Injection Of 67Ga Research Articles

Gallium-67 SPECT-CT for the evaluation of head and neck: preliminary study on maximum standardised uptake value in lesions, and in the parotid and submandibular glands.

PurposeThe aim of this study was to investigate the gallium-67 (67Ga) single-photon emission-computed tomography (SPECT-CT) for the evaluation of head and neck, especially maximum standardised uptake value (SUVmax) in lesions, and in the parotid and submandibular glands.Material and methodsFourteen patients with head and neck lesions who underwent SPECT-CT at 72 hours after injection of 67Ga were included in this study. The 67Ga SPECT-CT parameters SUVmax were compared between the parotid glands and submandibular glands. Statistical analyses for the SUVmax were performed by Mann-Whitney U test. A p value lower than 0.05 was considered as statistically significant.ResultsOf all 14 patients, 67Ga SPECT-CT was positive for two cases (one malignant lymphoma and one osteomyelitis). The SUVmax for malignant lymphoma and osteomyelitis were 11.21 and 10.95, respectively. Furthermore, SUVmax for parotid glands and submandibular glands of all patients were 4.86 ± 1.89 and 4.64 ± 1.64, respectively (p = 0.694).ConclusionsThis study investigated the 67Ga SPECT-CT for the evaluation of head and neck, especially SUVmax of lesions, and the parotid and submandibular glands. 67Ga SPECT-CT may be an effective technique for the evaluation of maxillofacial lesions.

Free 67Ga enters into the hepatocytes of carbon tetrachloride-treated rats

Gallium-67 ( 67Ga) has been used as tumor or inflammation-imaging agent in nuclear medicine for decades. Although many hypotheses concerning the mechanism of uptake of 67Ga into tumors and inflammation have been proposed, consensus has not been reached. If the mechanism of 67Ga uptake is clarified, we can improve the sensitivity of diagnostic imaging with 67Ga. We attempted to clarify the mechanism of 67Ga uptake by the liver of carbon tetrachloride (CCl 4)-treated rats. First, we investigated whether or not transferrin (Tf) is involved in 67Ga uptake by the liver tissue of CCl 4-treated rats. It is well known that Fe 3+ can inhibit the binding of 67Ga to Tf. The administration of FeCl 3 5 min before the injection of 67Ga slightly enhanced the uptake of 67Ga by the liver tissue of CCl 4-treated rats. The entering of 67Ga into hepatocytes of CCl 4-treated rats was similar to the uptake by the liver tissue. In addition, the administration of FeCl 3 slightly increased the entering of 67Ga to hepatocytes. These results suggest that free 67Ga enters into hepatocytes from the liver of CCl 4-treated rats.

Transferrin is not involved in the entry of 67Ga into hepatocytes from regenerating liver of partially hepatectomized rats.

Ever since the first observation of 67Ga accumulation in tumors and inflammatory lesions, 67Ga has been used to detect various tumors and inflammations. The aims of this study were to clarify whether or not transferrin is involved in the uptake of 67Ga by the regenerating liver after partial hepatectomy. The uptake of 67Ga by the liver of rats reached a maximum 2 d after partial hepatectomy. In order to inhibit the binding of 67Ga to transferrin in the blood, FeCl3 was administered 5 min before the injection of 67Ga. The administration of FeCl3 decreased the uptake of 67Ga by the liver of the partially hepatectomized rats, suggesting that transferrin is involved in the uptake by the liver. However, 67Ga was taken up only slightly by hepatocytes obtained from the liver of these rats. We conclude that transferrin is involved in the uptake of 67Ga by the liver tissue of partially hepatectomized rats but is not involved in its entry into the hepatocytes. Only a slight amount of gallium-67 enters the hepatocytes, and may accumulate primarily in the extracellular matrix of the liver tissue of these rats.

The influences of dexamethasone and indomethacine on 67Ga uptake by normal tissues.

Dexamethasone (DEX) increased 67Ga uptake by the liver and spleen at 4, 8, and even 24 h after the injection of 67Ga. These results showed that DEX influenced 67Ga accumulation as well as the initial entry of 67Ga in the liver and spleen. On the other hand, indomethacin (IM) decreased 67Ga uptake by the liver and spleen at 4 h after the injection of 67Ga but did not influence the uptake at 8 or 24 h after the injection of 67Ga. Moreover, DEX or IM little influenced 67Ga uptake by the kidney and muscle. These results suggest that the influence of DEX or IM on 67Ga uptake or accumulation is specific for the liver and spleen.

Lacrimal gland accumulation of 67Ga-citrate in patients with Sjögren's syndrome.

