Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent β--emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate

In recent years, implementation of 68Ga-radiometalated peptides for PET imaging of cancer has attracted the attention of clinicians. Herein, we propose the use of 44Sc (half-life = 3.97 h, average β+ energy [Eβ+av] = 632 keV) as a valuable alternative to 68Ga (half-life = 68 min, Eβ+av = 830 keV) for imaging and dosimetry before 177Lu-based radionuclide therapy. The aim of the study was the preclinical evaluation of a folate conjugate labeled with cyclotron-produced 44Sc and its in vitro and in vivo comparison with the 177Lu-labeled pendant. Methods: 44Sc was produced via the 44Ca(p,n)44Sc nuclear reaction at a cyclotron (17.6 ± 1.8 MeV, 50 μA, 30 min) using an enriched 44Ca target (10 mg 44CaCO3, 97.00%). Separation from the target material was performed by a semiautomated process using extraction chromatography and cation exchange chromatography. Radiolabeling of a DOTA-folate conjugate (cm09) was performed at 95°C within 10 min. The stability of 44Sc-cm09 was tested in human plasma. 44Sc-cm09 was investigated in vitro using folate receptor–positive KB tumor cells and in vivo by PET/CT imaging of tumor-bearing mice Results: Under the given irradiation conditions, 44Sc was obtained in a maximum yield of 350 MBq at high radionuclide purity (>99%). Semiautomated isolation of 44Sc from 44Ca targets allowed formulation of up to 300 MBq of 44Sc in a volume of 200–400 μL of ammonium acetate/HCl solution (1 M, pH 3.5–4.0) within 10 min. Radiolabeling of cm09 was achieved with a radiochemical yield of greater than 96% at a specific activity of 5.2 MBq/nmol. In vitro, 44Sc-cm09 was stable in human plasma over the whole time of investigation and showed folate receptor–specific binding to KB tumor cells. PET/CT images of mice injected with 44Sc-cm09 allowed excellent visualization of tumor xenografts. Comparison of cm09 labeled with 44Sc and 177Lu revealed almost identical pharmacokinetics. Conclusion: This study presents a high-yield production and efficient separation method of 44Sc at a quality suitable for radiolabeling of DOTA-functionalized biomolecules. An in vivo proof-of-concept study using a DOTA-folate conjugate demonstrated the excellent features of 44Sc for PET imaging. Thus, 44Sc is a valid alternative to 68Ga for imaging and dosimetry before 177Lu-radionuclide tumor therapy.

Validity of the Adult ADHD Self-Report Scale (ASRS) as a screener for adult ADHD in treatment seeking substance use disorder patients

Background: To detect attention deficit hyperactivity disorder (ADHD) in treatment seeking substance use disorders (SUD) patients, a valid screening instrument is needed. Objectives: To test the performance of the Adult ADHD Self-Report Scale V 1.1(ASRS) for adult ADHD in an international sample of treatment seeking SUD patients for DSM-IV-TR; for the proposed DSM-5 criteria; in different subpopulations, at intake and 1–2 weeks after intake; using different scoring algorithms; and different externalizing disorders as external criterion (including adult ADHD, bipolar disorder, antisocial and borderline personality disorder). Methods: In 1138 treatment seeking SUD subjects, ASRS performance was determined using diagnoses based on Conner's Adult ADHD Diagnostic Interview for DSM-IV (CAADID) as gold standard. Results: The prevalence of adult ADHD was 13.0% (95% CI: 11.0–15.0%). The overall positive predictive value (PPV) of the ASRS was 0.26 (95% CI: 0.22–0.30), the negative predictive value (NPV) was 0.97 (95% CI: 0.96–0.98). The sensitivity (0.84, 95% CI: 0.76–0.88) and specificity (0.66, 95% CI: 0.63–0.69) measured at admission were similar to the sensitivity (0.88, 95% CI: 0.83–0.93) and specificity (0.67, 95% CI: 0.64–0.70) measured 2 weeks after admission. Sensitivity was similar, but specificity was significantly better in patients with alcohol compared to (illicit) drugs as the primary substance of abuse (0.76 vs. 0.56). ASRS was not a good screener for externalizing disorders other than ADHD. Conclusions: The ASRS is a sensitive screener for identifying possible ADHD cases with very few missed cases among those screening negative in this population.

Zur Beschwerde des Brandgeschädigten Ulrich Kipfer

Kommentar zu einem Zeitungsartikel von Albert Bitzius, erschienen im "Intelligenzblatt für die Stadt Bern" vom 14. Februar 1849