Investigating the relationship between multimorbidity and dental attendance: a cross-sectional study of UK adults.

Introduction: Regular dental attendance is related to better oral health. However, long-standing health conditions (LSHCs) may be related to dental attendance and this relationship may vary by socioeconomic status. Method: Data were collected from wave two (2013­2015) of the Yorkshire Health Study (n= 7,654). Data included dental attendance, LSHC, age, gender, education-level, smoking, body mass index, and area-level deprivation. Logistic regression (attend or not) was used to analyse associations with LSHC and multimorbidity. Results: Overall, 63.1% (n = 4,826) of individuals attended the dentist. Of these, 37.8% (n =2894) had no LSHC, 26.0% (n = 1987) had one LSHC and 36.4% (n = 2784) had two or more LSHC. The presence of a singular LSHC was not associated with dental attendance(OR = 0.91 [0.81, 1.04]), however, those with two or more LSHCs were more likely to attend the dentist (OR = 0.81 [95% CI 0.72, 0.92]). Interactions between individual-level education, as a marker of socioeconomic status, and LSHC revealed few associations with dental attendance. Conclusion: Multimorbidity was associated with dental attendance such that those with multimorbidity were more likely to attend. These important findings highlight the increasing challenge of multimorbidity for global healthcare systems.

Mössbauer study of the '11' iron-based superconductors parent compound Fe(1+x)Te.

(57)Fe Mössbauer spectroscopy was applied to investigate the superconductor parent compound Fe(1+x)Te for x = 0.06, 0.10, 0.14, 0.18 within the temperature range 4.2-300 K. A spin density wave (SDW) within the iron atoms occupying regular tetrahedral sites was observed, with the square root of the mean square amplitude at 4.2 K varying between 9.7 and 15.7 T with increasing x. Three additional magnetic spectral components appeared due to the interstitial iron distributed over available sites between the Fe-Te layers. The excess iron showed hyperfine fields at approximately 16, 21 and 49 T for three respective components at 4.2 K. The component with a large field of 49 T indicated the presence of isolated iron atoms with large localized magnetic moments in interstitial positions. Magnetic ordering of the interstitial iron disappeared in accordance with the fallout of the SDW with increasing temperature.

The correlation of regression in primary melanoma with sentinel lymph node status.

BACKGROUND: The significance of regression in primary melanoma has been disputed for many years. Some have suggested regression as a marker for poor prognosis while others have reported a negligible or even a favourable effect, on prognosis. AIM: To understand the significance of regression in melanoma and provide further information on whether patients should be subjected to sentinel lymph node biopsy (SLNB) on the basis of regression. METHODS: 146 melanoma cases who had undergone SLNB were included in the study. The histological criteria for offering SLNB were melanoma >1 mm in thickness, Clark's level IV or those with regression. RESULTS: A statistically significant greater proportion of individuals without regression showed sentinel lymph node (SLN) positivity (p = 0.028) compared with those which do show regression. Metastatic disease correlated with growth phase of the primary lesion. All the node positive cases were in the vertical growth phase; none of the cases in radial growth phase and showing regression were associated with nodal metastasis (p = 0.029). 62 cases had melanomas with thickness <1 mm and were in radial growth phase, yet were offered SLNB because of regression. Of these, 44 showed features of regression and all were node negative. The remaining 16 cases of thin melanomas did not show regression; 2 of these had sentinel node metastasis. CONCLUSION: Results suggest that regression is usually a favourable process, particularly in thin melanomas and that metastasis in "thin melanomas showing regression" is real but rare. Variant vertical growth phase, mitoses and other prognostically significant variables may be more important predictors of metastatic potential in thin melanomas.

Functional outcome following modified Elmslie-Trillat procedure.

The aim of this study was to evaluate the mid- and long-term outcome of the modified Elmslie-Trillat procedure, as well as to detect factors affecting it. Thirty-eight patients (44 procedures) with a mean age of 31 years were included in this study. The reason for operation was patellar instability in 10 cases, anterior knee pain with malalignment of the extensor mechanism in 15 cases and a combination of both in 19 cases. Patients were followed for an average of 40 months (range=18-130 months). The functional outcome was very satisfactory or satisfactory for 73% of patients. According to Cox's criteria it was excellent in 13 cases (30%), good in 18 (41%), fair in 7 (16%) and poor in the remaining 6 (13%). Patients scored an average of 3.5 (range=2-8) in their Tegner Activity Scale, while their score in Activities of Daily Living Scale of the Knee Outcome Survey ranged from 43 to 98 (average=76). Result analysis revealed a better functional outcome when the operation was performed for patellar instability, as well as in the absence of grade 3 or 4 chondral changes in the patellofemoral joint at the time of operation. Elmslie-Trillat procedure satisfactorily restores patellofemoral stability and offers a very good functional outcome, especially in the absence of significant chondral changes in the patellofemoral joint at the time of operation.