The extent of 67Ga accumulation in the two lacrimal glands in patients with keratoconjunctivitis sicca (KCS) of Sjögren's syndrome was studied. Of the two main groups one consisted of 69 subjects without ophthalmic complaints (control group), the other consisted of 26 patients with KCS of Sjögren's syndrome. Of the 26 patients with KCS, 7 had been diagnosed as probable KCS (probable sub-group) and the other 19 had been diagnosed definite KCS (definite sub-group). About 3 mCi (111 MBq) 67Ga-citrate was injected IV into each subject and this was followed by scintigraphy at 24, 48, and 72 h after the injection of 67Ga. A positive finding in the lacrimal gland was noted in 64 of 69 subjects (92.7%) in the control group and in 7 of 7 patients (100%) with probable KCS. Three of 19 patients with definite KCS (15.7%) showed positive findings under scintigraphy. When the scintigraphic finding in the lacrimal gland is not positive in patients with suspected KCS of Sjögren's syndrome, they can then be diagnosed with little risk as definite KCS cases. Shirmer's test was performed on subjects in the probable and definite groups. There was statistical significance between the positive and equivocal or negative scintigraphic finding and Schirmer's values. These results suggest a correlation between gallium accumulation in the lacrimal gland and the tear production.

67Ga accumulation and heparan sulfate metabolism in lysosomes.

67Ga incorporation in the mitochondrial-lysosomal (Mt-Ly) fraction of rat liver increased sharply from 1 to 24 h after 67Ga IV injection, whereas that in the 105,000 g supernatant fraction decreased sharply from 6 to 48 h. Further, when 14C-labeled heparan sulfate (HS: biosynthesized by injection of [1-14C] glucosamine into a rat) was injected intravenously into a rat treated with Triton WR-1339, and the liver was isolated and fractionated, the radioactivity of 14C was concentrated in the lysosomal fraction. The effect of HS on 67Ga uptake in normal rat liver was also studied. On administration of 67Ga-HS complex, the peak uptake of administered radioactivity of 67Ga in rat liver occurred sooner than after the injection of 67Ga alone. The change was greatest in the Mt-Ly fraction among the subcellular fractions. Moreover, the 67Ga uptake in rat liver increased with increasing doses of HS. These results suggest that administered 67Ga may be bound to HS and that the concentration of 67Ga in lysosomes may be related to the in vivo metabolism of HS.

Relative tumour enhancement of 67Ga uptake by desferrioxamine.

The administration of the iron- and gallium-chelating agent, desferrioxamine (DFO), to mice after the injection of 67Ga has been shown to improve tumour to normal tissue ratios. Time and dose parameters have been studied. The optimal time was about 7 h after 67Ga, when the tumour to blood ratio was increased 16 times compared with controls. The effect was due to the greater retention of 67Ga in tumour compared with other tissue. Tumour retention after DFO was 78% compared with controls at 7 h, giving a tumour to blood ratio of 25.9. Tumour retention of 67Ga correlated well with the proportion of cell-bound activity which was localised in the lysosomes. Prior administration of iron increased lysosomal accumulation of 67Ga in tumour cells, and hence the retention of the nuclide after the use of DFO.

Deferoxamine mesylate enhancement of 67Ga tumor-to-blood ratios and tumor imaging.

To improve the tumor-to-blood ratio in 67Ga tumor imaging, the effect of administration of deferoxamine mesylate (DFO) was evaluated. DFO improved 67Ga tumor-to-blood ratios in tumor-bearing rats. Administration of DFO 12 h after 67Ga injection did not decrease the concentration of radioactivity in the tumor of rats, but administration of DFO 4 h after 67Ga decreased the concentration of radioactivity in the tumor. Serum unsaturated iron binding capacity in rats was transiently increased by DFO administration, but when DFO was administered before 67Ga injection the tumor uptake showed rather decreased levels. In human studies, DFO accelerated the excretion of 67Ga from the blood, but tumor images were not necessarily improved.

Mechanisms of distribution of gallium 67 in mouse tumour hosts.

In several mouse tumour models iron given parenterally not only inhibited the transport of 67Ga by plasma transferrin but also accelerated the binding of 67Ga in tumour tissue, particularly during the first hour after 67Ga injection. By 30 min, the tumour had already attained a high concentration though the 67Ga accumulated was still potentially reversible. With the passage of time equally high 67Ga concentrations were attained in tumour in iron-treated and untreated animals alike, and were maintained high as 67GA was totally cleared from the plasma. Given IV, 125-I-human transferrin was not preferentially bound in tumour whereas in muscle tissue loaded with transferrin, 67Ga was accumulated locally during the immediate post-injection phase and to an enhanced degree in iron-treated animals. A hypothesis is presented which, by drawing attention to the role of extravascular transferrin in binding and presenting 67Ga for cellular uptake, helps resolve the apparent contradictions between in vivo and cell culture findings.

Leukocyte and 67Ga-citrate dynamics in experimental subcutaneous Streptococcus faecalis infections.

