Johan Areberg

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

Abstract: 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 bodys 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.

Accuracy of the quantification of organ activity from planar gamma camera images

The accuracy in determination of organ activity of (99m)Tc was investigated, with activity estimated from gamma camera images of phantoms, using the conjugate view method. The accuracy depends on several parameters such as the choice of background correction method, the accuracy in determination of the effective attenuation coefficient and the thickness of the body and organs and on the determination of the gamma camera sensitivity. The background correction method has a major influence on the quantification of the activity. Methods which take the volume of the source organ into consideration are recommended. The discrepancy in the determined organ activity varied between an underestimation of 26% and an overestimation of 16% in the MIRD phantom, depending on which organ was studied and on the correction method used. To correct for absorption and scattering, an effective attenuation coefficient was used. A theoretical analysis showed that a change in the effective attenuation coefficient of 0.01 cm(-1) resulted in a 15% change in the calculated activity. Also the thickness of the body and the organ of interest influences the calculated activity. A 2 cm deviation in the body thickness causes a deviation of approximately 10% in the calculated activity. The quantification is improved if the attenuation coefficient is determined by transmission measurements.

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.

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.

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.

Biodistribution and Kinetics of 191Pt in Patients Undergoing Therapy with Cisplatin

Cisplatin and carboplatin are two frequently used cytostatic agents. They are often combined with other drugs. Cisplatin is used in therapy of testis, head and neck, ovarian and bladder tumours. Individual variations in the therapeutic results are seen for patients receiving the same cytostatic drug treatment although they have the same histological form of cancer in the same stage.