, respectively (P < 0.05). The reduction was similar for 10 and 200 pmol, whereas lysine performed better than succinylated gelatine. Conclusion: 177Lu-OPS201 exhibits higher tumor uptake, longer tumor residence time, and improved tumor–to–kidney dose ratio compared with 177Lu-DOTATATE and 90Y-OPS201. Importantly, the mass-escalation study indicates that an optimized antagonist mass might further improve the safety window of peptide receptor radionuclide therapy by reducing the liver and bone marrow doses as well as the effective dose. Clinical studies are warranted to confirm the efficacy and advantageous toxicity profile of 177Lu-OPS201.

Radiolabeled somatostatin (sst) receptor agonists are integral to the diagnosis of gastroenteropancreatic neuroendocrine tumors (NETs), but detection rates, especially of liver metastases, remain limited even with PET/CT. Ga-68-OPS202 (Ga-68-NODAGA-JR11; NODAGA = 1,4,7-triazacyclononane, 1-glutaric acid-4,7-acetic acid and JR11 = Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2)), a novel radiolabeled sst receptor antagonist with a high affinity for the sst(2) receptor, has the potential to perform better than sst receptor agonists. Here, we present the results of the phase II component of a phase I/II study that evaluated the sensitivity of Ga-68-OPS202, compared with the reference compound, Ga-68-DOTATOC (an sst receptor agonist), in PET imaging. Methods: Patients received a single 150-MBq intravenous injection of Ga-68-DOTATOC (15 mu g of peptide) and 2 single 150-MBq intravenous injections of Ga-68-OPS202 (15 mu g of peptide at visit 1 and 50 mu g at visit 2). Wholebody PET/CT acquisitions were performed 1 h after injection on the same calibrated PET/CT scanner. Diagnostic efficacy measures were compared against contrast medium-enhanced CT or MRI as the gold standard. Two independent masked experts read the scans, and both outcomes were combined for analysis. Results: Twelve consecutive patients with low-or intermediate-grade gastroenteropancreatic NETs took part in this prospective study. Image contrast for matched malignant liver lesions was significantly higher for the Ga-68-OPS202 scans than for the Ga-68-DOTATOC scan: the median of the mean tumor-to-background SUVmax ratios were significantly higher for 15 and 50 mu g of Ga-68-OPS202 (5.3 and 4.3, with interquartile ranges of 2.9-5.7 and 3.4-6.3 and P values of 0.004 and 0.008) than for Ga-68-DOTATOC (1.9, with an interquartile range of 1.4-2.9). The higher tumor-to-background ratio of Ga-68-OPS202 resulted not only in a higher detection rate of liver metastases but also in a significantly higher lesion-based overall sensitivity with the antagonist than with Ga-68-DOTATOC: 94% and 88% for 50 and 15 mu g of Ga-68-OPS202, respectively, and 59% for 15 mu g of Ga-68-DOTATOC (P, 0.001). Positive predictive values for Ga-68-OPS202 PET/CT and 68Ga-DOTATOC PET/CT were similar (similar to 98%). There were no significant differences in image contrast, sensitivity, or positive predictive values between the 2 Ga-68-OPS202 peptide doses, indicating a high reproducibility. Conclusion: Preliminary diagnostic efficacy data from this phase II study indicate that Ga-68-OPS202 has high sensitivity for the detection of gastroenteropancreatic NETs. Further studies in larger patient populations are warranted.

154 Objectives 68Ga-DOTATOC PET/CT is a reference method for imaging somatostatin receptor (sstr) expressing neuroendocrine tumors (NET). Presence and extent of metastases, especially liver metastases, have a high impact on patient management and prognosis. Our aim was to investigate safety and diagnostic accuracy of 68Ga-OPS202, a radiolabelled sstr antagonist for PET/CT imaging of gastroenteropancreatic (GEP) NET (ClinicalTrials.gov NCT02162446). Methods Twelve metastatic G1/G2 GEP-NET patients were enrolled in a prospective phase 1/2 imaging study to investigate two single doses of 68Ga-OPS202 (A: 15μg & B: 50μg) in comparison with 68Ga-DOTATOC PET/CT (10-20 μg). Scans were reviewed by 2 independent blinded readers (on- and off-site reader). Follow-up imaging up to 9 months and biopsy were used as standard of reference. Results 68Ga-OPS202 was very well tolerated without adverse reaction that required treatment. Both 68Ga-OPS202 doses showed lower uptake than 68Ga-DOTATOC in the normal liver, the pancreas and the gastro-intestinal (GI) tract (p Conclusions 68Ga-OPS202 is well tolerated, improves imaging contrast and tumor detection compared to 68Ga-DOTATOC PET/CT, especially in the liver. The lower GI and pancreatic uptake may increase the PET accuracy for detecting sites of primary tumors of GEP origin.

177Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of 177Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications.

