Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with 111In-CP04 in medullary thyroid carcinoma patients

Introduction: From a series of radiolabelled cholecystokinin (CCK) and gastrin analogues, 111In-CP04 (111In-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was selected for further translation as a diagnostic radiopharmaceutical towards a first-in-man study in patients with medullary thyroid carcinoma (MTC). A freeze-dried kit formulation for multicentre application has been developed. We herein report on biosafety, in vivo stability, biodistribution and dosimetry aspects of 111In-CP04 in animal models, essential for the regulatory approval of the clinical trial. Materials and methods: Acute and extended single dose toxicity of CP04 was tested in rodents, while the in vivo stability of 111In-CP04 was assessed by HPLC analysis of mouse blood samples. The biodistribution of 111In-CP04 prepared from a freeze-dried kit was studied in SCID mice bearing do

Efficacy and complications of neurosurgical treatment of acromegaly

The aim of the study was to evaluate the frequency of occurrence of pituitary failure following neurosurgery and the efficacy of transsphenoidal tumour resection in acromegalic patients. We retrospectively evaluated 85 patients (60 female and 25 male), of mean age 43.9 ± 13.2 years, treated by transsphenoidal neurosurgery. Macroadenoma and microadenoma of pituitary were found in 66 (77.6%) and 19 (22.4%) of these patients, respectively. Criteria of cure following neurosurgery were: basal GH < 2.5 μg/l, GH at 120 min in OGTT < 1.0 μg/l and serum concentration of IGF-1 within normal ranges for age and sex. After surgery 32 patients (37.6%) were cured and 53 patients (62.4%) required somatostatin analogue treatment. In patients cured by surgery, lower levels of basal GH (P < 0.05), IGF-1 (P < 0.001), GH at 120 min in OGTT and smaller size of pituitary tumour (P < 0.05) were found at diagnosis, as compared to patients in whom surgery was unsuccessful. Significant correlation between basal serum level of GH at diagnosis and size of pituitary tumour was found (P < 0.001). Invasive tumours were found in 45 of 53 (84.9%) patients not cured and in only 8 of 32 (25.0%) patients cured (P < 0.001). Impaired function of pituitary anterior lobe after surgery was observed in 30% and 4% of patients with macro- and microadenoma, respectively (P < 0.05). The efficacy of neurosurgery is affected by concentration of basal serum GH and IGF-1, GH at 120 min in OGTT, tumour size and invasiveness. Hypopituitarism after surgery is more frequent in patients with macroadenoma. Pituitary insufficiency, as a consequence of surgery, was found in 21% of patients with normal pituitary function prior to operation

Neuroendocrine neoplasms of the small intestine and the appendix - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of patients suffering from small intestinal NENs with distant metastases. The main cause of death in patients with carcinoid syndrome is carcinoid heart disease. The most useful laboratory test is the determination of chromogranin A, while concentration of 5-hydroxyindoleacetic acid is helpful in the diagnostics of carcinoid syndrome. For visualisation, ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, double-balloon enteroscopy, and somatostatin receptor scintigraphy may be used. A detailed his-tological report is crucial for the proper diagnostics and therapy of NENs of the small intestine and appendix. The treatment of choice is surgical management, either radical or palliative. The pharmacological treatment of the hormonally active and non-active small intestinal NENs as well as NENs of the appendix is based on long-acting somatostatin analogues. In patients with generalised NENs of the small intestine in progress during the SSA treatment, with good expression of somatostatin receptors, the first-line treatment should be radio-isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered

Somatostatin analogues : from research to clinical practice

Provides the most up-to-date coverage of somatostatin analog use in diagnostic and therapy Integrating the specialties of endocrinology, physiology, pathology, and nuclear medicine, providing the multidisciplinary approach to the topic Focuses on future applications, novel compounds, and areas for further research Covers topics by authors who are renowned experts and researchers in the fiel