Functional outcome following reconstruction in chronic multiple ligament deficient knees.

Multiligament knee injuries are rare but potentially limb-threatening conditions. In this study we aim to evaluate the mid- and long-term functional outcome of patients who underwent arthroscopically assisted multiple ligament reconstruction for chronic multiple knee ligament deficiency. Thirty-five patients (27 males and 8 females) with an average age of 35.1 years (range: 17-60) were included in this study. Follow-up ranged from 12 to 124 months (average: 40.3). On final follow-up patients had a mean loss of extension of 3.1 degrees , while flexion ranged from 95 degrees to 135 degrees (average: 118.4 degrees ). The functional outcome according to Clancy's criteria was excellent in 7 patients (20%), good in 14 (40%), fair in 11 (31.4%), while 3 reconstructions resulted in failure (8.6%). Patients scored an average of 4.03 (range: 1-9) in their Tegner Activity Scale, while their score in Activities of Daily Living Scale of the Knee Outcome Survey ranged from 25 to 98 with an average of 72.7. Sixteen patients returned to sporting activities and all but three returned to work. Early operative treatment of multiple ligament injuries is preferable, as it may allow for anatomic repair instead of reconstruction of ligamentous structures. This study demonstrates though, that even if acute reconstruction has not or could not be performed, reconstruction in chronic multiple ligament deficient knees should be attempted. Although this complex and technically demanding procedure rarely results in a "normal" knee, it offers in most cases very satisfactory stability and a significant improvement in knee function.

The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement.

PURPOSE: Sentinel node biopsy is now widely accepted as the most accurate prognostic indicator in melanoma, and is important in guiding management of patients with clinical stage I or II disease. Patients with a positive sentinel node have conventionally undergone completion lymphadenectomy (CLND) of the involved basin, but only 20% have involvement beyond the sentinel node, suggesting that CLND may be unnecessary for the other 80% of patients. This study seeks to identify criteria that might be used to be more restrictive in selecting those who should undergo CLND. METHODS: A total of 146 patients were identified who had had a positive sentinel node biopsy for malignant melanoma. Their sentinel nodes and lymphadenectomy specimens were re-evaluated pathologically. The metastatic melanoma in each sentinel node was assessed according to its microanatomic location within the node (subcapsular, combined subcapsular and parenchymal, parenchymal, multifocal, or extensive), and this was correlated with the presence of involved nonsentinel nodes in the CLND. The depth of the metastases from the sentinel node capsule was also recorded. RESULTS: The metastatic deposits in the sentinel node were subcapsular in 26.0% of patients. None of these patients had any nonsentinel nodes involved on CLND. In the patients whose sentinel node metastases had a different microanatomic location, the rate of nonsentinel node involvement was 22.2% overall. CONCLUSION: The microanatomic location of metastases within sentinel nodes predicts nonsentinel lymph node involvement. In patients with only subcapsular deposits in the sentinel node, it is possible that CLND could safely be avoided.

Novel gallium(III) complexes transported by MDR1 P-glycoprotein: potential PET imaging agents for probing P-glycoprotein-mediated transport activity in vivo.

BACKGROUND: Multidrug resistance (MDR) mediated by expression of MDR1 P-glycoprotein (Pgp) represents one of the best characterized barriers to chemotherapy in cancer patients. Positron emission tomography (PET) agents for analysis of Pgp-mediated drug transport activity in vivo would enable noninvasive assessment of chemotherapeutic regimens and MDR gene therapy. RESULTS: Candidate Schiff-base phenolic gallium(III) complexes were synthesized from their heptadentate precursors and gallium(III)acetylacetonate. Crystal structures demonstrated a hexacoordinated central gallium with overall trans-pseudo-octahedral geometry. Radiolabeled (67)Ga-complexes were obtained in high purity and screened in drug-sensitive (Pgp(-)) and MDR (Pgp(+)) tumor cells. Compared with control, lead compound 6. demonstrated antagonist-reversible 55-fold lower accumulation in Pgp-expressing MDR cells. Futhermore, compared with wild-type control, quantitative pharmacokinetic analysis showed markedly increased penetration and retention of 6. in brain and liver tissues of mdr1a/b((-/-)) gene disrupted mice, correctly mapping Pgp-mediated transport activity at the capillary blood-brain barrier and hepatocellular biliary cannalicular surface in vivo. CONCLUSIONS: These results indicate that gallium(III) complex 6. is recognized by MDR1 Pgp as an avid transport substrate, thereby providing a useful scaffold to generate (68)Ga radiopharmaceuticals for molecular imaging of Pgp transport activity in tumors and tissues in vivo using PET.

