Tumor-seeking Agent Research Articles

Medical Applications of Laser Spectroscopy

Lasers are finding many applications in medicine and biology. While most laser use focuses on the heat generation of the laser beam interacting with tissue, spectroscopic aspects play a more dominating part in a number of emerging applications. Tumour-seeking agents, such as hematoporphyrin derivative (HPD), in combination with laser radiation provide new possibilities for cancer tumour detection and treatment. The fluorescence emission from tissue irradiated with UV light can be used for tumour localization. Natural tissue fluorescence as well as fluorescence due to injected HPD can be utilized. Results from studies on animals and from clinical applications are reported. The use of fluorescence for identifying atherosclerotic plaque in human vessels is illustrated. Spectroscopic analysis of the laser-induced plasma obtained when a high-power, pulsed laser beam interacts with tissue is also discussed with applications to plaque removal and laser fragmentation of kidney- and gall-stones.

Aspects of tumour demarcation in rats by means of laser-induced fluorescence and haematoporphyrin derivatives

The effects of different parameters of interest for the localization of malignant tumours in situ by means of laser-induced fluorescence and haematoporophyrin derivatives were investigated. Such parameters are drug composition, drug concentration, laser pulse energy and excitation wavelength. In order to assess the relative merits of the tumor tumour-seeking agents Photofrin (haematoporphyrin deriative) and Photofrin II (dihaematoporphyrin ether) we have performed a comparative study on rat tissues. The results suggest that Photofrin is at least as good as the therapeutically more potent agent Photofrin II. A linear relation between drug dose and recorded prophyrin fluorescence intensity was also found. Using not only the porphyrin fluorescence, but also natural tissue autofluorescence, better tumour demarcation is observed when utilizing an excitation wavelength shorter than the porphyrin excitation peak at 405 nm.

Fluorescence endoscopy instrumentation for improved tissue characterization.

An endoscopic instrument for normal optical inspection and simultaneous fluorescence characterization is described. The equipment is primarily intended for early cancer detection using characteristic fluorescence from the tumor-seeking agent hematoporphyrin derivative. A dimensionless ratio of two fluorescence intensities is monitored making the equipment insensitive to target distance and surface topography. A measurement example is given and possible improvements are discussed.

Investigation of 99mTc labeled tumor seeking agents--usefulness of 99mTc-isoniazid

For the development of 99mTc labeled tumor seeking agents, 273 drugs and chemicals were evaluated. Agents labeled by SnCl2-HCl method were injected to rats bearing Yoshida sarcoma. Scintigrams of the rats 2 hours after injection and the excised tumor and organs placed on a plate were taken and evaluated their affinity to the tumor. Isoniazid (INH) was found to be the most useful agent as a result of this screening study. Intensive study on 99mTc-INH was subsequently performed. Another labeling method, FeSO4-H2SO4 method, was evaluated and shown to be superior in both absolute tumor uptake and tumor to muscle ratio. Uptake of 99mTc-INH to Yoshida sarcoma occurred early after injection and maintained its level until later time. On the other hand, radioactivity in the blood and muscle decreased rapidly; that is, tumor to blood and muscle ratio showed rapid increase. Other animal tumor models, mouse bearing Ehrlich tumor or Sarcoma 180, were also used to evaluate the usefulness of 99mTc-INH. The labeled agent showed good localization in these tumors too. In conclusion 99mTc-INH might be a good tumor seeking agent and further clinical trials would be warrant.

Medical Diagnostics Using Laser-Induced Fluorescence

Tumour-seeking agents, such as hematoporphyrin derivative (HPD), in combination with laser radiation provide new possibilities for cancer tumour detection and treatment. The fluorescence emission from tissue irradiated with UV light is used for tumour localization. The development of techniques for maximum discrimination between tumours and normal tissue is of particular interest. Natural tissue fluorescence as well as fluorescence due to injected HPD will be discussed. Results from studies on rats and mice are reported. The use of fluorescence for identifying atherosclerotic plaque in human vessels is also illustrated. The development of clinical instrumentation for point measurements and imaging is discussed.

Initial results of immunolymphoscintigraphy in the diagnosis of axillary lymph node involvement in breast cancer patients

Sixteen patients suffering from breast cancer were investigated by the method of immunolymphoscintigraphy (ILS) to evaluate the axillary lymph node status. Two monoclonal tumour associated antibodies (HMFG-1 and HMFG-2) that are known to react strongly with a wide range of epithelial malignomas were used as tumour seeking agents in our recent study. All patients were operated a few days after the scanning procedure including a radical axillary lymph node dissection. Therefore the scan reports could be correlated in each case with the histology of the surgically removed probes. While HMFG-1 failed to show correct results, HMFG-2 gave accurate results in 9 of 13 cases of questionable lymph node involvement. Among the 4 false results, one turned out to be false positive and three false negative. If better antibodies or their fragments, respectively, are used, we are convinced this noninvasive approach will greatly improve preoperative diagnosis of lymphatic involvement in breast cancer patients.

Biodistribution of A14C-and99mTc-labeled N-substituted nitrosourea (CCNU) in an animal tumor model

One formulation of14C labeled and another of99mTc labeled 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) were administered i.v. to tumor (glioma) bearing rats. The radiopharmacokinetics of14C-CCNU were followed up to 24 hours post injection. On a per organ basis the blood, liver, small bowel, kidney cortex and muscle contained most of the activity. Optimum tumor to organ ratios occurred at 4–12 hours. The99mTc-CCNU biodistribution was determined at 4 hours and compared to99mTc-NaTcO4. Tumor capsule to brain (29.5) and to muscle (10.59) ratios suggest99mTc-CCNU to be a potential tumor seeking agent.

False positive bone scan in bone tumors of the lower limb.

When examined using bone scanning agents, eight out of nine patients with lower limb malignancy, and neither of two affected in the upper limb showed a pathologic focus of isotope uptake in an area distal to the tumor. On pathologic examination the positive findings proved false. Such misleading results were found to be avoidable if a tumor-seeking agent instead of a bone scanning one is used.

57-cobalt-bleomycin as a tumor scanning agent in primary hepatocellular cancer.

57Co-bleomycin and 99mTc-sulfur colloid scans were performed in 13 southern African black patients with primary hepatocellular cancer (PHC) and 3 patients with other space-occupying hepatic lesions. Selective concentration of 57Co-bleomycin in the defect or defects seen on the 99mTc-sulfur colloid scan occurred in only 4 of the 13 (31%) patients with PHC. In the remaining PHC patients, as well as in the 2 patients with metastatic liver disease and the 1 patient with an amebic liver abscess, the 57 Co-bleomycin and 99mTc-sulfur colloid scans were identical. 57Co-bleomycin appears to have only a limited place as a tumor-seeking agent in the diagnosis of PHC in southern African blacks.