Increased target volume and hydrogen content in [11C]CH4 production

Introduction High starting radioactivity is usually advantageous for producing radiopharmaceuticals with high specific radioactivity. However, the [11C]CH4 yields from N2-H2 gas target fall short from theoretical amounts, as calculated from the cross section for the well-known 14N(p,α)11C nuclear reaction1. The beneficial effect of increased target chamber temperature on [11C]CH4 yields has recently been brought forward by us2 and others3. In addition to the temperature effect, our attention has also been on the hydrogen content factor. This study intends to examine the N2-H2 target performance in a substantially larger target chamber and at higher temperatures than our setup before and compare the results to the existing data. Materials and Methods Aluminium bodied custom design target chamber is used in fixed 17 MeV proton beam irradiations. Target chamber is equipped with heating elements and cooling circuit for temperature control. In addition to the target chamber body temperature, the target gas loading pressure and irradiation current can be varied. The irradiation product is collected into an ad-sorbent trap that was immersed in a liquid argon cooling bath within a dose calibrator. Results and Conclusion Pursued data will show [11C]CH4 saturation yields (Ysat [GBq/µA]) at different irradiation and target parameters

Flare on [18F]PSMA-1007 PET/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: possible marker of tumor aggressiveness in treatment-naïve metastatic prostate cancer patients

Purpose Short-term androgen deprivation therapy (ADT) is known to increase heterogeneously prostate-specific membrane antigen (PSMA) expression. This phenomenon might indicate the potential of cancer lesions to respond to ADT. In this prospective study, we evaluated the flare on [F-18]PSMA-1007 PET/CT after ADT in metastatic prostate cancer (PCa). Given that aggressive PCa tends to display FDG uptake, we particularly investigated whether the changes in PSMA uptake might correlate with glucose metabolism.Methods Twenty-five men with newly diagnosed treatment-naive metastatic PCa were enrolled in this prospective registered clinical trial. All the patients underwent [F-18]PSMA-1007 PET/CT immediately before and 3-4 weeks after ADT initiation (degarelix). Before ADT, [F-18]FDG PET/CT was also performed. Standardized uptake values (SUV)max of primary and metastatic lesions were calculated in all PET scans. Serum PSA and testosterone blood samples were collected before the two PSMA PET scans. The changes in PSMA uptake after ADT were represented as Delta SUVmax.Results All the patients reached castration levels of testosterone at the time of the second [F-18]PSMA-1007 PET/CT. Overall, 57 prostate, 314 lymph nodes (LN), and 406 bone lesions were analyzed. After ADT, 104 (26%) bone, 33 (11%) LN, and 6 (11%) prostate lesions showed an increase (>= 20%) in PSMA uptake, with a median Delta SUVmax of + 50%, + 60%, and + 45%, respectively. Among the lesions detected at the baseline [F-18]PSMA-1007 PET/CT, 63% bone and 46% LN were FDG-positive. In these metastases, a negative correlation was observed between the PSMA Delta SUVmax and FDG SUVmax (p Conclusions A heterogeneous increase in PSMA uptake after ADT was detected, most evidently in bone metastases. We observed a negative correlation between the PSMA flare and the intensity of glucose uptake as well as the decrease of serum PSA, suggesting that lesions presenting with such flare might potentially be less aggressive.</p

Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with Cu-64 Using NOTA and NODAGA

Imaging using affi body molecules enables discrimination between breast cancer metastases with high and low expression of HER2, making appropriate therapy selection possible. This study aimed to evaluate if the longer half-life of Cu-64 (T-1/2 = 12.7h) would make Cu-64 a superior nuclide compared to Ga-68 for PET imaging of HER2 expression using affibody molecules. The synthetic ZHER2: S1 affibody molecule was conjugated with the chelators NOTA or NODAGA and labeled with Cu-64. The tumor-targeting properties of Cu-64-NOTA-ZHER2: S1 and Cu-64-NODAGA-ZHER2: S1 were evaluated and compared with the targeting properties of Ga-68-NODAGA-ZHER2: S1 in mice. Both 64 Cu-NOTA-ZHER2: S1 and Cu-64-NODAGA-ZHER2: S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of Cu-64-NOTA-ZHER2: S1, Cu-64-NODAGA-ZHER2: S1, and Ga-68-NODAGAZHER2: S1, tumor uptakes did not differ significantly. Renal uptake of Cu-64-labeled conjugateswas dramatically reduced at 6 and 24 h after injection. Notably, radioactivity uptake concomitantly increased in blood, lung, liver, spleen, and intestines, which resulted in decreased tumor-to-organ ratios compared to 2 h postinjection. Organ uptake was lower for Cu-64-NODAGA-ZHER2: S1. The most probable explanation for this biodistribution pattern was the release and redistribution of renal radiometabolites. In conclusion, monoamide derivatives of NOTA and NODAGA may be suboptimal chelators for radiocopper labeling of anti-HER2 affibody molecules and, possibly, other scaffold proteins with high renal uptake

