The Vienna protocol and perspectives in radionuclide therapy.

The Vienna protocol for [153]Sm-EDTMP-therapy is based on the experience of the last two decades. Repeated treatments at a low dose are applied by several authors in order to achieve the maximum therapeutic effect with the lowest haematological toxicity. Significant benefits on pain palliation and some regression are documented. In contrast to earlier claims, [153]Sm-EDTMP treatment should be started as soon as more than 1 bone lesion appears in bone scintigraphy and/or bone pain becomes evident. Prospective randomized controlled studies, however, are urgently warranted in order to assess benefits beyond bone pain palliation on an evidence base. The combination with chemotherapy as well as radiotherapy may further improve the clinical results. Further research should be directed to identify underlying mechanisms of response and predictors of benefit and to elaborate an improved therapeutic schedule for further enhancing the response rate.

Breast carcinoma cell uptake and biodistribution of technetium-99m-carboxymethyl benzylamide dextran.

Carboxymethyl Benzylamide Dextran (CMDB7) displayed an in vitro growth inhibitory activity on breast tumor cells. CMDB7 is able to disrupt the interaction of angiogenic growth factors (FGF2, TGF beta and PDGF) with their membrane receptors. This compound blocks the angiogenesis of MDA-MB435 carcinoma xenografted in mammary fat pad and their lung metastases in nude mice. In this work, we studied the uptake of CMDB7 labeled with 99mTc in cultured human breast cancer MCF-7 cell line and the highly tumorigenic MCF-7ras cell line (Ha-ras-transfected MCF-7 cells) and the in vivo distribution in MCF-7ras tumor-bearing mice. The 99mTc-CMDB7 are stable and the intracellular concentration is time-dependent and reaches a plateau at 180 minutes. 99mTc CMDB7 uptake is much higher in MCF-7ras cells than MCF-7 cells. Since CMDB7 is internalized and could also inhibit cell proliferation by acting at nuclear sites, we investigated the MCF-7ras nuclear localization after cell fractionation. Cell fractionation revealed a cytoplasmic and nuclear internalization of CMDB7. The tumor uptakes of 99mTc-CMDB7 were 0.34%, 0.72% and 0.62% of the administrated doses per gram of tumor tissue at 1 hour, 3 hour and 5 hours respectively after their injection. The blood clearance of 99mTc CMDB7 was very rapid and the liver, spleen and kidney uptakes were very weak. These results confirm the absence of toxicity of CMDB7 and the usefulness of CMDB7 in cancer therapy by targeting breast tumors.

Correlation of technetium-99m MIBI and thallium-201 retention in solitary cold thyroid nodules with postoperative histopathology.

A comparative prospective study of technetium-99m methoxyisobutylisonitrile (MIBI) and thallium-201 with early (15 min) and delayed (90 min for MIBI, 3 h for 201Tl) imaging in the differentiation of thyroid lesions is presented. Forty patients with cold thyroid nodules visualised on 99mTc-pertechnetate scan and with dyskaryotic or atypical epithelial cells verified by fine needle aspiration biopsy underwent MIBI and 201Tl scintigraphy at 3-day intervals. Subsequent thyroidectomies were carried out in all patients. Semiquantitative analysis was performed using a lesion to non-lesion ratio on early (ER) and delayed images (DR). Additionally, a retention index (RI) was calculated using the formula RI=(DR-ER) x 100/ER. The reproducibility of the method for the early and delayed measurements was tested by analysing intra- and inter-observer variability and repeatability coefficients. Histopathologically, the nodules were found to be well-differentiated thyroid cancer in 21 patients and benign in 19 patients. There was no significant difference in the ER between malignant and benign lesions for either 201Tl or MIBI (P>0.05). However, for both agents significant differences were found between malignant and benign lesions with regard to DR (P<0.01 for 201Tl and P<0.001 for MIBI) and RI (P<0.001 for both agents). Statistical comparison of the two agents showed no significant differences (P>0.05) except with regard to DR and RI in malignant nodules (P<0.05). A receiver operating characteristic analysis was performed to determine threshold levels for the differentiation of malignant from benign nodules. Following this analysis, ER, DR and RI levels of 1.03, 1.54 and 2 for MIBI and < or =1.42, 1.24 and 5 for 201Tl were selected. Using these threshold levels, the sensitivity, specificity and accuracy of the study were 90.5%, 36.8% and 65% for ER MIBI, 61.9%, 94.7% and 77.5% for DR MIBI, 95.2%, 89.4% and 92.5% for RI MIBI, 85.7%, 47.3% and 67.5% for ER 201Tl, 80.9%, 73.6% and 77.5% for DR 201Tl, and 90.5%, 94.7% and 92.5% for RI 201Tl. In conclusion, the DR for MIBI and 201Tl is superior to the ER in detecting malignant nodules, and the RI for both MIBI and 201Tl is more valuable than the DR in differentiating malignant from benign thyroid nodules.

