H. L. Atkins

A Fluorinated Glucose Analog, 2-fluoro-2-deoxy-D-glucose (F-18): Nontoxic Tracer for Rapid Tumor Detection

Rapid uptake of F-18 FDG was observed in a variety of transplanted and spontaneous tumors in animals. The tumor uptake reached a peak by 30 min and remained relatively constant up to 60 min, with a very slow wash-out of F-18 activity from the tumor thereafter. Tumor-to-normal tissue and tumor-to-blood ratios ranged from 2.10-9.15 and 2.61-17.82, respectively, depending on the type of tumor. A scintiscan of a seminoma in a dog showed very high uptake in the viable part and lack of uptake in the necrotic mass. Toxicological studies in mice using 1000 times human tracer dose (HTD) per wk for 3 wk and in dogs using 50 times HTD per wk for 3 wk did not show any evidence of acute or chronic toxicity.

Technetium-99m DTPA: a new radiopharmaceutical for brain and kidney scanning.

Abstract Technetium 99m was combined with the chelating agent DTPA in order to obtain a scanning agent with the physical properties of the radionuclide technetium 99m and the desirable biological properties of chelating agents. The method for the preparation of the chelate is described. No toxic effects are expected. About 90 per cent of the compound is eliminated by the kidneys in twenty-four hours. The absorbed radiation dose is 0.042 rad/mCi by the kidneys and 0.555 rad/mCi by the bladder. In clinical studies the chelate is useful for scanning of brain and kidneys and for vascular dynamic studies.

Myocardial Positron Tomography with Manganese-52m

The biodistribution of radiomanganese (54Mn) was studied in mice, rats, and dogs. Disappearance of radioactivity from the blood was extremely rapid, with a half-time of approximately 0.8 minutes. This resulted in very favorable myocardium-to-blood ratios, even at early times after administration. The myocardial uptake in dogs was greater than 3% at three and 15 minutes, with myocardium-to-blood ratios of about 40:1 at 15 minutes. Positron tomograms obtained with 52mMn clearly demonstrated regional myocardial perfusion. There was good correlation (r = 0.89) of microsphere-to-radiomanganese distribution in the infarcted dog heart.

Lymph Node Scanning with 99mTc-Sulfur Colloid

Technetium 99m was originally suggested as a possible medical tracer because of its ideal physical properties (1). Subsequently several technetium-99m-labeled radiopharmaceuticals were developed and are now widely used. One of them, 99mTc-sulfur colloid, has been employed for several years for scanning of the liver, spleen, and bone marrow (2). Studies in animals have shown that this radiocolloid preparation can also be used for lymph node scanning. In our experience with patients we have found that lymph node scanning with gelatin-stabilized 99mTc-sulfur colloid prepared by the H2S method is a simple, safe procedure and that scans of good quality can be obtained. Materials and Methods 99mTc-sulfur colloid was prepared by a procedure slightly modified from the one previously described (2). This method produces a colloid with particles substantially smaller than those produced by other commonly used methods. The particle size has not been determined precisely so far, but studies of the biological behavior ...

97Ru-transferrin uptake in tumor and abscess.

The uptake of97Ru-transferrin (Ru-TF) in tumor and abscess bearing animals was compared with67Ga-citrate (Ga),123I-transferrin (I-TF), and several other plasma proteins. Maximal concentration in tumor of Ru-TF in mice was three times higher than67Ga-citrate (16.80±4.20 vs 5.08±0.58% D/g) although it occurred later (24 h compared with67Ga which reached its maximum 2 h after injection). Whole body autoradiography (WBARG) with103Ru-transferrin (103Ru-TF) in tumor and abscess bearing rats demonstrated details of the distribution within these lesions. Turpentine-induced abscesses in the rabbits could be visualized with the gamma camera as early as 30 min post-injection of Ru-TF. It seems, therefore, that Ru-TF can be used for tumor and abscess localization. The results indicate that Ru-TF may have some advantages over67Ga-citrate because of the higher concentration in the lesions.123I-transferrin reached a concentration in tumor similar to67Ga (6.89±1.67 vs 5.08±0.58% D/g) but had a very low tumor to blood ratio (0.64). The three compounds investigated (Ru-TF, I-TF and ionic Ga, which binds instantaneously to TF in vivo) have a common lignad, transferrin. It appears, therefore, that tumor affinity is a property of the radionuclide-ligand complex rather than of the radionuclide itself.