Synthesis of [(99m)Tc]DTPA-folate and its evaluation as a folate-receptor-targeted radiopharmaceutical.

A DTPA-folate conjugate was radiolabeled with (99m)Tc by stannous chloride reduction of [(99m)Tc]sodium pertechnetate in an aqueous solution of DTPA-folate. The radiochemical purity of the product consistently exceeded 97%, as assessed by thin-layer chromatography employing conditions analogous to those for radiochemical quality control of the radiopharmaceutical [(99m)Tc]DTPA. HPLC demonstrated that the radiolabeled product resulted from the intact DTPA-folate conjugate and not unconjugated DTPA. The ability of [(99m)Tc]DTPA-folate to target folate receptors in vivo was assessed in biodistribution studies with athymic mice bearing subcutaneous folate-receptor-positive human KB cell tumors. As an internal control, previously studied [(111)In]DTPA-folate was coinjected with the [(99m)Tc]DTPA-folate, along with varying amounts of DTPA-folate (0.38 mg/kg, 1.6 mg/kg, or 14 mg/kg). At each DTPA-folate dose, [(99m)Tc]DTPA-folate exhibited tumor uptake comparable to that of the coadministered [(111)In]DTPA-folate, with radiotracer levels declining at the higher DTPA-folate doses due to competitive receptor binding of the unlabeled conjugate. Tumor uptake of both tracers was also competitively blocked by preadministered folic acid dihydrate (2.9 mg/kg). Tumor-to-background tissue contrast obtained with [(99m)Tc]DTPA-folate was generally similar to that obtained with [(111)In]DTPA-folate. The (99m)Tc-labeled DTPA-folate conjugate may have utility as a targeted radiopharmaceutical for imaging neoplastic tissues known to overexpress the folate receptor.

Receptor-mediated targeting of 67Ga-deferoxamine-folate to folate-receptor-positive human KB tumor xenografts.

The radiochemical synthesis and stability of 67Ga-deferoxamine-folate ([67Ga]Ga-DF-Folate) were examined as a function of DF-Folate concentration. Optimal labeling occurred at DF-Folate concentrations > or =2.5 microg/mL. To define the possible biological significance of variations in product formulation, the biodistribution of [67Ga]Ga-DF-Folate was examined as a function of administered deferoxamine-folate dose in an athymic mouse KB tumor model. The folate-receptor-positive KB tumors were found to concentrate the 67Ga radiolabel in a dose-dependent fashion, consistent with saturable involvement of the folate receptor in mediating tumor accumulation of the radiopharmaceutical.

A kit formulation for preparation of [(111)In]In-DTPA-folate, a folate-receptor-targeted radiopharmaceutical.

A kit formulation has been developed for convenient, routine compounding of (111)In-labeled In(III)-DTPA-Folate, an investigational radiopharmaceutical for targeting tumor-associated folate receptors. The kit consists of the DTPA-Folate conjugate in sodium citrate solution, from which [(111)In]In-DTPA-Folate can be rapidly and reliably compounded by the addition of aqueous [(111)In]In(III)-chloride.

Indium-111-DTPA-folate as a potential folate-receptor-targeted radiopharmaceutical.