Current developments in single photon radiopharmaceuticals for tumor imaging.

Development of peptides and amino acids labeled with single photon gamma emitters has promoted a large number of investigations in nuclear medicine especially for tumor imaging. Radiolabeled peptides have several advantages over antibodies mainly related to immunogenicity and size. Tumor localization and total body clearance of peptides are more rapid compared to antibodies. Recently, several somatostatin analogues labeled with Tc-99m have been studied by several different investigators. In-111 labeled lanreotide (Mauritus) was reported to be highly successful in localization of neuroendocrine tumors. A synthetic amino acid, alpha methyl tyrosine labeled with I-123 was shown to be transported to tumors by a carrier mediated system. Development of a glucose analog labeled with a single photon emitting radionuclide and meeting the structural requirements for hexokinase reaction and phosphorylation have not yet been possible. However, it has been possible to synthesize chemically stable single photon glucose analogues interacting with glut(s), glucose transporters.

Biodistribution of 99Tcm-labelled 5-thio-D-glucose.

We studied the biodistribution and tumour localization of 99Tcm-labelled-5-thio-D-glucose (99Tcm-TG). 5-Thio-D-glucose was labelled with 99Tcm by direct stannous ion reduction. The biodistribution of 99Tcm-TG was investigated in normal rabbits and in mice bearing experimental tumours. In rabbits, the plasma and clearance of 99Tcm-TG was 14.5 +/- 2.0 and 11.3 +/- 3.0 ml.min-1 respectively. Urinary excretion at 1 h was 53 +/- 5%. 99Tcm-TG was injected intravenously in mice bearing MC26 colon carcinoma and tissue samples were analysed by gamma scintillation counting at various times. Uptake of 99Tcm-TG in tumour at 1 and 3 h was 1.6 +/- 0.3% and 1.2 +/- 0.3%; the tumour to muscle ratios were 2.7:1 and 4:1 respectively. The autoradiographic biodistribution of 99Tcm-TG in MX-1 human breast xenografted nude mice showed more persistent tumour uptake of 99Tcm-TG than 14C-2-deoxyglucose (14C-DG). 99Tcm-TG accumulated in the centre of the tumours; 14C-DG was decreased in this central region probably because of zones of infarction on necrosis. The discordance between the tumour uptake of 99Tcm-TG and 14C-DG indicates that 99Tcm-TG does not act like a glucose analog, suggesting 99Tcm-TG avidity for zones of infarction or necrosis. The further study of 99Tcm-TG in tumours and ischaemic injury is warranted.

Preclinical evaluation of benzoporphyrin derivative combined with a light-emitting diode array for photodynamic therapy of brain tumors.

