Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11) C-Choline positron emission tomography/computerized tomography (PET/CT). After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 μg/L. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient

1011-116 Myocardial Rb Extraction Fraction: Determination in Humans

Ouantitation of myocardial blood flow (MBF) with diffusion-limited radiotracers as 82Rb and positron emission tomography (PET) requires knowledge of flow dependence of myocardial 82Rb extraction fraction. To determine this dependence we evaluated 7 patients (mean age (61.0±9.7) years, 4 males, 3 females) who had undergone coronary angiography with exclusion of relevant coronary stenoses and normal left ventricular function. 82Rb-PET clearance was simultaneously assessed with global MBF by the argon (Ar) inert gas method. 82Rb clearance was dynamically measured by a CTI-Siemens ECAT 931-08-12 scanner after i.v. injection of 1–1.2 GBq 82Rb. Ar gas desaturation was obtained by simultaneous arterial and coronary sinus blood sampling. Measurements were performed at rest and during vasodilatation induced by i.v. dipyridamole (0.7mg/kg/4min). Mean 82Rb clearance and Ar flow values were (0.39±0,03)ml/g/min and (0.69±0.14)ml/g/min at rest, respectively, and (0.47±0.09)ml/g/min and (1.48±0.49)ml/g/min during hyperemia. A fit with a two compartment model yielded E=PS/(PS+MBF) with PS=(0.82±0.09)ml/g/min (PS: permeability surface area product). These data (figure) provide for the best of our knowledge the first measured 82Rb extraction fraction in humans and may form the basis for more accurate quantitation of myocardial blood flow with 82Rb-PET

Synthesis and evaluation of F-18-fluoroethylated benzothiazole derivatives for in vivo imaging of amyloid plaques in Alzheimer's disease

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Synthesis, Radiolabelling and In Vitro Characterization of the Gallium-68-, Yttrium-90- and Lutetium-177-Labelled PSMA Ligand, CHX-A''-DTPA-DUPA-Pep

Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively) and resulted in nearly quantitative radiochemical yields within 5 min