UNLABELLED: Indium-111-labeled diethylenetriamine pentaacetic acid (DTPA)-folate was evaluated as a radiopharmaceutical for targeting tumor-associated folate receptors. METHODS: Athymic mice were subcutaneously inoculated with approximately 1.8 x 10(6) folate receptor-positive KB (human nasopharyngeal carcinoma) cells, yielding 0.2- to 0.6-g tumors in 15 days, at which time (111)In-DTPA-folate, (111)In-DTPA or (111)In-citrate was administered by intravenous injection. RESULTS: The (111)In-DTPA-folate conjugate afforded marked tumor-specific (111)In deposition in vivo using this mouse model. The involvement of the folate receptor in mediating tumor uptake of (111)In-DTPA-folate was demonstrated by the blocking of tumor uptake by coadministration of free folic acid (intravenous). The (111)In-DTPA-folate also shows folate receptor-mediated uptake and retention in the kidneys, presumably reflecting radiotracer binding to folate receptors of the proximal tubules. In control experiments, the (111)In-citrate radiopharmaceutical precursor was also shown to afford significant tumor uptake of (111)In, but with much poorer tumor-to-background tissue contrast than that obtained with (111)In-DTPA-folate. Unconjugated (111)In-DTPA showed no tumor affinity. CONCLUSION: Indium-111-DTPA-folate appears suitable as a radiopharmaceutical for targeting tumor-associated folate receptors.

Selective antagonism of the GABA(A) receptor by ciprofloxacin and biphenylacetic acid.

1. Previous studies have shown that ciprofloxacin and biphenylacetic acid (BPAA) synergistically inhibit y-aminobutyric acid (GABA)A receptors. In the present study, we have investigated the actions of these two drugs on other neuronal ligand-gated ion channels. 2. Agonist-evoked depolarizations were recorded from rat vagus and optic nerves in vitro by use of an extracellular recording technique. 3. GABA (50 microM)-evoked responses, in the vagus nerve in vitro, were inhibited by bicuculline (0.3-10 microM) and picrotoxin (0.3-10 microM), with IC50 values and 95% confidence intervals (CI) of 1.2 microM (1.1-1.4) and 3.6 microM (3.0-4.3), respectively, and were potentiated by sodium pentobarbitone (30 microM) and diazepam (1 microM) to (mean+/-s.e.mean) 168+/-18% and 117+/-4% of control, respectively. 5-Hydroxytryptamine (5-HT; 0.5 microM)-evoked responses were inhibited by MDL 72222 (1 microM) to 10+/-4% of control; DMPP (10 microM)-evoked responses were inhibited by hexamethonium (100 microM) to 12+/-5% of control, and alphabetaMeATP (30 microM)-evoked responses were inhibited by PPADS (10 microM) to 21+/-5% of control. Together, these data are consistent with activation of GABA(A), 5-HT3, nicotinic ACh and P2X receptors, respectively. 4 Ciprofloxacin (10-3000 microM) inhibited GABA(A)-mediated responses in the vagus nerve with an IC50 (and 95% CI) of 202 microM (148-275). BPAA (1-1000 microM) had little or no effect on the GABA(A)-mediated response but concentration-dependently potentiated the effects of ciprofloxacin by up to 33,000 times. 5. Responses mediated by 5-HT3, nicotinic ACh and P2X receptors in the vagus nerve and strychnine-sensitive glycine receptors in the optic nerve were little or unaffected by ciprofloxacin (100 microM), BPAA (100 microM) or the combination of these drugs (both at 100 microM). 6. GABA (1 mM)-evoked responses in the optic nerve were inhibited by bicuculline with an IC50 of 3.6 microM (2.8-4.5), a value not significantly different from that determined in the vagus nerve. Ciprofloxacin also inhibited the GABA-evoked response with an IC50 of 334 microM (256-437) and BPAA (100 microM) potentiated these antagonist effects. However, the magnitude of the synergy was 48 times less than that seen in the vagus nerve. 7. These data indicate that ciprofloxacin and BPAA are selective antagonists of GABA(A) receptors, an action that may contribute to their excitatory effects in vivo. Additionally, our data suggest that the molecular properties of GABA(A) receptors in different regions of the CNS influence the extent to which these drugs synergistically inhibit the GABA(A) receptor.

Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical.