OBJECTIVE: The aim of this study was to investigate the second-generation photosensitizer benzoporphyrin derivative (BPD) and a novel light source applicator based on light-emitting diode (LED) technology for photodynamic therapy (PDT) of brain tumors. METHODS: We used a canine model to investigate normal brain stem toxicity. Twenty-one canines underwent posterior fossa craniectomies followed by PDT with BPD. These animals were compared to light only and BPD control. In addition, we investigated the ability of BPD and LED to cause inhibition of cell growth in canine glioma and human glioma cell lines, in vitro. The biodistribution of BPD labeled with 111In-BPD in mice with subcutaneous and intracerebral gliomas and canines with brain tumors was studied. RESULTS: The in vivo canine study resulted in a maximal tolerated dose of 0.75 mg/kg of BPD and 100 J/cm(2) of LED light for normal brain tissue. The in vitro study demonstrated 50% growth inhibition for canine and human glioma cell lines of 10 and 4 ng/ml, respectively. The mucine study using 111In-BPD showed a tumor to normal tissue ratio of 12:1 for intracerebral tumors and 3.3:1 for subcutaneous tumors. Nuclear scans of canines with brain tumors showed uptake into tumors to be maximal from 3 to 5 h. CONCLUSION: Our study supports that BPD and LED light sources when used at appropriate drug and light doses limit normal brain tissue toxicity at doses that can cause significant glioma cell toxicity in vitro. In addition, there is higher BPD uptake in brain tumors as compared to normal brain in a mouse glioma model. These findings make BPD a potential new-generation photosensitizer for the treatment of childhood posterior fossa tumors as well as other malignant cerebral pathology.

Stop-flow studies of solute uptake in rat lungs.

Stop-flow studies were used to characterize solute uptake in isolated rat lungs. These lungs were perfused at 8 or 34 ml/min for 10-28 s with solutions containing 125I-albumin and two or more of the following diffusible indicators: [3H]mannitol, [14C]urea, 3HOH, 201Tl+, or 86Rb+. After this loading period, flow was stopped for 10-300 s and then resumed to flush out the perfusate that remained in the pulmonary vasculature during the stop interval. Concentrations of 201Tl+ and 86Rb+ in the venous outflow decreased after the stop interval, indicating uptake from exchange vessels during the stop interval. The amount of these K+ analogs lost from the circulation during the stop interval was greater when the intervals were longer. However, losses of 201T1+ at 90 s approached those at 300 s. Because extraction continued after the vasculature had been flushed, vascular levels had presumably fallen to negligible levels during the stop interval. By 90 s of stop flow the vascular volume that was cleared of 201T1+ averaged 0.657 +/- 0.034 (SE) ml in the experiments perfused at 8 ml/min and 0.629 +/- 0.108 ml in those perfused at 34 ml/min. Increases in perfusate K+ decreased the cleared volumes of 201T1+ and 86Rb+. Uptake of [3H]mannitol, [14C]urea, and 3HOH during the stop intervals was observed only when the lungs were loaded at high flow for short intervals. Decreases in 201T1+ and 86Rb+ concentrations in the pulmonary outflow can be used to identify the fraction of the collected samples that were within exchange vessels of the lung during the stop interval and may help determine the distribution of solute and water exchange along the pulmonary vasculature.

Ex vivo anti-CD3 antibody-activated donor T cells have a reduced ability to cause lethal murine graft-versus-host disease but retain their ability to facilitate alloengraftment.