The dynamics of white blood cell (WBC) and 67Ga-citrate accumulation were studied in rabbits with subcutaneous polyethylene chambers. Uninfected chamber fluid (CF) contained less than 1,000 WBCs/mm3, most of which were mononuclear. After 67Ga injection, radioactivity increased slowly in uninfected fluid, peaked between 24 and 48 hours, and then gradually decreased. 67Ga scans showed no uptake in excess of background levels around the uninfected chambers. After injection of Streptococcus faecalis directly into the chambers, bacterial concentrations initially decreased, increased by 4-24 hours, and then decreased slightly. WBCs began to increase 4 hours after infection due to influx of polymorphonuclear leukocytes. 67Ga localized in infected chambers before the increase in WBCs. Use of the subcutaneous chamber model could help elucidate the mechanism(s) of 67Ga accumulation at sites of inflammation.

The effect of the administration of iron on gallium 67 citrate uptake in tumours.

Consideration has been given to the use of iron as an aid in 67Ga scanning. The effects of various doses and the time of injection have been measured quantitatively in four transplantable rodent tumours. It was found most effective to administer the iron, as ferric ammonium citrate, before the 67Ga injection. The experimental tumours respond to different extents, and the tumour:non-tumour ratios at four hours after 67Ga injection have been found to be from two to four times better than those obtained at 24 hours with 67Ga alone. The effects of administered iron on the rate of blood clearance and the plasma binding of 67Ga have been measured. The use of carrier gallium or scandium was found to be less advantageous than the use of iron.

Modification of distribution of gallium 67 in man by administration of iron.

In mice bearing tumours, the clearance of 67Ga from blood and the attainment of high tumour-to-normal soft-tissue concentration ratios are accelerated if the serum unsaturated iron-binding capacity (UIBC) is low. A preliminary clinical trial is described, concerning the administration of iron as a means of creating favourable imaging distributions within 6 h of injection of 67Ga. Iron was given intramuscularly at a dosage in the range 50-100 mg, depending on the patient's UIBC and generally about 3 h post 67Ga. In 14 patients receiving iron, consistent and substantial reductions in 67Ga plasma concentrations and in UIBC were demonstrated. In seven of these, the 6 h 67Ga images revealed lesions at contrasts which were nearly equivalent to their contrasts in later (48 h) pictures: there were an additional two cases where the lesion was not detected until 48 h. The 6 h results were relatively free of the bowel appearances which sometimes confuse later studies, and examinations generally benefited from the advance information gained at 6 h.

Effects of desferrioxamine on 67Ga distributions in tumor-bearing mice.

The iron-chelating agent desferrioxamine caused approximately 10-fold reductions in 67Ga vascular concentrations and substantial (~ × 2) reductions in 67Ga concentrations of other tissues when injected iv into mice at 2 hr after 67Ga injection. Given 48 hr post 67Ga however, its only noteworthy effect was on the vascular compartment. Tumor was distinguished from other soft tissues by high concentrations of cell-bound 67Ga, of which an appreciable fraction could be chelated and cleared by desferrioxamine given 2 hr after 67Ga. This fraction diminished with time and, at 48 hr, desferrioxamine caused no significant clearance of tumor-bound 67Ga.

Desferoxamine Mesylate (Desferal): A Contrast-Enhancing Agent for Gallium-67 Imaging

Desferal (desferoxamine mesylate) was investigated as a contrast-enhancing agent for tumor and abscess imaging with 67Ga-citrate. Tumor studies were performed in mice with Cloudman S-91 melanoma. Abscess studies were performed with a subcutaneous abscess model in rabbits. When Desferal is administered 16 to 18 hours after injection of 67Ga, rapid blood clearance of 67 Ga occurs with only slight (tumor) or no (abscess) loss of activity from the lesion. Retention in other organs is variable. Tumor-to-blood ratios are improved eightfold in tumor and fourfold in abscess in studies performed with single Desferal injections of 150 mg/kg. Blood and total body clearance studies in rabbits reveal that maximum Desferal effect is achieved in the 17 to 50 mg/kg dose range and that only minimal improvement occurs at higher doses.

Studies of Gallium Accumulation in Inflammatory Lesions

The kinetics of 67Ga accumulation in experimental inflammatory exudates were studied. In six rabbits with S. aureus induced abscesses, serial samples of exudate and blood were obtained at 1, 2, 4, 24 and 48 hrs after intravenous injection of 67Ga. The accumulation of 67Ga in the inflammatory exudate was slow with an accumulation half-time of 5.5 hrs. The concentration of 67Ga in the abscesses approached that of blood 48 hrs after injection. Analysis of the distribution of 67Ga in the inflammatory exudate revealed that the portion of 67Ga in the cellular fraction (1,600 xg pellet) correlated best with the number of non-viable polymorphonuclear leukocytes (PMN) (r = 0.81). Its correlation with total number of PMN and bacteria was r = 0.69 and r = 0.35, respectively. Autoradiographic studies confirmed that the majority of 67Ga in the cellular fraction of the exudate was associated with non-viable PMN's.