[en] The High Acceptance Recoil Polarimeter (HARP) is a new polarimeter detector which is based on the recoil principle, using liquid hydrogen as an analyser. With the analysing power, A_y well known for n-p and p-p scattering, the asymmetry from the incoming nucleon flux and the normal polarisation variable, P₀^y can be determined in a ²H(e, e'n-vector) reaction. The ²H(e, e'n-vector) experiment which was performed at NIKHEF, Amsterdam which utilised HARP as means to detect the polarisation of the neutron took place late in 1997. This thesis documents my involvement in the building and testing of this new detector system, my participation in the development of the data-acquisition software and in a commissioning experiment which took place at NIKHEF in November 1996 involving HARP. My work at ISN Grenoble on the analysis of the wire chamber information from the commissioning experiment is also documented. An overview of the HARP detector and its components are described and their performance under experimental conditions are documented. In addition, the experimental hall at NIKHEF, Emin, is also described. This thesis also describes the running of the ²H(e, e'n-vector) experiment, the set-up at the experimental hall at NIKHEF and the problems encountered during this experiment involving the failure of the electron beam and the wire chambers of the HARP detector. A novel analysis method to extract as much information as possible in the absence of wire chamber data and with the reduced beam time of the experiment is presented where a value of 0.03 for P₀^y is found. (author)

[en] Radiotheranostics with 177Lu-PSMA have changed the treatment paradigm in patients with prostate cancer, becoming the new standard in certain settings. Terbium-161 (161Tb) has been recently investigated as a potential radionuclide for radiotheranostics in various types of cancer, including metastatic castration-resistant prostate cancer (mCRPC). The nuclear medicine team at King Hussein Cancer Center (KHCC) in Amman, Jordan, recently published the first-in-human SPECT/CT imaging results following a well-tolerated dose of 161Tb-PSMA radioligand therapy with no treatment-related adverse events, adding to the potential of radiotheranostics in prostate ancer. Two clinical trials for 161Tb-PSMA radioligand therapy in prostate cancer are currently underway and will provide valuable insights. This review will shed light on the expanding field of radiotheranostics in prostate cancer, which is not without challenges, and will discuss how the introduction of a new therapeutic option like 161Tb-PSMA may help to combat these challenges and build on the proven success of 177Lu-PSMA based radiotheranostics for the benefit of prostate cancer patients worldwide

[en] Multidrug resistance (MDR) in tumors is associated with P-glycoprotein (Pgp) expression. In vivo quantitation of Pgp may allow MDR to be evaluated noninvasively prior to treatment planning. The purpose of this study was to radiolabel MRK-16, a monoclonal antibody that targets an external epitope of P-glycoprotein, and perform in vivo quantitation of P-glycoprotein in a MDR xenograft nude mouse model. MRK-16 was labeled with ¹²⁵I by the iodogen method, with subsequent purification by size exclusion chromatography. Groups of 10 Balb/c mice were each xenografted with colchicine-resistant or -sensitive neuroblastoma cell lines, respectively. Whole body clearance and tumor uptake over time was quantitated by gamma camera imaging, and biodistribution studies were performed with [¹²⁵]MRK-16 and an isotype matched control antibody, A33. Quantitative autoradiography and immunohistochemistry analysis of tumors was also evaluated to confirm specific targeting of [¹²⁵I]MRK-16. Peak tumor uptake was at 2-3 days post-injection, and was significantly greater in resistance compared to sensitive tumors (mean % injected dose/g ± SD) (18.76 ± 2.94 vs 10.93 ± 0.96; p < 0.05). Quantitative autoradiography verified these findings (19.13 ± 0.622 vs 12.08 ± 0.38, p < 0.05). Specific binding of [¹²⁵I]MRK-16 was confirmed by comparison to [¹³¹I]A33 in biodistribution studies, and localized to cellular components of tissue stroma by comparison of histologic and autoradiographic sections of sensitive and resistant tumors. Immunoblot analysis demonstrated a 4.5-fold difference in P-glycoprotein expression between sensitive and resistant cell lines without colchicine selective pressure. We conclude that in vivo quantitation of P-glycoprotein in MDR tumors can be performed with [¹²⁵I]MRK-16. These findings suggest a potential clinical application for radiolabeled MRK-16 in the in vivo evaluation of multidrug resistance in tumors

[en] We have demonstrated that FMISO uptake is significantly higher in tumor tissue in the C6 intracerebral glioma rat model compared to normal brain, and that there is persisting hypoxia in gliomas independent of tumor size. FMISO uptake was observed homogeneously throughout viable glioma tissue in tumor sizes ranging from 2mm to almost 1cm. Quantitation of uptake of FMISO showed a tumor/brain ratio of 1.9 and a tumor/blood ratio of 2.6 at 2 hours post injection

