Combined Early and Late [68Ga]PSMA-HBED-CC PET Scans Improve Lesion Detectability in Biochemical Recurrence of Prostate Cancer with Low PSA Levels.

PURPOSE: Our aim was to evaluate the benefit of early (1 h post-injection (p.i.)) and late (3 h p.i.) [68Ga]PSMA-HBED-CC positron emission tomography (PET)/x-ray computed tomography (CT) imaging for detection of biochemical recurrence (BCR) of prostate cancer (PCa). PROCEDURES: Seventy patients with BCR of the PCa and prostate-specific antigen (PSA) levels of less than 2.0 µg/l were subjected to [68Ga]PSMA-HBED-CC PET (mean injected activity 180 MBq). While early imaging contained whole body scans, late imaging was confined to the pelvis and the lower abdomen. Uptake in suspicious lesions was analyzed by peak and maximum standardized uptake values (SUVpeak/max). Tumor-to-background ratios were calculated for all lesions in which the liver served as reference organ. The Wilcoxon matched-pair signed-rank test was used to compare the uptake in suspicious lesions between early and late imaging. Follow-up data were used to validate the existence of the additionally detected lesions. RESULTS: Forty-four of the 70 patients thus examined were interpreted as PSMA-positive in early and/or late scans while 26 remained without suspicion of PSMA tracer uptake. A total of 70 suspicious lesions were analyzed. Ten tumor-suspicious lesions from seven different patients were better or exclusively visible in the late measurements while three tumor-suspicious lesions from three different patients were better or exclusively visible in the early images. A validation by follow-up data was possible for 11 of these 13 additionally detected lesions. In direct comparison between early and late imaging, the mean SUVmax in PSMA-positive lesions was 74 % higher (p < 0.001) and the mean SUVpeak was 36 % higher (p = 0.001) in the late scans. The SUVmean in the reference regions was decreasing in the late measurements, whereas the mean TBR increased by a factor of 3 (p < 0.001). Taking confirmed lesions only into account, we estimated a 10 % gain in additionally detected PSMA-positive lesions (7/70) within the patient cohort. CONCLUSIONS: The time period between injection and data acquisition influences the detection rate of [68Ga]PSMA-HBED-CC PET/CT. In biochemical recurrence with low PSA levels, late [68Ga]PSMA-HBED-CC PET/CT imaging offers frequent advantages with regard to lesion contrast.

GNA11 and N-RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system.

AIM: Primary melanocytic tumours are uncommon neoplasms of the central nervous system. Although similarities with uveal melanomas have been hypothesized, data on their molecular features are limited. METHODS: In this study, we investigated the mutational status of BRAF(V600E) , KIT, GNAQ, GNA11, N-RAS and H-RAS in a series of 19 primary melanocytic tumours of the central nervous system (CNS). RESULTS: We identified six cases harbouring mutations in the hotspot codon 209 of the GNAQ gene and two cases with mutations in the hotspot codon 209 of the GNA11 gene. Two mutations in codon 61 of N-RAS were also found. In the single strand conformation polymorphism (SSCP) analysis, no shifts corresponding to BRAF(V600E) mutations or suggesting activating mutations in the KIT gene were observed. CONCLUSIONS: In primary melanocytic tumours of the CNS, GNA11 and N-RAS mutations represent a mechanism of MAPK pathway activation alternative to the common GNAQ mutations. On the other hand, BRAF(V600E) mutations and activating KIT mutations seem to be absent or very rare in these tumours.

[Radiation exposure in the environment of patients after application of radiopharmaceuticals. Part 2: Therapeutic procedures]. / Strahlenexposition in der Umgebung von Patienten nach Radiopharmaka-Applikation. Teil 2: Nuklearmedizinische Therapien.

AIM: After therapeutical application of radionuclides the patient has to be regarded as a radioactive source. The radiation exposure differs from diagnostic nuclear medicine due to the amount of radioactivity and due to beta-radiation. Measurements of photon dose rates were carried out and estimates of beta-radiation outside the patient using Monte-Carlo methods. Calculations of maximum beta-ranges in tissue were also performed. Detailed knowledge of the radiation exposure close to the patient is of major importance with respect to radiation protection of the staff. METHOD: Photon dose rates for 32 patients were determined after treatment with [131I]NaI and [131I]meta-iodobenzylguanidin, [32P]Na2HPO4, [90Y]Zevalin and [153Sm]EDTMP. Readings were taken immediately after application at eight distances. RESULTS: For therapies with 131I photon dose rates amount to 2 mSv.h(-1).GBq(-1) close to the patient. Taking the typical activities of 3.7 GBq for thyroid carcinoma and up to 11 GBq for mIBG therapies into account this leads to a considerable radiation exposure of approximately 7.5 mSv/h and 20 mSv/h, respectively. At a distance of 2 m the dose rates fall to 1/100 compared to the vicinity. For 153Sm the maximum of 100 microSv.h(-1).GBq(-1) is significantly lower compared to therapies using radioiodine. After application of 32P or 90Y all photon dose rates are lower (<10 microSv.h(-1).GBq(-1)) but in both cases high energy beta-particles associated with high maximum ranges exceeding 1 cm in tissue have to be considered. CONCLUSION: The remarkable difference of the dose rates in the vicinity of the radioactive patient compared to readings at 2 m distance underlines the major importance of the distance for radiation protection. After application of nuclides emitting high energy beta-particles their contribution outside the patient should be considered. For typical procedures in the patient's vicinity the radiation exposure of the personnel remains below the annual limit of 20 mSv.

Precursors of symbol formation and childhood autism.

The salience of various precursory requirements for the formation of symbols is discussed. The conclusion is drawn that several necessary precursors could be assumed, and two experiments are described that were designed to test for the presence of these precursors in autistic children compared to matched retarded children. First, there was a study of the children's ability to imitate and form internal images, and then there was a study of their development of a concept of object permanence and ability to anticipate. These studies led to the conclusion that the autistic children could form internal images but seemed to lack the ability to manipulate them in a purposeful and meaningful manner, as reflected in their inability to show symbolic imitations and their lack of tendency to use elements of their perceptions that might allow prediction of future events. The findings are discussed in terms of cognitive and social development.