Evaluation of [F-18]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain

Purpose Recent studies have linked activated spinal glia to neuropathic pain. Here, using a positron emission tomography (PET) scanner with high spatial resolution and sensitivity, we evaluated the feasibility and sensitivity of N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin3-yl)acetamide -([F-18]F-DPA) imaging for detecting spinal cord microglial activation after partial sciatic nerve ligation (PSNL) in rats.Procedures Neuropathic pain was induced in rats (n = 20) by PSNL, and pain sensation tests were conducted before surgery and 3 and 7 days post- injury. On day 7, in vivo PET imaging and ex vivo autoradiography were performed using -[F-18]F-DPA or -[C-11]PK11195. Ex vivo biodistribution and PET imaging of the removed spinal cord were carried out with -[F-18]F-DPA. Sham-operated and PK11195pretreated animals were also examined.Results Mechanical allodynia was confirmed in the PSNL rats from day 3 through day 7. Ex vivo autoradiography showed a higher lesion-to-background uptake with -[F-18]F-DPA compared with -[C-11]PK11195. Ex vivo PET imaging of the removed spinal cord showed -[F-18]F-DPA accumulation in the inflammation site, which was immunohistochemically confirmed to coincide with microglia activation. Pretreatment with PK11195 eliminated the uptake. The SUV values of in vivo -[F-18]F-DPA and -[C-11]PK11195 PET were not significantly increased in the lesion compared with the reference region, and were fivefold higher than the values obtained from the ex vivo data. Ex vivo biodistribution revealed a twofold higher -[F-18] F-DPA uptake in the vertebral body compared to that seen in the bone from the skull.Conclusions[F-18]F-DPA aided visualization of the spinal cord inflammation site in PSNL rats on ex vivo autoradiography and was superior to -[C-11]PK11195. In vivo -[F-18]F-DPA PET did not allow for visualization of tracer accumulation even using a high-spatial-resolution PET scanner. The main reason for this result was due to insufficient SUVs in the spinal cord region as compared with the background noise, in addition to a spillover from the vertebral body.</p

Comparison of high and low molar activity TSPO tracer [18F]F-DPA in a mouse model of Alzheimer’s disease

[18F]F-DPA, a novel translocator protein 18 kDa (TSPO)-specific radioligand for imaging neuroinflammation, has to date been synthesized with low to moderate molar activities (Am’s). In certain cases, low Am can skew the estimation of specific binding. The high proportion of the non-radioactive component can reduce the apparent-specific binding by competitively binding to receptors. We developed a nucleophilic synthesis of [18F]F-DPA resulting in high Am (990 ± 150 GBq/µmol) and performed in vivo comparison with low Am (9.0 ± 2.9 GBq/µmol) [18F]F-DPA in the same APP/PS1-21 and wild-type mice (injected masses: 0.34 ± 0.13 µg/kg and 38 ± 15 µg/kg, respectively). The high level of microgliosis in the APP/PS1-21 mouse model enables good differentiation between diseased and healthy animals and serves better to distinguish the effect of differing Am on specific binding. The differing injected masses affect the washout profile and shape of the time–activity curves. Ratios of standardized uptake values obtained with high and low Am [18F]F-DPA demonstrate that there is a 1.5-fold higher uptake of radioactivity in the brains of APP/PS1-21 animals when imaging is carried out with high Am [18F]F-DPA. The differences between APP/PS1-21 and wild-type animals showed higher significance when high Am was used.</p