INCREASED PLASMA LEVELS OF MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 IN LUNG AND BREAST CANCER ARE ALTERED DURING CHEST RADIOTHERAPY

PURPOSEnDoes the release of plasma matrix metalloproteinase-9 (MMP-9) by radiation-activated airway epithelial cells and infiltrating inflammatory cells play a role in the radiation damage or repair process in the lungs? We evaluated lung damage by ionizing radiation using plasma levels of MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and MMP-3 as biologic markers of tissue damage, and also their relationship to changes in pulmonary epithelial permeability, clinical signs and symptoms, and lung structural changes.nnnMETHODS AND MATERIALSnSeven serial studies were conducted in each of 8 patients undergoing chest radiotherapy (RT) for lung or breast cancer, beginning before the first treatment (baseline) and then biweekly to approximately 100 days during and after RT. Chest radiographs were monitored for each patient. Sandwich enzyme-linked immunoassays (ELISA) were used to measure plasma MMP-3, MMP-9, and TIMP-1 levels. Lung permeability was evaluated by measuring the rate of epithelial clearance of approximately 150 microCi ( approximately 5.6 MBq) inhaled (99m)Tc diethylenetriamine pentaacetate aerosol (DTPA).nnnRESULTSnLung and breast cancer resulted in very high plasma levels of MMP-9 (126-893 ng/mL) and TIMP-1 (496-8985 ng/mL) in all subjects studied before initiation of RT. This compares with plasma MMP-9 and TIMP-1 values in healthy volunteers of 29 +/- 11 ng/mL and 436 +/- 86 ng/mL, respectively. RT was followed by a sharp decrease in plasma MMP-9 within the first 2 weeks, but without a corresponding change in TIMP-1. In contrast, plasma MMP-3 levels, which are generally increased with inflammation, were elevated in only 1 of 5 subjects.nnnCONCLUSIONnLung and breast cancer are associated with high plasma levels of MMP-9 and TIMP-1. These high baseline plasma levels of MMP-9 were reduced in the first 2 weeks of RT in 7 of 8 subjects, and TIMP-1 plasma levels remained high in all subjects. The decrease in plasma MMP-9 after initiation of chest RT appears to reflect a suppressive effect on cancer-induced cellular responses rather than a primary role for MMP-9 in radiation-induced lung damage. Likewise, the lack of a rise in plasma MMP-3 levels does not support a role for MMP-3 in tissue injury or repair in the lung. It remains to be determined whether plasma MMP-9 measurements will serve as a useful parameter in predicting cancer relapse.

Distribution of 18F-5-fluorouracil in tumor-bearing mice and rats.

Extensive distribution studies of 18F-5-fluorouracil (18F-5-FU) in control and tumor-bearing mice (seven lines) and rats (eight lines) that have been shown or suspected to be responsive; to 5-FU treatment were investigated with 18F-5-FU. Studies were performed as a function of time, loading dose of 5-FU, and after a pretreatment regimen of 5-FU. Following the parenteral administration of 18F-5-FU to tumor-bearing mice and rats there was slight preferential uptake by some of the tumor types, particularly subcutaneous leukemic tumors and breast adenocarcinomas. The degree of concentration in tumor tissue in comparison with surrounding tissues (blood, muscle) was not such as to consider the radiopharmaceutical suitable for tumor localization. However, sufficient amounts of radioactivity localized in some tu,ors so that it might be possible to determine if a correlation exists between tumor uptake and anti-tumor effect of 5-fluorouracil. Another possible area of use might be in regulating the method of administration of the chemotherapeutic agent.

Erythropoietic and Reticuloendothelial Function in Bone Marrow in Dogs

Erythropoietic and reticuloendothelial functions in bone marrow were found to be identically distributed between various bones and within individual bones in the dog.

Evaluation of 99mTc-DTPA Prepared by Three Different Methods

Abstract Comparison of the biological behavior of three compounds containing DTPA and technetium 99m shows that only two of these compounds are true chelates. The third compound, produced with a kit (Renotec), is similar in behavior to that of the renal scanning agent 99mTc-Fe-ascorbic acid.

Scintigraphy with positron-emitting compounds.--I. Carbon-11 labeled thymidine and thymidylate.

Abstract The in vivo distribution of 11 C in normal and VX2 carcinoma-tumored rabbits has been observed with a gamma camera after i.v. doses of [ 11 C]thymidine or [ 11 C]thymidylate. The heart was visible immediately after injection of 11 C; the image disappeared by 5 min, indicating a rapid redistribution from the blood stream. We observed a generalized distribution of 11 C label with some notably “hotter” spots: tumor, bone marrow, liver. The liver, spleen and bone marrow were also visualized by 99 Tcm sulfur colloid injected before the [ 11 C]TdR or [ 11 C]dTMP. Injection of [ 11 C]TdR diluted with 60 times more nonradioactive TdR, 97 μmoles in all, resulted in a rapid excretion of 11 C. With 4 mCi of 11 C at injection time scintiphotos could be obtained up to 120 min.