Folate-conjugated metal chelates have been proposed as potential imaging agents for cancers that overexpress folate receptors. In a previous study, folic acid was linked through its gamma-carboxyl group to deferoxamine (DF), and the 67Ga-labeled complex ([67Ga]DF-folate) was examined for in vivo tumor targeting efficiency in athymic mice with a human tumor cell implant. Although superb tumor-to-background contrast was obtained, slow hepatobiliary clearance would compromise imaging of abdominal tumors such as ovarian cancer. In the present study, folic acid was conjugated to an alternative chelator, diethylenetriaminepentaacetic acid (DTPA), via an ethylenediamine spacer. The desired DTPA-folate (gamma) regioisomer was synthesized by two different approaches, purified by reversed phase column chromatography, and characterized mainly by analytical HPLC, mass spectroscopy, and NMR. In cultured tumor cells, uptake of [111In]DTPA-folate (gamma) was found to be specific for folate receptor-bearing cells, and the kinetics of uptake were similar to those of free folate and other folate-conjugated molecules. In the normal rat, intravenously administered [111In]DTPA-folate (gamma) was found to be rapidly excreted into the urine, giving intestinal levels of radiotracer 10-fold lower than those observed with [67Ga]DF-folate (gamma) at 4 h. In a preliminary mouse imaging study, a folate receptor-positive KB cell tumor was readily visualized by gamma scintigraphy 1 h following intravenous administration of [111In]DTPA-folate (gamma).

CD44 expression in melanocytic lesions: a marker of malignant progression?

CD44 is the major human cell surface receptor for hyaluronate and functions in a diverse range of physiological processes. Alternative splicing of a single gene generates a family of splice variants (CD44vl-10) in addition to the standard isoform, CD44H. Expression of CD44, particularly CD44v6, has been described to correlate with metastasis formation in various tumours, although evidence in malignant melanoma is inconclusive. In this study, we explored the immunohistochemical pattern of CD44 expression in a range of melanocytic lesions using a panel of monoclonal antibodies raised to CD44H and the variants v3, v4/5, v6 and v8/9. Skin biopsies of 106 lesions from 100 patients were assessed and included benign and dysplastic naevi, melanoma in situ, malignant melanomas in horizontal and vertical growth phase, and cutaneous and lymph node metastases. CD44H was highly expressed in benign and dysplastic naevi and in melanoma in situ. However, expression with melanomas diminished with increasing invasiveness, and the pattern of expression observed correlated significantly with the growth phase of the lesion rather than its Breslow thickness. CD44 splice variants were not detected in any lesions. These results suggest a possible role for downregulation of CD44H in modulating the biological behaviour of malignant melanoma.

Tumor-selective radiopharmaceutical targeting via receptor-mediated endocytosis of gallium-67-deferoxamine-folate.

UNLABELLED: The receptor-mediated endocytosis uptake pathway for the vitamin folate was investigated as a target for tumor-selective radiopharmaceutical delivery. The molecular target for this delivery mechanism is a membrane-associated folate binding protein (FBP) that is overexpressed by a variety of malignant cell lines. METHODS: The ability of a 67Ga-labeled deferoxamine-folate conjugate (67Ga-DF-folate) to target tumor cells in vivo was examined using an athymic mouse tumor model. Subcutaneous inoculation of approximately 4 X 10(6) folate-receptor-positive KB (human nasopharyngeal carcinoma) cells into athymic mice yielded approximately 0.20 g tumors in 15 days, at which time either 67Ga-DF-folate, 67Ga-deferoxamine (67Ga-DF) or 67Ga-citrate was administered by intravenous injection. RESULTS: The 67Ga-DF-folate conjugate showed marked tumor-specific deposition in vivo, with 1.0 +/- 0.3% of the injected dose (%ID) in tumor at 4 hr postinjection (equating to 5.2 +/- 1.5 %ID/g tumor; n = 3 mice). Corresponding tumor-to-background ratios at 4 hr postinjection were: tumor/blood = 409 +/- 195; tumor/muscle = 124 +/- 47; tumor/liver = 11 +/- 3; and tumor/kidney = 2.6+/-0.9. Tumor uptake of 67Ga-DF-folate conjugate was effectively blocked by co-injection of 2.4+/-1.0 mg free folate. In control experiments, 67Ga-citrate exhibited tumor uptake of 2.2 +/- 0.4% of the injected dose (10.9 +/- 0.2 %ID/g tumor), but very poor target-to-background contrast (tumor/blood = 0.84 +/- 0.19; tumor/muscle = 5.4 +/- 0.7; tumor/liver = 2.3 +/- 0.2; and tumor/kidney = 2.4 +/- 0.3). Unconjugated 67Ga-deferoxamine showed no tumor affinity. CONCLUSION: Receptor-mediated endocytosis of radiolabeled folate-conjugates may offer a suitable mechanism for selectively delivering radiopharmaceuticals to tumors for diagnostic imaging and/or radiation therapy.

Respiratory health in asbestos-exposed ironworkers.