335 Objectives To assess, compare and optimize the therapeutic index of the radiolabeled somatostatin (sst) receptor antagonist 177Lu-OPS201 vs 177Lu-DOTATATE (agonist). Translational aspects related to peptide receptor radionuclide therapy (PRRT) and imaging are addressed. Methods 177Lu-OPS201 and 177Lu-DOTATATE were compared head-to-head in 2 sst2-expressing xenograft models (HEK-hsst2 & AR42J) in vivo. Biodistribution, pharmacokinetic study and nanoSPECT/CT images were performed. The influence of increasing peptide mass and of octreotide was studied. Results Besides usual physiological pattern of uptake in sst-positive organs, higher tumor uptake (e.g. ~35%, 4h, p 0.05) but significant decrease of the background (except renal uptake), as demonstrated by nanoSPECT/CT images. On the contrary, tumor uptake of 177Lu-DOTATATE decreased by 30% (200pmol) or 45% (2000pmol) (p Conclusions Increased tumor uptake, prolonged residence time, favorable differential washout and optimized peptide mass improve the therapeutic index of 177Lu-OPS201 compared to 177Lu-DOTATATE. Interruption of sst-analogs before PRRT may not be needed when using radiolabeled antagonists.

266 Objectives To present the first clinical data on 68Ga-OPS202, a radiolabeled somatostatin (sst) receptor antagonist, for PET/CT imaging of gastroenteropancreatic neuroendocrine tumors (GEP-NET) (ClinicalTrials.gov NCT02162446). Methods Metastatic G1/G2 GEP-NET patients, with at least 1 tumor focus on previous 68Ga-DOTATOC PET/CT, were screened for eligibility in an open-label, micro-dosing study. Safety, biodistribution, dosimetry of two single doses of 68Ga-OPS202 (A: 15μg & B: 50μg) and preliminary efficacy in comparison with 68Ga-DOTATOC PET/CT were investigated. 68Ga-OPS202 doses were given within 3-4 weeks interval. All PET/CT were performed on the same scanner, >4 weeks after sst-analogs had been stopped and 1h after i.v. injection of the radiotracer. Results Twelve patients were recruited (7 male, 5 female). No serious adverse event (AE) or AE needing medical intervention related to 68Ga-OPS202 occurred. Patient 5 presented hypereosinophilia of undetermined origin after the first injection (mild, grade 2). Both 68Ga-OPS202 doses (A & B) showed significantly lower uptake in the liver (mean SUVmax±σ) 3.4±0.8 (A)/3.0±0.8 (B), in the spleen 11.5±5.1 (A)/10.3±3.0 (B) and the intestine 3.6±1.5 (A)/3.0±0.9 (B) vs 6.7±2.2, 27.9±11.5 and 5.5±1.2 respectively for 68Ga-DOTATOC (p 2-fold (mean±σ) 4.4±3.5 (A)/4.9±3.9 (B) vs 2.1±1.5 for 68Ga-DOTATOC resulting in a higher detection rate. Detection rate and reproducibility data of 68Ga-OPS202 PET/CT will be shown. Conclusions 68Ga-OPS202 is well tolerated and shows increased image contrast compared to 68Ga-DOTATOC PET/CT. The lower hepatic and intestinal uptake may increase the sensitivity and diagnostic confidence in staging GEP-NETs.

Background: Imaging of somatostatin receptor (sst)-positive tumors using Ga-labeled somatostatin analogs such as the sst2 subtype-specific Ga-DOTA-TOC or Ga-DOTATATE is current clinical standard. Analogs targeting more receptor subtypes, such as Ga-DOTA-NOC, may improve detection of heterogeneous tumors. We aim to develop and evaluate a new Ga-labeled PET imaging probe based on SOM230 (Pasireotide) highly affine for sst1, 2, 3 and 5.

1511 Objectives [68Ga]-DOTASOM is a new somatostatin analogue with high affinity towards somatostatin receptor subtypes sst 1,2,3, and 5 for PET imaging in patients with neuroendocrine tumors. We present the in vivo distribution in a pig model as a basis for human dosimetry. Methods All procedures involving animals were performed under a Danish Ministry of Justice license. [68Ga]-DOTASOM was produced in an E&Z Modular lab Pharmtracer system by reacting 35 nM DOTASOM precursor with 68Ga in sodium acetate buffer (pH4.4) at 95°C. In vivo biodistribution and dosimetry studies were performed in anesthetized Danish Landrace pigs (3 female, 2 male, age: 3 - 4 month, average weight: 36.5kg) applying a series of 10 whole body PET/CT scans (Siemens Biograph 64). The physiological parameters were monitored and, if necessary, corrected during the scans. 10 arterial blood samples were taken for metabolite analysis. Time-activity curves and residence times were assessed for organs showing visible uptake. Based on these data a dose assessment was performed using OLINDA. Results The applied radiochemical procedure yielded sufficient amounts of [68Ga]-DOTASOM (RCP>95%). After injection (mean activity: 136 MBq), clearance of [68Ga]-DOTASOM from the body was characterized by fast renal excretion (t½ = 1.5 min), followed by slow clearance with t½ ≈ t½ of 68Ga. There was no visible uptake in the spleen. The highest organ residence times were observed in the bladder, liver and kidneys. The effective dose was estimated to 4.1*10-2mSv/MBq; organs with the highest absorbed doses were bladder, kidneys, testes and liver. Conclusions In vivo distributions and absorbed doses are generally comparable to those obtained for other somatostatin receptor ligands and should be no hindrance for human applications