The purpose of this study was to determine whether ex vivo anti-CD3 Ab-activated T cells behaved in a biologically similar manner as naive T cells with respect to causing graft-vs-host disease (GVHD) and facilitating engraftment after allogeneic marrow transplantation. This question was addressed using two well-defined MHC-incompatible murine models of GVHD (C57BL/6 (H-2b)-->BIO.BR (H-2k)) and engraftment (C57BL/6 (H-2b)-->AKR/J (H-2k)). Transplantation with anti-CD3-activated T cells significantly reduced GVHD compared with that in animals transplanted with equivalent numbers of naive T cells. Protection from GVHD was not T cell subset dependent, as highly enriched populations of either activated CD4+ or CD8+ T cells caused less lethal GVHD than comparable numbers of purified naive CD4+ or CD8+ T cells. Transplantation with activated T cells also resulted in protection from LPS-mediated GVH lethality in unirradiated F1 recipients. Analysis of immune recovery indicated that animals transplanted with activated T cells had thymic and splenic B cell reconstitution that compared favorably to that in non-GVHD control mice. When engraftment was analyzed, equivalent degrees of donor cell engraftment were observed when animals were transplanted with limiting numbers (5 x 10(5)) of naive vs activated B6 T cells. Further studies indicated that activated CD8+ T cells were exclusively responsible for enhancing engraftment and that facilitation of engraftment was dependent upon the direct recognition of host MHC alloantigens. Collectively, these data demonstrate that transplantation with anti-CD3 Ab-activated T cells results in a reduction in GVHD, but these cells retain their ability to facilitate alloengraftment. The use of this approach in allogeneic marrow transplantation may represent an alternative strategy to mitigate GVHD without compromising engraftment.

Simplified technetium-99m-EC clearance in adults from a single plasma sample.

UNLABELLED: Technetium-99m-EC has recently been introduced as an alternative renal tubular agent to 131I-ortho iodohippurate (OIH). It has been shown that 99mTc-EC clearance shows strong correlation with OIH clearance and it is possible to estimate effective renal plasma flow. In routine clinical studies, it is practical to use one or two plasma sample methods instead of multiple plasma samples for clearance determination. An attempt was made to determine 99mTc-EC clearance with one sample method. METHODS: Data from 72 subjects were collected. To increase the range of renal function, two anuric hemodialysis patients were also included. Clearances were determined by the open two-compartment model. RESULTS: The clearance range was 12 ml/min to 660 ml/min with a mean of 275 +/- 117 ml/min. Analysis of correlation was made by Tauxe's method. The least standard error of estimation (s.e.e. = 32.71 ml/min) and the best correlation (r = 0.97) between the theoretical volume distribution and the clearance estimations were obtained from the 54-min plasma sample. CONCLUSION: This study suggests that EC clearance could be determined by a simplified single-sample method with an acceptable s.e.e.

Evaluation of 99Tcm-bicisate as a renal imaging agent.

99Tcm-bicisate (99Tcm-ECD), often used as a brain perfusion agent, is rapidly converted following intravenous injection to the polar monoacid (99Tcm-ECM) and diacid (99Tcm-EC) metabolites. Such polar metabolites, which are eliminated principally by renal clearance, are potential renal imaging agents. In this study, 99Tcm-ECD was compared for the first time with 99Tcm-EC, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) and 131I-orthoiodohippurate (OIH) as renal imaging agents in rabbits. Whole-body images and renograms were obtained for all three of the 99Tcm agents, and pharmacokinetic parameters including plasma and urinary clearance were studied for all four agents. The plasma clearance of 99Tcm-EC (37 ml min-1) was slower than that of 99Tcm-ECD (51 ml min-1), which could be accounted for by the higher liver uptake of 99Tcm-ECD. The urinary clearance of 99Tcm-ECD (35 ml min-1), 99Tcm-EC (34 ml min-1) and 99Tcm-MAG3 (39 ml min-1) was similar. The renal images obtained with 99Tcm-ECD were comparable to those for 99Tcm-MAG3 and 99Tcm-EC. However, liver uptake was more prominent with 99Tcm-ECD than with the other agents. The 99Tcm-ECD renogram curves showed a prolonged decrease in renal activity compared to both 99Tcm-EC and 99Tcm-MAG3. In potential human studies, the relatively high liver uptake of 99Tcm-ECD superimposed on right renal activity may be a limitation. Therefore, we conclude that 99Tcm-ECD is less favourable when compared to existing renal agents due to its high extrarenal uptake and renal kinetics.

