Search

Purpose: [68Ga]Trishydroxypyridinone (THP)-prostate-specific membrane antigen (PSMA) is a novel tracer that can be labeled in one step by cold reconstitution of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea-glutamate (KuE) motif. The aim of this study was to evaluate the human imaging characteristics of [68Ga]THP-PSMA.Procedures: [68Ga]THP-PSMA positron emission tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with biochemical recurrence after radical prostatectomy for prostate cancer. Urinary and biliary excretion and tumor lesion uptake were quantified using standardized uptake values (SUVs). Imaging characteristics were assessed in terms of non-target organ uptake, background activity, target-to-background ratios (TBRs) of tumor lesions, and frequency of bladder halo artifacts. Findings were compared to a matched cohort of 25 patients undergoing PET/CT with the established agent [68Ga]PSMA I&T.Results: Physiologic uptake of [68Ga]THP-PSMA was significantly lower in salivary glands (P < 0.0001), liver (P < 0.0001), spleen (P < 0.0001), and kidneys (P < 0.0001) than with [68Ga]PSMA I&T. While biliary tracer excretion of [68Ga]THP-PSMA was negligible, urinary tracer excretion of [68Ga]THP-PSMA was fast, and significantly higher than for [68Ga]PSMA I&T, contributing to a higher frequency of bladder artifacts. Malignant lesion uptake of [68Ga]THP-PSMA assessed as either SUV or TBR was significantly lower than with [68Ga]PSMA I&T.Conclusion: [68Ga]THP-PSMA yields suitable in vivo uptake characteristics. The simplified synthesis method for [68Ga]THP-PSMA may facilitate wider application and higher patient throughput with PSMA imaging. However, direct intraindividual comparison studies are needed to assess the relative performance of [68Ga]THP-PSMA vs other PSMA ligands in terms of clinical detection rate and image quality. [ABSTRACT FROM AUTHOR]

Purpose: [68Ga]Tris(hydroxypyridinone)(THP)-PSMA is a novel radiopharmaceutical for one-step kit-based radiolabelling, based on direct chelation of 68Ga3+ at low concentration, room temperature and over a wide pH range, using direct elution from a 68Ge/68Ga-generator. We evaluated the clinical detection rates of [68Ga]THP-PSMA PET/CT in patients with biochemically recurrent prostate cancer after prostatectomy.Methods: Consecutive patients (n=99) referred for evaluation of biochemical relapse of prostate cancer by [68Ga]THP-PSMA PET/CT were analyzed retrospectively. Patients underwent a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified cohorts of positive PET/CT results, standardized uptake values (SUVs) and target-to-background ratios (TBRs) were analyzed, and compared between standard and delayed imaging.Results: At least one lesion suggestive of recurrent or metastatic prostate cancer was identified on PET images in 52 patients (52.5%). Detection rates of [68Ga]THP-PSMA PET/CT increased with increasing PSA level: 94.1% for a PSA value of ≥10 ng/mL, 77.3% for a PSA value of 2 to <10 ng/mL, 54.5% for a PSA value of 1 to <2 ng/mL, 14.3% for a PSA value of 0.5 to <1 ng/mL, 20.0% for a PSA value of >0.2 to <0.5, and 22.2% for a PSA value of 0.01 to 0.2 ng/mL. [68Ga]THP-PSMA uptake (SUVs) in metastases decreased over time, whereas TBRs improved. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 2% of [68Ga]THP-PSMA PET/CT scans. Detection rate was higher in patients with a Gleason score ≥8 (P=0.02) and in patients receiving androgen deprivation therapy (P=0.003).Conclusions: In this study, [68Ga]THP-PSMA PET/CT showed suitable detection rates in patients with biochemical recurrence of prostate cancer and PSA levels ≥ 2 ng /mL. Detections rates were lower than in previous studies evaluating other PSMA ligands, though prospective direct radiotracer comparison studies are mandatory particularly in patients with low PSA levels to evaluate the relative performance of different PSMA ligands. [ABSTRACT FROM AUTHOR]