This study aimed to determine the prevalence of respiratory morbidity among asbestos-exposed ironworkers and to determine the relationship between respiratory morbidity indices and length of exposure. A medical screening provided information on chest radiographic abnormalities, pulmonary function, rales, finger clubbing, and respiratory symptoms for 547 asbestos-exposed ironworkers. Union pension records furnished data on length of exposure. The study group exhibited on increased prevalence of small irregular opacities, pleural plaques, and pleural thickening on chest x-ray; reduced FEF 25-75; rales; and respiratory symptoms. After controlling for the effect of cigarette smoking and age, years since joining the ironworkers union were significantly associated with profusion, pleural thickening, pleural plaques, rales, percent predicted FVC, reduced FVC, reduced FEV1, reduced FEV1/FVC, and dyspnea grades I, II, III, and IV.

Antioxidant depletion during aortic aneurysm repair.

Ischaemia-reperfusion injury generates oxygen-derived free radicals leading to local and distant damage. A simple method of following oxidative activity is to measure the consumption of endogenous scavenging antioxidants; an enhanced chemiluminescent assay was used to study this phenomenon in 21 patients undergoing surgery for abdominal aortic aneurysm (AAA). Samples of peripheral venous blood were taken before induction of anaesthesia and then from a central venous line and the inferior mesenteric vein before, during, and after clamping of the aorta. Further specimens were taken from the central line at 2, 6 and 24 h after operation. Antioxidant concentration in the peripheral, central and inferior mesenteric blood were similar, indicating that anaesthesia and surgical dissection had no effect. Levels decreased significantly in central and inferior mesenteric blood during and after clamping, but returned to normal by 24 h. These results confirm ischaemia-reperfusion phenomena in AAA repair.

Lymphocyte subset infiltration patterns and HLA antigen status in colorectal carcinomas and adenomas.

Fifty eight large bowel adenocarcinomas and 20 adenomas were studied immunohistochemically, using fresh frozen tissue sections, with regard to lymphocyte subpopulations (CD3, CD4, CD8, CD19, and CD20) in the inflammatory infiltrate and to expression of human leucocyte antigens (HLA-ABC, HLA-A2, and HLA-DR). The findings were related to differentiation and Duke's stage of carcinoma. The inflammatory infiltrate was found to have a phenotype that remained constant irrespective of the intensity of the inflammation. CD4 and CD3 positive cells predominated with fewer CD8 positive cells and a scanty diffuse CD19/20 positive cell population. CD19/20 follicular aggregates were common at the advancing margin of the carcinomas. There was no significant association with Duke's stage, differentiation or HLA status. HLA changes (ABC loss, A2 loss, and DR gain) were associated with differentiation, being more common and more extensive in poorly differentiated carcinomas. HLA-A2 loss was also associated with stage of progression of carcinoma. Inflammation associated with adenomas was found to have a similar phenotype to that associated with carcinomas. HLA changes in adenomas were uncommon, being seen in only one of our 20 cases.

Synthesis, purification, and tumor cell uptake of 67Ga-deferoxamine--folate, a potential radiopharmaceutical for tumor imaging.

The vitamin folic acid was covalently linked to the chelating agent deferoxamine (DF) via an amide bond using a simple carbodiimide coupling reaction. A mixture of two isomers, DF--folate(alpha) and DF--folate(gamma), was produced involving the alpha- and gamma-carboxyl group of folic acid, respectively. These two isomers were separated by anion-exchange chromatography using a NH4HCO3 gradient. Competitive binding studies revealed that only the DF-folate(gamma) is recognized by the folate receptor on KB cells, interacting with an affinity comparable to unconjugated folic acid. The DF--folate conjugates were radiolabeled with the gamma-emitting radionuclide 67Ga3+ and tested for uptake by cultured KB cells overexpressing the folate receptor. The cellular accumulation of 67Ga-DF-folate(gamma) tracer exhibited rapid uptake kinetics in cell culture with a t1/2 of approximately 3 min. The KB cell association of 67Ga-DF--folate(gamma) was competitively blocked by free folic acid, indicating that uptake of the 67Ga-DF--folate(gamma) was specifically mediated by the folate receptor. Since the folate receptor is overexpressed on the surfaces of many neoplastic cells, these results suggest that 67Ga-DF--folate(gamma) complex might be useful as a diagnostic agent for noninvasive imaging of folate receptor-positing tumors.