[en] Preclinical evaluation of the therapeutic potential of radiolabeled antibodies is commonly performed in a xenografted nude mouse model. To assess therapeutic efficacy it is important to estimate the absorbed dose to the tumor and normal tissues of the nude mouse. The current study was designed to accurately measure radiation does to human neuroblastoma xenografts and normal organs in nude mice treated with I-131-labeled 3F8 monoclonal antibody (MoAb) against disialoganglioside GD₂ antigen. Absorbed dose estimates were obtained using two different approaches: (1) measurement with teflon-imbedded CaSO₄:Dy mini-thermoluminescent dosimeters (TLDs) and (2) calculation using mouse S-factors. The calculated total dose to tumor one week after i.v. injection of the 50 μCi I-131-3F8 MoAb was 604 cGy. The corresponding decay corrected and not corrected TLD measurements were 109 ± 9 and 48.7 ± 3.4 cGy respectively. The calculated to TLD-derived dose ratios for tumor ranged from 6.1 at 24 h to 5.5 at 1 week. The light output fading rate was found to depend upon the tissue type within which the TLDs were implanted. The decay rate in humor, muscle, subcutaneous tissue and in vitro, were 9.5, 5.0, 3.7 and 0.67% per day, respectively. We have demonstrated that the type of tissue in which the TLD was implanted strongly influenced the in vivo decay of light output. Even with decay correction, a significant discrepancy was observed between MIRD-based calculated and CaSO₄:Dy mini-TLD measured absorbed doses. Batch dependence, pH of the tumor or other variables associated with TLDs which are not as yet well known may account for this discrepancy

[en] ⁶⁸Ga-DOTATATE positron emission tomography (PET) is a molecular imaging technology which has shown superiority over ¹¹¹In-octreotide scanning for the detection and staging of neuroendocrine tumors. We report three patients with pancreatic masses that were ultimately diagnosed as clear cell renal cell carcinoma (ccRCC) metastases on histopathology. During their initial diagnostic assessment, the three patients underwent both ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and ⁶⁸Ga-DOTATATE PET. While all three patients' lesions showed variable ¹⁸F-FDG avidity, uptake on ⁶⁸Ga-DOTATATE PET was comparatively intense. The small case series illustrates the need to consider ccRCC in the differential diagnosis of ⁶⁸Ga-DOTATATE avid lesions. (author)

[en] We aimed to characterize the binding properties of an ¹⁸ F-estradiol positron emission tomography (PET) tracer in its ability to bind to the α and β forms of estrogen receptors in vitro and confirmed its binding to estrogen receptor α in vivo. ¹⁸ F-estradiol PET tracer binds in vitro with high specificity to the estrogen receptor α isoform, with minimal binding to estrogen receptor β. This may help distinguish human cancers with biological dependence on estrogen receptor subtypes

[en] The management of malignant pleural mesothelioma represents one of the most challenging issues in oncology, as there is no proven long-term benefit from surgery, radiotherapy or chemotherapy alone or in combination. Locoregional progression remains the major cause of death, but radical surgical resection may produce major postoperative morbidity. While radical or postoperative radiotherapy using conventional techniques has resulted in severe toxicity with no impact on survival, recent advances in radiotherapy delivery may be more effective. We treated patients with locally advanced mesothelioma whose tumours had been sub optimally resected with high-dose three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) to large volumes of one hemithorax, using CT and positron emission tomography (PET) scan-based treatment planning. Clinical outcomes were assessed by determining patterns of failure and metabolic changes in total glycolytic volume (TGV) between pre- and post-irradiation ¹⁸F-FDG PET/CT scans and by recording acute and late toxicity grades. Fourteen patients were analysed with 40 PET scans performed before and up to 4.5 years after radiotherapy. Eleven patients had pleurectomy/decortications, one had an extrapleural pneumonectomy and two had no surgery. Four patients who received chemotherapy had all progressed prior to radiotherapy. After radiotherapy, the in-field local control rate was 71%. No progression occurred in two patients, one was salvaged with further radiotherapy to a new site, four recurred inside the irradiated volume all with concurrent distant metastases and the other seven had distant metastases only. The TGVs were reduced by an average of 67% (range 12–100%) after doses of 45 to 60 Gy to part or all of one hemithorax. There were no serious treatment-related toxicities. Median survival was 25 months from diagnosis and 17 months after starting radiotherapy. We have established that mesothelioma can be locally controlled with high radiation doses using 3DCRT or IMRT, and that strict normal tissue dose constraints have limited radiation toxicities. Radiotherapy should be considered to prevent or delay the local manifestations of progressive disease in suitable patients after surgery including extrapleural pneumonectomy and pleurectomy/decortication. Higher radiation doses may allow more effective palliation.

[en] Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans Copyright (2004) Blackwell Publishing Asia Pty Ltd

[en] ^99mTc-DI-DD-3B6/22-80B3 (Thromboview, hereafter abbreviated to ^99mTc-DI-80B3 Fab') is a humanised, radiolabelled monoclonal antibody Fab' fragment with high affinity and specificity for the D-dimer domain of cross-linked fibrin. The purpose of this study was to evaluate the safety, pharmacokinetics and dosimetry of four increasing doses of ^99mTc-DI-80B3 Fab' in healthy volunteers. Thirty-two healthy volunteers (18-70 years; 16 male, 16 female) received a single intravenous injection of 0.5, 1.0, 2.0 or 4.0 mg of ^99mTc-DI-80B3 Fab'. Safety outcomes (vital signs, electrocardiography, haematology, biochemistry, adverse events and development of human anti-human antibodies) were assessed up to 30 days post injection. Blood and urine samples were collected up to 48 h post injection. Gamma camera images were acquired at 0.5, 1, 2, 4, 6 and 24 h post injection. Dosimetry was performed using standard MIRD methodology. No adverse events considered to be drug related were observed. Human anti-human antibody was not detectable in any subject during the follow-up period. ^99mTc-DI-80B3 Fab' had a rapid initial plasma clearance (t_1/2α=1 h). The pharmacokinetic profile of the Fab' fragment was generally linear across the four dose cohorts. By 24 h, 30-35% of the administered radioactivity appeared in the urine. There was marked renal accumulation with time, but no specific uptake was identified within other normal tissues. The effective dose was 9 mSv/750 MBq. (orig.)