Antitumor effect of radioactive cisplatin (191Pt) on nude mice.

PURPOSE: To investigate the effect of (191)Pt-cisplatin in vivo in terms of the antitumor effect and general toxicity on tumor-bearing nude mice. METHODS AND MATERIALS: Tumor-bearing (human squamous cell carcinoma, AB) nude mice were divided into four groups and given, i.p., physiological saline (controls), cisplatin, (191)Pt-cisplatin (80 MBq/mg), or (191)Pt-cisplatin (160 MBq/mg), respectively. Mortality and weight were used as parameters for monitoring general toxic effect, while specific growth delay (SGD) and the area under the logarithm of the relative tumor size curve (AUC-log[RTS]) were used to evaluate the antitumor effect of the treatments. RESULTS: Both SGD and AUC-log(RTS) values showed that (191)Pt-cisplatin was significantly (P < 0.05) more effective in retarding tumor growth than nonradioactive cisplatin. No differences in mortality between the different groups could be observed and no significant differences in weight change between the mice treated with cisplatin or (191)Pt-cisplatin could be seen. CONCLUSION: (191)Pt-cisplatin is a more effective drug than nonradioactive cisplatin in retarding tumor growth on nude mice without adding systemic toxic effects. We believe that radioactive cisplatin may prove to be an alternative to conventional cisplatin; however, the possible toxic effects on organs at risk have to be thoroughly investigated.

The prognostic value of body protein in patients with lung cancer.

Lung cancer is a major cause of death in many countries. To improve the results of treatment, more individualized therapy is necessary; for this, it is necessary to identify new prognostic factors. In 21 patients with lung cancer (17 with non-small-cell lung cancer and 4 with small-cell lung cancer) that had received radiation treatment, the amount of body protein was estimated with in vivo neutron activation analysis. Patients in whom body protein decreased had recurrences of the disease earlier and a poorer survival than patients whose body protein increased. A clear relationship was seen between changes in the body's protein content and recurrence-free survival. To better evaluate the prognostic value of body protein content in patients with lung cancer, a larger number of patients and a longer follow-up period are needed.

In vitro toxicity of (191)Pt-labeled cisplatin to a human cervical carcinoma cell line (ME-180).

PURPOSE: The aim of the present work was to examine the effect of (191)Pt-cisplatin, and to study the manner in which radiation and cisplatin interact, in a human cervical carcinoma cell line (ME-180). METHODS AND MATERIALS: The cells were incubated for 1 hour with nonradioactive cisplatin or (191)Pt-cisplatin with specific activities in the range 48-167 MBq/mg. The surviving fraction of the cells after 7 days' growth was determined with a nonclonogenic tetrazolium-based (MTT) assay. The uptake of platinum into the cell and the amount of platinum bound to DNA was measured. RESULTS: The 50% inhibition concentration (IC(50)) decreased with increasing specific activity of the (191)Pt-cisplatin. For the specific activities 0 (nonradioactive), 48, 89, 143, 157, and 167 MBq/mg, IC(50) was found to be 3.24 +/- 0.08, 2.77 +/- 0.55, 2.17 +/- 0.34, 1.15 +/- 0.04, 1.02 +/- 0.03, and 0.76 +/- 0.13 respectively. Isobologram analysis showed a supra-additive (synergistic) interaction between the radiotoxicity and chemotoxicity for specific activities over 100 MBq/mg. CONCLUSION: The cytotoxic effect of cisplatin may be enhanced by labeling the drug with the radionuclide (191)Pt.

Absorbed doses to patients from 191Pt-, 193mPt- and 195mPt-cisplatin.

Cisplatin, a chemotherapeutic drug, can be synthesized using radioactive platinum and then used for pharmacokinetic studies and tumor imaging. We have calculated the absorbed doses to various organs and tissues as well as the effective doses from 191Pt-, 193mPt- and 195mPt-cisplatin after administration to humans for diagnostic purposes. Liver was the organ that received the highest absorbed dose. The effective dose from 191Pt-, 193mPt- and 195mPt-cisplatin was 0.10 +/- 0.02, 0.17 +/- 0.04 and 0.23 +/- 0.05 mSv/MBq respectively.

