Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer.

Phase I studies of [N-(2-hydroxypropyl)methacrylamide] (HPMA) copolymer-doxorubicin previously showed signs of activity coupled with 5-fold decreased anthracycline toxicity in chemotherapy-refractory patients. Here we report phase II studies using a similar material (FCE28068) in patients with breast (n=17), non-small cell lung (NSCLC, n=29) and colorectal (n=16) cancer. Up to 8 courses of PK1 (280 mg/m(2) doxorubicin-equivalent) were given i.

Delivery and collection of radioactive packages to and from UK hospital nuclear medicine departments.

Under radiation protection legislation in the UK, employers have a duty to maintain appropriate records to account for radioactive materials in their possession and to ensure security of these materials. This applies to radioactive packages, containing items such as technetium generators, which are regularly delivered to hospital nuclear medicine departments. It also applies to the collection of packages, such as those containing used generators for return to the supplier.

A comparison of SepPak and high-performance liquid chromatography as techniques for measuring the radiochemical purity of 99mTc-MAG3.

Objective: To compare high-performance liquid chromatography and SepPak as techniques for measuring the radiochemical purity of 99mTc-MAG3.

Methods: Samples of 99mTc-MAG3 (n = 20) with radiochemical purities in the range 43-98% were prepared and analysed by both techniques.

Results: The correlation between the results from the two techniques was excellent (r = 1.

Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin.

Purpose: Preclinical studies have shown good anticancer activity following targeting of a polymer bearing doxorubicin with galactosamine (PK2) to the liver. The present phase I study was devised to determine the toxicity, pharmacokinetic profile, and targeting capability of PK2.

Patients And Methods: Doxorubicin was linked via a lysosomally degradable tetrapeptide sequence to N-(2-hydroxypropyl)methacrylamide copolymers bearing galactosamine.

Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine.

Galactose-targeted delivery of macromolecules and drug conjugates to asialoglycoprotein receptor (ASGPR) positive cells has been widely documented in animals, although targeting in humans has never been demonstrated. In this study we report the pharmacokinetics and imaging determined in the first patient enrolled in a phase I clinical study of the poly[N-(2-hydroxypropyl)methacrylamide] copolymer bearing doxorubicin and galactosamine, known as PK2. Gradient high performance liquid chromatography (HPLC) evaluation of plasma and urine has been combined with 123I-based imaging to show biphasic clearance of the drug from the plasma (half-lives of 78+/-1 and 990+/-15), and approximately 30% delivery of the drug to the hepatic region, as determined by planar whole body imaging at 24 h.

Frequency of adverse reactions to radiopharmaceuticals in Europe.

A prospective survey was performed in 17 nuclear medicine departments during 1996 in an attempt to provide reliable data on the prevalence of adverse reactions to radiopharmaceuticals. All adverse events following radiopharmaceutical administration were recorded, irrespective of the severity or likelihood of causality, and subsequently analysed using an algorithm developed by Silberstein et al., designed to establish a cause-effect relationship.

A mechanism for professional and organizational audit of radiopharmacy departments.

An audit document is presented which can be used to assess the radiopharmacy service in a particular institute. It can be used for self-assessment or can form the basis for peer review. The document covers a wide range of aspects of radiopharmacy.

Drug interactions with radiopharmaceuticals.

Considerable information on documented drug and radiopharmaceutical interactions has been assembled in a tabular form, classified by the type of nuclear medicine study. The aim is to provide a rapid reference for nuclear medicine staff to look for such interactions. The initiation of drug chart monitoring or drug history taking of nuclear medicine patients and the reporting of such events are encouraged.

Effect of agitation on the quality of platelet concentrates.

Platelet concentrates (PCs) were stored for 4 days at 22 degrees C in 400 ml second-generation (PL1240) platelet packs with either constant agitation, manual mixing once every 24 h or without agitation at any time. After 4 days storage, in vivo recovery, survival and biodistribution were determined following indium-111 labelling of platelets and infusion into autologous volunteers. In vitro assays of platelet function and biochemistry were likewise carried out after 4 days storage.

White cell scans and infected joint replacements. Failure to detect chronic infection.

We report the results of imaging with labelled white cells in 52 patients before the revision of 54 cemented joint prostheses at which the diagnosis of infection was made from biopsies. Twenty-five hips were imaged with 111In-oxine-labelled cells; 20 hips and 11 knees were imaged with 99mTc-hexamethylpropylene-amineoxime-labelled cells. Of these, 13 hips and five knees proved to be infected.

Evaluation of the inflammatory infiltrate in pouchitis with 111In-labeled granulocytes.

Background: The aim of this study was to elucidate the inflammatory infiltrate in pouchitis and define the changes following metronidazole therapy.

Methods: Twenty-seven patients underwent functional grading, sigmoidoscopic and histological scoring, 111In-labeled granulocyte scanning, and 4-day fecal collections for 111In-labeled granulocyte excretion. Six of the patients with pouchitis underwent repeat studies after 1-month treatment with metronidazole, 400 mg three times daily.

Measurement of colonic transit time using radionuclide imaging: analysis by condensed images.

A polymer-coated capsule has been used in eight volunteer subjects to deliver 111In-resin into the ileocaecal region. The images were acquired for up to 3 days to follow transit through the colon. Expressing the results of individual studies is difficult and time-activity curves for each region are confusing.

Diffuse increase in renal uptake of technetium 99m methylene diphosphonate in association with disseminated cholangiocarcinoma.

A 48-year-old woman presented with disseminated cholangiocarcinoma and diffuse joint pain. A technetium 99m methylene diphosphonate bone scan revealed no bony abnormality, but intense bilateral renal uptake was seen. There was temporary renal impairment following imaging, but the cause of this is uncertain.

Pattern of radiopharmaceutical administration to patients between 1982 and 1986.

Analysis of the workload of a nuclear medicine department over the period 1982 to 1986 has shown the prevalence of repeated investigations in individual patients. Records from 23,152 investigations on 17,063 patients indicated that 88.5% received a single administration and only 0.

Implications of the ionizing radiations regulations for typical nuclear medicine departments.

The application of the 1985 Ionizing Radiations Regulations and Approved Code of Practice to a typical Nuclear Medicine Department has been considered. References to the Regulations are given so that their implications in a given department may be examined. The radiopharmacy, radioisotope dispensary and injection room will need to be Controlled Areas.

The value of syringe shields in a nuclear medicine department.

The radiation dose to the pulp of both index fingers has been measured in a radiopharmacy supplying 11 000 patient doses a year, in a hospital dispensary (4500 doses a year) and in its injection area. Tungsten syringe shields were used for one week and not used during the other week. In the radiopharmacy and the dispensary the highest finger dose recorded was 6.