Evaluation of 99Tc(m)-ECD as a white blood cell labelling agent.

99Tc(m)-ECD is a new agent for perfusion brain imaging. Its brain retention is attributed to the enzymatic conversion of lipophilic 99Tc(m)-ECD to polar monoacid and diacid derivatives. Based on its proposed mechanism of retention in the brain, labelling of white blood cells (WBC) with 99Tc(m)-ECD has been studied at our laboratory. A labelling efficiency of 42% was achieved by incubating WBC with 99Tc(m)-ECD in phosphate buffered saline medium for 30 min. There was a washout of 50% of the radioactivity from the cells in 1 h, which might contribute to increased background in potential human studies. However, rapid urinary elimination of the radioactivity is expected to deal with this problem due to the rapid in vivo conversion of the parent compound to polar metabolites. 99Tc(m)-ECD appears to be a promising agent for labelling WBC. Furthermore, already prepared multidose 99Tc(m)-ECD may be used for either brain perfusion imaging or WBC labelling.

Enterogastric bile reflux during technetium-99m-sestamibi cardiac imaging.

UNLABELLED: Enterogastric bile reflux (EGBR), a risk factor for both gastritis and esophagitis, is a potentially treatable noncoronary cause for chest pain. METHODS: To investigate the frequency of EGBR during different 99mTc-sestamibi cardiac imaging, 1405 consecutive 99mTc-sestamibi SPECT myocardial perfusion studies were reviewed. RESULTS: One hundred sixteen of the 1405 patient studies (8.3%) showed EGBR with roughly equal numbers of patients having marked (43 patients), moderate (38 patients) or minimal (35 patients) intensity of abnormal gastric activity. Two examinations showed gastroesophageal reflux of activity. EGBR was less frequent with treadmill stress testing (5.5% patients) than with pharmacologic stress testing using either dipyridamole (11% of patients) or dobutamine (9.2% of patients) (p > 0.005). EGBR also was more frequent in patients over 40 yr of age. Finally, the prevalence of upper gastrointestinal symptoms and the frequency of established upper gastrointestinal diagnoses correlated strongly with the presence and intensity of EGBR. CONCLUSION: Clarification of the full clinical significance of EGBR during 99mTc-sestamibi cardiac imaging is a topic for future research. Nonetheless, the imaging finding of EGBR may, in fact, identify a potentially treatable noncoronary cause for chest pain.

Technetium-99m sestamibi uptake in human breast carcinoma cell lines displaying glutathione-associated drug-resistance.

An in vitro study was designed to evaluate the uptake of sestamibi (MIBI) in P-glycoprotein (Pgp) and glutathione-associated (GSH) multidrug-resistant (MDR) cell lines. MIBI uptake was studied in various human breast carcinoma cell lines, i.e. in wild-type (MCF7/wt) cells, in adriamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan-resistant (MCF7/mph) cells with increased levels of GSH. The effects of buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells were incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetium-99m MIBI. Both MIBI and 201Tl uptakes were higher for MCF7/mph cells than for the other cells studied. The mean MIBI uptake in MCF7/adr cells was significantly lower than that in MCF7/wt cells (1.9%+/-0.5% vs 3. 1%.0.6%; P <0.01). Verapamil treatment increased the MIBI uptake in MCF7/adr cells (to 2.6%.0.3%; P <0.05). Treatment of MCF7/mph cells with BSO resulted in a significant reduction in GSH content (from 243.2+/-81.1 nmol/mg protein to 17.6+/-4.4 nmol/mg protein; P <0. 001). However, MIBI uptake in BSO-treated and untreated MCF7/mph cells was similar (4.43%+/-0.5% and 5.93%+/-1.7%, respectively; P >0. 1). This study suggests that the uptake of MIBI is not diminished by glutathione-associated drug resistance and that MIBI uptake in a tumour sample does not necessarily indicate that a cancer is sensitive to drugs.

