Økonomiske sanktioner som politisk værktøj

John J. Forrer ser nærmere på økonomiske sanktioner, som er blevet et af den amerikanske regerings foretrukne politiske værktøjer.&nbsp

Wavelength-dependent effect of tetra(m-hydroxyphenyl)chlorin for photodynamic therapy in an ‘early' squamous cell carcinoma model

The purpose of the present study was to correlate the wavelength of the irradiation source with the phototoxic activity of tetra(m-hydroxyphenyl)chlorin (mTHPC) in healthy and neoplastic mucosae. The hamster tumour model for early squamous cell carcinoma was used in these experiments. In vitro and in vivo studies have shown that mTHPC absorbs significantly at 652 nm (1, 2). This wavelength is used currently in clinical mTHPC photodynamic therapy (PDT) trials. In order to study the wavelength dependence of the phototoxic effect on normal and tumour tissues, irradiation tests were performed 4 days after injection of 0.5mg kg-1 mTHPC. An argon-ion pumped dye laser was used as the light source. The light dose of 12 J cm-2 was delivered at a light dose rate of 150 mW cm-2. The wavelength was varied between 642.5 and 665 nm at 2.5-nm increments. The PDT damage was evaluated in serial Haematoxylin and Eosin stained sections using a tissue-damage scale. Light between 647.5 and 652.5 nm induced the highest damage to both the healthy and tumour mucosae. At wavelengths equal to or below 645 nm, and equal to or above 655 nm, tissue damage decreased. Wavelengths below 642 nm and above 660 nm did not induce any visible tissue damage. These results suggest that the in vivo optimal wavelength range for PDT with mTHPC is between 647 and 652 nm. This information is essential for selecting an appropriate light sourc

A comparison of 111In-DOTATOC and 111In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours

[Yttrium-90-DOTA-Tyr3]-octreotide (DOTATOC) and [177Lu-DOTA-Tyr3-Thr8]-octreotide (DOTATATE) are used for peptide receptor-mediated radionuclide therapy (PRMRT) in neuroendocrine tumours. No human data comparing these two compounds are available so far. We used 111In as a surrogate for 90Y and 177Lu and examined whether one of the 111In-labelled peptides had a more favourable biodistribution in patients with neuroendocrine tumours. Special emphasis was given to kidney uptake and tumour-to-kidney ratio since kidney toxicity is usually the dose-limiting factor. Five patients with metastatic neuroendocrine tumours were injected with 222MBq 111In-DOTATOC and 111In-DOTATATE within 2 weeks. Up to 48h after injection, whole-body scans were performed and blood and urine samples were collected. The mean absorbed dose was calculated for tumours, kidney, liver, spleen and bone marrow. In all cases 111In-DOTATATE showed a higher uptake (%IA) in kidney and liver. The amount of 111In-DOTATOC excreted into the urine was significantly higher than for 111In-DOTATATE. The mean absorbed dose to the red marrow was nearly identical. 111In-DOTATOC showed a higher tumour-to-kidney absorbed dose ratio in seven of nine evaluated tumours. The variability of the tumour-to-kidney ratio was high and the significance level in favour of 111In-DOTATOC was P=0.065. In five patients the pharmacokinetics of 111In-DOTATOC and 111In-DOTATATE was found to be comparable. The two peptides appear to be nearly equivalent for PRMRT in neuroendocrine tumours, with minor advantages for 111In/90Y-DOTATOC; on this basis, we shall continue to use 90Y-DOTATOC for PRMRT in patients with metastatic neuroendocrine tumour

Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial

Purpose: Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting 90Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5mm of 90Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide 213Bi with a mean tissue range of 81µm may have a more favourable toxicity profile. Therefore, we evaluated locally injected 213Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality. Methods: In a pilot study, we included five patients with critically located gliomas (WHO grades II-IV). After diagnosis by biopsy, 213Bi-DOTA-substance P was locally injected, followed by serial SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the functional outcome was evaluated. Results: Targeted radiopeptide therapy using 213Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. 213Bi-DOTA-substance P showed high retention at the target site. MR imaging was suggestive of radiation-induced necrosis and demarcation of the tumours, which was validated by subsequent resection. Conclusion: This study provides proof of concept that targeted local radiotherapy using 213Bi-DOTA-substance P is feasible and may represent an innovative and effective treatment for critically located gliomas. Primarily non-operable gliomas may become resectable with this treatment, thereby possibly improving the prognosi

Clinical assessment of fluorescence cystoscopy during transurethral bladder resection in superficial bladder cancer

The prognosis of superficial bladder cancer in terms of recurrence and disease progression is related to bladder tumor multiplicity and the presence of concomitant "plane” tumors such as high-grade dysplasia and carcinoma in situ. This study in 33 patients aimed to demonstrate the role of fluorescence cystoscopy in transurethral resection of superficial bladder cancer. The method is based on the detection of protoporphyrin-IX-induced fluorescence in urothelial cancer cells by topical administration of 5-aminolevulinic acid. The sensitivity and the specificity of this procedure on apparently normal mucosa in superficial bladder cancer are estimated to be 82.9% and 81.3%, respectively. Thus, fluorescence cytoscopy is a simple and reliable method for mapping the bladder mucosa, especially in the case of multifocal bladder disease, and it facilitates the screening of occult dysplasi

Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called "remainder of the body" to the bone marrow

Lutetium-labelled peptides for therapy of neuroendocrine tumours

Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with 177Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with 177Lu-[DOTA0,Tyr3]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with 177Lu-DOTATATE as well as the limited side effects with additional cycles of 177Lu-DOTATATE suggest that more cycles of 177Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of 90Y-[DOTA0,Tyr3]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with 177Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with 177Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours

Wavelength-dependent effect of tetra(m-hydroxyphenyl) chlorin for photodynamic therapy in an "early" squamous cell carcinoma model

The purpose of the present study was to correlate the wavelength of the irradiation source with the phototoxic activity of tetra(m-hydroxyphenyl)chlorin (mTHPC) in healthy and neoplastic mucosae. The hamster tumour model for early squamous cell carcinoma was used in these experiments. In vitro and in vivo studies have shown that mTHPC absorbs significantly at 652 nm (1, 2). This wavelength is used currently in clinical mTHPC photodynamic therapy (PDT) trials. In order to study the wavelength dependence of the phototoxic effect on normal and tumour tissues, irradiation tests were performed 4 days after injection of 0.5mg kg-1 mTHPC. An argon-ion pumped dye laser was used as the light source. The light dose of 12 J cm-2 was delivered at a light dose rate of 150 mW cm-2. The wavelength was varied between 642.5 and 665 nm at 2.5-nm increments. The PDT damage was evaluated in serial Haematoxylin and Eosin stained sections using a tissue-damage scale. Light between 647.5 and 652.5 nm induced the highest damage to both the healthy and tumour mucosae. At wavelengths equal to or below 645 nm, and equal to or above 655 nm, tissue damage decreased. Wavelengths below 642 nm and above 660 nm did not induce any visible tissue damage. These results suggest that the in vivo optimal wavelength range for PDT with mTHPC is between 647 and 652 nm. This information is essential for selecting an appropriate light source