A.B. Brill

The development and in-vivo behavior of tin containing radiopharmaceuticals—I. Chemistry, preparation, and biodistribution in small animals☆

Tin is an essential ingredient of most technetium-99m radiopharmaceutical preparations but its in-vivo distribution and long-term fate are not well understood. Tin-117m (t1/2 14d; gamma 159 keV, 86%) is an ideal tracer for studying biological behavior of tin compounds as well as for developing clinically-useful radiopharmaceuticals. This work describes the preparation and in-vivo distribution in mice of a number of tin-117m labeled compounds with commonly used ligands. High bone uptake of most compounds studied as well as the unexpectedly high bone uptake of Sn4+-DTPA indicates a high bone affinity of tin bound to chemically diverse ligands. Various compounds show subtle but significant differences in blood clearance, excretion, and soft-tissue uptake. Differences among Sn2+ and Sn4+ compounds with the same ligand are particularly noteworthy. For stannic chelates, higher bone uptake, faster blood clearance, and reduced soft-tissue concentration were observed. It appears that tin compounds bind to bone predominantly through the tin atom and that the differences in biodistribution depend on factors such as the net charge on the complex, the oxidation state of tin, and hydrolytic and kinetic stabilities of the complexes. The results indicate that the favorable half-life and decay characteristics of tin-117m in various stannic compounds, especially stannic-DTPA, make it potentially useful as an agent for skeletal scintigraphy and radiotherapy of bone tumors.

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.

131I-metaiodobenzylguanidine uptake in the isolated rat lung: A potential marker of endothelial cell function

The pulmonary vascular endothelial cell plays an important role in the uptake of circulating biogenic amines. In cultured adrenomedullary cells, metaiodobenzylguanidine (MIBG) and norepinephrine (NE) are taken up by the same sodium-dependent active transport system. To examine whether a similar process occurs in the lung, the mechanism of single pass 131I-MIBG accumulation was studied in rat lungs perfused with a Krebs-Ringer bicarbonate buffer containing 4.5% bovine albumin. MIBG lung accumulation was measured as the percent extraction per g of lung tissue. In control experiments the extraction was 19.7±2.3%/g (n=38) using a perfusate containing 0.01 μM MIBG. MIBG accumulation was significantly depressed (% decrease from control) by: cold media at 4° C (84%), 0.5 mM ouabain (67%), 10 μM imipramine (70%), 0.7 μM serotonin (22%) and 40 mM K+ (48%). Pulmonary uptake of MIBG was characterized by Michaelis-Menten kinetics (Km=0.92×10-6 M and Vmax=2.09×10-9 moles/g per min). The addition of NE (0.5 μM) also altered MIBG uptake such that the Km and Vmax became 0.52×10-6 M and 0.93×10-9 moles/g per min, respectively. The results indicate that MIBG accumulation in the lung involves sodium-dependent, energy-requiring, active transport mechanisms similar to those known to exist for norepinephrine, and suggest that MIBG may be useful as a marker of pulmonary endothelial cell function.

The effect of diphenylhydantoin (Dilantin) on thallium-201 chloride uptake

The effect of diphenylhydantoin (Dilantin) on the myocardial uptake of 201Tl-chloride was studied in rats. Prior administration of Dilantin caused a significant (38.8) decrease in 201Tl uptake compared with the control group. No significant change in heart to blood or heart to muscle ratios was observed. Administration of Dilantin after 201Tl-chloride did not affect the myocardial concentration of the radionuclide.

Desferal (DFO) induced 67Ga washout from normal tissue, tumor and abscess in experimental animals

In the experimental animal, desferal (DFO) given intravenously washes out Ga-67 from all tissues. This effect is not uniform: blood activity is reduced very markedly, while liver activity is less affected. Maximal effect of DFO occurs if given close to the Ga-67 injection. When the time interval between the two is increased, the absolute amount of Ga-67 excreted in the urine in excess of the spontaneous excretion is reduced. Administration of DFO does not effect Ga-67 gastrointestinal excretion. In three animal tumor models (EMT-6 sarcoma in Balb/c mice, spontaneous adenocarcinoma in mice, and spontaneous adenocarcinoma in the rabbit) and in sterile abscess-bearing rats, the administration of DFO 24 hrs after Ga-67-citrate improves significantly the target-to-nontarget ratio. Animals given 50 mg/kg DFO I.V. after Ga-67 citrate showed a significant reduction in the whole-body activity as seen in a one-week follow up.