Natsuki Samejima

111In-labeled Mn-metalloporphyrin for tumor imaging

We synthesized and developed a new tumor imaging agent, 111In-labeled metalloporphyrin (111In-ATN-10) which consists of a carrier (ATN-10) of the tumor imaging possessing both a non-radioactive manganese complex in the porphyrin ring and a bifunctional chelating group (DTPA) attached to its side chain. The images of the three kinds of tumors were delineated more clearly by 111In-ATN-10 than 67Ga-citrate. Moreover, there was no photosensitivity in ATN-10. 111In-ATN-10 is studied as a new tumor positive scintigraphic agent instead of 67Ga-citrate.

A study on the vascular proliferation in tissues around the tumor in breast cancer

In order to study the vascular proliferation in human breast cancer, blood vessels were counted, per square millimeter, in the tissue immediately around tumors. Mastectomized specimens of 84 patients with breast cancer and specimens from 10 patients with benign mammary diseases were stained by hematoxylin eosin and, where required, by the avidin biotin peroxidase complex method for laminin staining. The vascular density around the breast cancer tissue was 20.35±8.40/mm2, which was significantly higher than the value of 13.44±5.85/mm2 for noncancerous mammary tissues (p<0.001) or the value of 12.65±4.12/mm2 for benign mammary disease tissues (p<0.01). Among the breast cancers, noninvasive carcinoma had a higher vascular density (28.44±6.15/mm2) than invasive carcinoma (19.73±8.22/mm2, p<0.02). According to the Japan Mammary Cancer Society Classification of invasive ductal carcinoma, vascularity was higher in the papillotubular type of cancer than in the solid-tubular or scirrhous types of cancer (p<0.02), although the papillotubular type had the lowest rate of nodal metastasis and vascular invasion as compared with the scirrhous and solid-tubular types. The vascular density around the tumors did not change in association with an increase in tumor size and it was suggested that blood vessels around a tumor would increase almost in proportion to the square of the tumor diameter.

TUMOR IMAGING WITH [111niIn]MONO-DTPA-ETHYLENEGLYCOL-Ga-DEUTEROPORPHYRIN

Abstract Mono‐DPTA‐ethyleneglycol‐Ga‐deuteroporphyrin (MDEGD) was synthesized, by coordinating non‐radioactive Ga in the porphyrin ring and connecting DTPA (diethylene‐triamine‐N,N,N,N,N,‐pentaacetic acid) to its side chain. By labeling with 111In, chemicals for scintigraphy were developed. They were applied to Syrian golden hamsters with implanted pancreatic gland cancers and C57‐black mice with Lewis lung cancer to enable tumor imaging and biodistribution examination. A comparative study was also conducted with [67Ga]citrate. In the resultant data, [111In]MDEGD showed larger tumor/lung, tumor/kidney and tumor/blood ratio with [67Ga]citrate. The affinity of [nIn]MDEGD in inflammatory tissue was much lower than that of 67Ga citrate. [111In]MDEGD lost its photosensitivity.

Detection and quantitative estimation of metalloporphyrins in vivo

Spectrofluorometry, radioisotope (RI) labelling and high performance liquid chromatography (HPLC) can be used to estimate photosensitizer concentrations. The biodistribution of porphyrins and metalloporphyrins containing the bifunctional chelating agent diethylenetriamine pentaacetic acid (DTPA) was examined in tumour-bearing mice by nitrogen-pulsed laser spectrofluorometry (PLS) and RI labelling. The biodistribution of metalloporphyrin amino acid derivatives containing alkoxyl groups was also examined by PLS and HPLC analysis using an acetone powder extraction method. Spectrofluorometry is useful for estimating the biodistribution of porphyrins in tumour, lung, kidney and serum, but not in liver. However, spectrofluorometry cannot be used to evaluate the concentration of certain metalloporphyrins such as manganese complexes. The concentrations of porphyrins in liver measured by PLS and two other methods showed remarkable differences. RI labelling and HPLC analysis are obviously tedious methods. Therefore it seems practical to screen for a number of compounds using the spectrofluorometric method (PLS). Subsequently, the porphyrins which give good results with PLS should be measured using RI labelling and HPLC.