Molecular design of radiocopper-labelled Affibody molecules

The use of long-lived positron emitters Cu-64 or Cu-61 for labelling of Affibody molecules may improve breast cancer patients' stratification for HER-targeted therapy. Previous animal studies have shown that the use of triaza chelators for Cu-64 labelling of synthetic Affibody molecules is suboptimal. In this study, we tested a hypothesis that the use of cross-bridged chelator, CB-TE2A, in combination with Gly-Glu-Glu-Glu spacer for labelling of Affibody molecules with radiocopper would improve imaging contrast. CB-TE2A was coupled to the N-terminus of synthetic Affibody molecules extended either with a glycine (designation CB-TE2A-G-ZHER2:342) or Gly-Glu-Glu-Glu spacer (CB-TE2A-GEEE-ZHER2:342). Biodistribution and targeting properties of Cu-64-CB-TE2A-G-ZHER2:342 and Cu-64-CB-TE2A-GEEE-ZHER2:342 were compared in tumor-bearing mice with the properties of Cu-64-NODAGA-ZHER2:S1, which had the best targeting properties in the previous study. Cu-64-CB-TE2A-GEEE-ZHER2:342 provided appreciably lower uptake in normal tissues and higher tumor-to-organ ratios than Cu-64-CB-TE2A-GZHER2:342 and Cu-64-NODAGA-ZHER2:S1. The most pronounced was a several-fold difference in the hepatic uptake. At the optimal time point, 6 h after injection, the tumor uptake of Cu-64-CB-TE2A-GEEE-ZHER2: 342 was 16 +/- 6% ID/g and tumor-to-blood ratio was 181 +/- 52. In conclusion, a combination of the cross-bridged CB-TE2A chelator and Gly-Glu-Glu-Glu spacer is preferable for radiocopper labelling of Affibody molecules and, possibly, other scaffold proteins having high renal re-absorption

Evaluation of [F-18]F-DPA as a target for TSPO in head and neck cancer under normal conditions and after radiotherapy

Background Many malignant tumours have increased TSPO expression, which has been related to a poor prognosis. TSPO-PET tracers have not comprehensively been evaluated in peripherally located tumours. This study aimed to evaluate whether N,N-diethyl-2-(2-(4-([F-18]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ([F-18]F-DPA) can reflect radiotherapy (RT)-induced changes in TSPO activity in head and neck squamous cell carcinoma (HNSCC). Methods RT was used to induce inflammatory responses in HNSCC xenografts and cells. [F-18]F-DPA uptake was measured in vivo in non-irradiated and irradiated tumours, followed by ex vivo biodistribution, autoradiography, and radiometabolite analysis. In vitro studies were performed in parental and TSPO-silenced (TSPO siRNA) cells. TSPO protein and mRNA expression, as well as tumour-associated macrophages (TAMs), were also assessed. Results In vivo imaging and ex vivo measurement revealed significantly higher [F-18]F-DPA uptake in irradiated, compared to non-irradiated tumours. In vitro labelling studies with cells confirmed this finding, whereas no effect of RT on [F-18]F-DPA uptake was detected in TSPO siRNA cells. Radiometabolite analysis showed that the amount of unchanged [F-18]F-DPA in tumours was 95%, also after irradiation. PK11195 pre-treatment reduced the tumour-to-blood ratio of [F-18]F-DPA by 73% in xenografts and by 88% in cells. TSPO protein and mRNA levels increased after RT, but were highly variable. The proportion of M1/M2 TAMs decreased after RT, whereas the proportion of monocytes and migratory monocytes/macrophages increased. Conclusions [F-18]F-DPA can detect changes in TSPO expression levels after RT in HNSCC, which does not seem to reflect inflammation. Further studies are however needed to clarify the physiological mechanisms regulated by TSPO after RT

Quantitative elemental analysis of dry-ashed bark and wood samples of birch, spruce and pine from south-western Finland using PIXE

A total of over 200 different samples of bark and wood of Silver birch, Norway spruce and Scots pine were analysed. Samples were taken from several areas in western Finland, some with known sources of atmospheric heavy metal emission (Harjavalta, Ykspihlaja). Also analytical data for pine needles from some sites are reported. The chemical analyses were performed by thick-target particle-induced X-ray emission (PIXE) spectrometry after preconcentration by dry ashing of samples at 550oC. The following elements were quantified in most of the samples: P, S, K, Ca, Mn, Fe, Ni, Cu, Zn, Rb, Sr, Cd, Ba and Pb. The ash percentage and the chemical composition of ashes of different wood materials were also obtained, as dry ashing was used in the analytical procedure. The variations in elemental concentrations in wood and bark of an individual tree, expressed as RSDs, were mostly in the range 10 – 20 %. For several trees of the same species sampled from small areas (< 1 ha), the variations in elemental concentrations were surprisingly high (RSDs 20 – 50 %). In the vicinity of metal plants, effects of strong atmospheric heavy metal pollution (pollution factor above 100) were observed in pine bark. The increase of heavy metal content in wood samples from the same sites was quite small. Elemental concentrations in ashes of bark and wood, from areas with no local source of atmospheric pollution, were relatively uniform. Based on this observation an alternative way of demonstrating atmospheric pollution of tree bark is discussed