ᅟ: Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. F-FDG PET has been used, but may be complicated by physiological myocyte uptake. We evaluated the potential of two alternative imaging targets: lactoferrin binding by Ga-citrate and somatostatin receptor binding by Ga-DOTATATE. Methods: C57Bl/6 mice underwent permanent coronary artery ligation. Serial PET imaging was performed 3 - 7 days after MI using Ga-citrate, Ga-DOTATATE, or F-FDG with ketamine/xylazine suppression of myocyte glucose uptake. Myocardial perfusion was evaluated by N-ammonia PET and cardiac geometry by contrast-enhanced ECG-gated CT. Results: Mice exhibited a perfusion defect of 30 - 40 % (of the total left ventricle) with apical anterolateral wall akinesia and thinning on day 7 after MI. F-FDG with ketamine/xylazine suppression demonstrated distinct uptake in the infarct region, as well as in the border zone and remote myocardium. The myocardial standardized uptake value in MI mice was significantly higher than in healthy mice under ketamine/xylazine anaesthesia (1.9 ± 0.4 vs. 1.0 ± 0.1). Ga images exhibited high blood pool activity with no specific myocardial uptake up to 90 min after injection (tissue-to-blood contrast 0.9). Ga-DOTATATE was rapidly cleared from the blood, but myocardial SUV was very low (0.10 ± 0.03). Conclusion: Neither Ga nor Ga-DOTATATE is a useful alternative to F-FDG for PET imaging of myocardial inflammation after MI in mice. Among the three tested approaches, F-FDG with ketamine/xylazine suppression of cardiomyocyte uptake remains the most practical imaging marker of post-infarct inflammation. [ABSTRACT FROM AUTHOR]

Unlabelled: The aim of this study is to verify the in vivo stability, to determine the biodistribution and to estimate the unspecific radiotoxicity of an (211)At-labelled CD33-antibody ((211)At-antiCD33) in mice with a view to therapeutic application in treating leukaemia., Animals, Methods: (211)At was produced via the (209)Bi(a,2n)(211)At reaction and was linked via 3-(211)At-succinimidyl-benzoate to the antiCD33-antibody. The biodistribution and the in vivo stability in serum were determined after i.v.-injection in NMRI nu/nu-mice. For toxicity experiments, mice received either three times 315-650 kBq (211)At-antiCD33 or unlabelled antibody and NaCl-solution respectively., Results: (211)At-antiCD33 showed a characteristic biodistribution complying with the unspecific antibody retention in the reticular endothelial system. The largest proportion of radioactivity remained in blood and blood-rich tissues with a minor accumulation in the thyroid and stomach. After 21 h, >85% of activity in serum still represented intact antibody. Mice showed no difference in unspecific toxicity of (211)At-labelled antibodies over six months compared to those treated with unlabelled antibody and NaCl-solution respectively, with regard to histopathologic lesions, survival time, behaviour and haemograms., Conclusion: The radiolabelling method yielded adequate in vivo stability of (211)At-antiCD33. Biodistribution with rapid elimination of free (211)At via kidneys and urine complies with requirements for targeted therapy. Activity doses potentially required for treatment do not elicit radiotoxicity to normal organs in mice. Further development is required to enhance the apparent specific activity and to verify the efficacy in an adequate animal model before phase I clinical studies in leukaemia can be envisaged.

Purpose: The objective of this study was to determine and verify the stability of 211At-labelled antibodies under physiological conditions and their specific cell-binding capacity for selected epitopes, in order to evaluate the potential of 211At for alpha-radioimmunotherapy., Methods: 211At was produced at the department's cyclotron and was linked via the intermediate 3-211At-succinimidyl-benzoate (SAB) to the antineoplastic antibodies rituximab, gemtuzumab and gemtuzumab ozogamicin. The stability of the labelled antibodies was determined in serum for 21 h. Cell-binding experiments on HL-60 and CI-1 cells included kinetic, saturation and competitive binding studies. For comparison the binding to antigen-negative cells was determined. The binding specificity and affinity and the IC50-values were evaluated., Results: A consistent yield of 30% and a specific activity of 3 MBq/nmol was obtained. The stability of 211At-antibodies in murine serum exceeded 85% at 37 degrees C. Cell-binding to antigen-positive cells was >25%, while binding to antigen-negative cells did not exceed the unspecific binding and was smaller than 1%. IC50 values ranged between 2 and 11 nmol/L., Conclusions: A routine preparation of 211At-labelled antibodies was established and the stability of the 211At-labelled antibodies under physiologic conditions was verified. Apparently, labelling of antibodies with 211At by the method described does not compromise the affinity and specificity to the respective epitopes.