Whole‐body Autoradiography of Tumor‐bearing Hamsters with a New Tumor Imaging Agent, Indium‐111‐labeled Porphyrin

We have synthesized a new tumor imaging agent, 111In‐labeled porphyrin (111In‐ATN‐2). In order to image transplantable pancreatic carcinoma in Syrian golden hamsters, we investigated the biodistribution of 111In‐ATN‐2 72 hr after injecting the agent by means of whole‐body autoradiography. The efficacy of the agent was compared with that of 67Ga citrate. The images with 111In‐ATN‐2 were found to be clearer than those with 67Ga citrate. Tumor‐to‐tissue radiodistribution ratios of the former were higher than those of the latter. Thus, 111In‐ATN‐2 seems to be more useful for tumor diagnosis.

Bone mineral analysis and X-ray examination of the bone in patients with biliary atresia

Investigations of bone mineral content, X-ray of the radius and ulna and serum biochemical analysis were performed in 10 children with biliary atresia (B.A.) and 150 healthy children. The patients were classified into 2 groups, namely; group A, comprised of 5 patients whose postoperative courses went well, and group B, comprised of 5 patients who developed various degrees of liver disturbance postoperatively. The ratio of bone mineral content (BMC) to bone width (BW) (BMC/BW) increased in accordance with age in the healthy children and the patients of group A, but was relatively slow in the patients of group B. Sings of rickets were found on the X-rays of 4 of the 10 patients, while serum levels of calcium and 25-OH-vitamin D in the group B patients were significantly lower than those in the group A patients or healthy children. Serum levels of alkaline phosphatase (Alp) fluctuated, but serum Alp was elevated in all the patients with rickets.

Drill needle biopsy for breast cancer

From 1977 to 1983 we have used electric drill needle biopsy of suspicious masses in the breast in 437 patients. In 104 patients with primary breast carcinoma 94 were diagnosed correctly by the initial biopsy, 9 were found on the second or third biopsy and one on the subsequent excisional biopsy. The rate of accuracy of the initial biopsy was 90.4 per cent. The diameters of the 104 carcinomas were less than 2 cm in 62 (59.6 per cent), 2–5 cm in 39 (37.5 per cent) and 5 cm or more in 3 (2.9 per cent). There were 17 patients (16.3 per cent) with a tumor 10 mm or less in diameter. Three hundred and thirty three patients had benign lesions. This drill needle biopsy method can be performed easily and accurately on nodules less than 2 cm, or even 10 mm or less nodules. For a diagnosis of early breast carcinoma made in the outpatient clinic or in screening examination programs, this method may be the most appropriate.

Radioisotopic splenoportography in patients with portal hypertension

Radio-isotopic splenoportography was performed by injecting99mTcO4− into the spleens of 46 patients with portal hypertension and 14 patients with various disorders not having portal hypertension. No collateral circulation was demonstrated in the 14 patients without portal hypertension whereas some RI-images of portosystemic collaterals were found in 40 (87.0 per cent) of the 46 patients with portal hypertension. Collaterals were divided into an ascending group and a descending group, the appearance rate of ascending collaterals being 80.4 per cent and that of descending collaterals, 41.3 per cent. There were 3 image patterns in the ascending group, namely, an AZ-pattern in which the azygos vein was demonstrated; a SC-pattern in which the RI-bolus ascended along the esophagus to the neck and the subclavian vein; and an EG-pattern which showed stagnation of the RI-bolus in the esophagogastric region. There were 4 patterns in the descending group, namely; a pattern of gastro-renal caval shunt (GR-pattern); reverse flow patterns into the umbilical or paraumbilical veins (UV-pattern); into the superior mesenteric vein (SMV-pattern); and into the inferior mesenteric vein (IMV-pattern). The appearance of the EG-pattern was seen most frequently (74.4 per cent). The usefulness of this method for surveying the collateral circulation in portal hypertension, estimating the risk of esophageal variceal bleeding and evaluating its treatments, was suggested by the results of this study.