A 252Cf-based instrument for in vivo body protein monitoring in cancer patients.

A hospital-based facility for in vivo prompt gamma neutron activation analysis of nitrogen for body protein determination is described. The patient is laid on a movable couch and is scanned with a vertically collimated neutron beam from a 252Cf neutron source (the amount of Cf varying from 120 to 40 microg due to the physical decay) positioned below the patient. Four large NaI(Tl) detectors are used to measure the 10.8 MeV gamma-rays from nitrogen. To check the long-term stability of the system, a solid phantom simulating the geometry of the adult human trunk, having similar elemental composition as tissue, was constructed. Repeated phantom measurements over 6 months gave a reproducibility in nitrogen determination of 2.9% (1 SD). Duplicate patient measurements carried out within a week showed a reproducibility of 5% (1 SD). A calibration method for absolute protein measurements in patients is presented. Patients are normally measured for 40 min; giving a mean whole-body equivalent dose of 0.25 mSv. Results from measurements on 13 cancer patients are presented.

Extensive chemical degradation of bleomycin during attempted labelling with 51-Cr.

AIM: Labelling of the cytostatic agent bleomycin with 51-Cr and use of the product for biodistribution studies have been reported in the literature. The labelling procedure involves incubation for 40 min at 130 degrees C. Since bleomycins are polar glycopeptides sensitive to hydrolytic cleavage we were concerned about possible degradation of the drug during these unfavourable conditions. We have therefore investigated the stability of bleomycin as a function of temperature and pH of the solution and attempted to achieve the maximum labelling efficiency with minimal degradation of the two principal bleomycin components. METHODS: The chemical stability of unlabelled bleomycin was investigated under labelling conditions at 130 degrees C and in buffer of pH 1-6 at room temperature (23 degrees C) and 60 degrees C. The samples were assayed by high-performance liquid chromatography (HPLC). The labelling efficiency of the 51-Cr-bleomycin complex was determined by thin layer chromatography and activity measurement with a high pure Germanium (HPGe)-detector at various incubation temperatures and times. RESULTS: Comparisons of rates of degradation of bleomycin with labelling efficiency as functions of temperature and time showed that under no condition could satisfactory labelling (> 97%) be obtained without considerable degradation of bleomycin. CONCLUSION: Labelling of bleomycin with 51-Cr does not yield a product suitable for investigations in patients.

Gamma camera imaging of platinum in tumours and tissues of patients after administration of 191Pt-cisplatin.

The aim of this study was to visualize non-invasively the uptake of platinum in tumours and tissues after treatment with cisplatin. 191Pt-cisplatin was synthesized from 191PtCl4 with rigorous pharmaceutical quality control. The uptake of platinum by both tumorous and healthy tissues was studied by gamma camera imaging in 14 patients, 5 of whom showed a clear uptake of platinum in regions corresponding to known tumour sites. Maximum concentrations of platinum in the tumours were on average 4.9+/-1.0 microg/g, when normalized to an administered amount of 180 mg cisplatin. In all the patients, the liver was the organ that showed the highest uptake. Platinum uptake was also seen in the spleen, gall bladder, gastrointestinal tract, bladder, kidneys, ureter, neck and mediastinum and urogenital region. By using in-house production of 191Pt-cisplatin, it was possible to monitor the uptake of platinum in tumorous tissues and healthy organs.

Body protein as a prognostic instrument for cancer patients?

Many cancer patients are affected by loss of appetite, weight loss and fatigue in the course of disease. These symptoms reduce the patients' quality of life, increase morbidity, and lessen tolerance to anti-tumor treatment. In some cases the symptoms are partly caused by various treatment modalities. The aim of this study was to investigate if radiotherapy affects the body weight and body protein of patients, and if changes in body protein have any clinical significance.