A high-efficiency, rapid and multi-dose procedure for white blood cell labelling with 99Tcm-HMPAO.

99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) is presently recognized as an effective radiopharmaceutical for in vitro white blood cell (WBC) labelling in addition to its widespread utility in cerebral blood flow imaging. While performing clinical studies in patients with a wide range of inflammatory diseases, the effect of the ligand and stannous ion quantity on the labelling efficiency (LE) of WBC was examined. A mean LE of 64 +/- 7% (n = 29) was achieved when the whole HMPAO kit was used for labelling. The LEs were 78 +/- 5% (n = 43), 83 +/- 3% (n = 37) and 85 +/- 5% (n = 18) when one-half, one-third and one-fifth of the lyophilized kit was used, respectively. This is in agreement with the reports of Sampson et al. and Lang et al., suggesting that the optimal formulation of the 99Tcm-HMPAO is a faction of the whole kit. Accordingly, fractionation of a freshly prepared 99Tcm-HMPAO kit into five parts for a high-efficiency WBC labelling is proposed, encouraging the more widespread use of 99Tcm-HMPAO in WBC labelling.

In-111 WBC imaging of osteomyelitis in patients with underlying bone scan abnormalities.

One hundred seven combined In-111 WBC/Tc-99m MDP scans performed on 87 patients with a high clinical suspicion of osteomyelitis were retrospectively reviewed. An 86% sensitivity and a 94% specificity for detecting osteomyelitis were found. In addition, patients were grouped into one of five clinical settings for more detailed analysis: diabetic osteoarthropathy, previous arthroplasty, fracture, overlying skin ulcer, and other etiology. Forty-seven studies were performed while patients received antibiotic therapy without loss of sensitivity for detecting osteomyelitis. Results obtained with scintigraphy compared favorably to other imaging and laboratory studies used to detect osteomyelitis. In conclusion, the combined In-111 WBC/Tc-99m MDP scan is a very sensitive and specific method to detect osteomyelitis in patients with concurrent diabetic osteoarthropathy, fracture, postoperative healing, and overlying skin ulcer. Antibiotic treatment does not appear to adversely affect the sensitivity of these scans.

Evaluation of technetium-99m-ethylenedicysteine in renal disorders and determination of extraction ratio.

UNLABELLED: This article evaluates the clinical usefulness of 99mTc-ethylenedicysteine (EC) in patients with various renal disorders. In addition, extraction ratios of 99mTc-EC in five volunteers were also determined. METHODS: Twenty patients were intravenously injected with 200 MBq 99mTc-EC and 2.5 MBq [131I]orthoiodohippurate (OIH) simultaneously and 11 blood samples were withdrawn within 60 min. Plasma clearance was determined on the basis of a two-compartment model. Imaging was performed in the posterior projection by acquiring three sets of images. Extraction ratios were determined from the blood samples obtained from the renal vein and abdominal aorta. RESULTS: Renal clearance of 99mTc-EC was significantly lower than that of OIH (p = 0.0003) with good correlation (r = 0.93). Volume distributions of 99mTc-EC and OIH were 26584 +/- 10807 ml/1.73 m2 and 23148 +/- 7602 ml/1.73 m2, respectively (p = 0.047). The clearance half-lives of 99mTc-EC and OIH were 98 +/- 54 min and 74 +/- 54 min, respectively (p = 0.049). Protein binding of 99mTc-EC (33 +/- 3.2%) was significantly less than that of OIH (62 +/- 2.8%) (p < 0.0001). Red blood cell binding of 99mTc-EC was almost negligible (5.7 +/- 4.3%). Similar extraction ratios were obtained from blood (0.68 +/- 0.08) and plasma (0.70 +/- 0.07) (p = 0.062). The 60-min excretion fractions were similar for 99mTc-EC and OIH, with values of 50% +/- 20% and 51% +/- 19%, respectively (p = 0.9). CONCLUSION: Technetium-99m-EC is a suitable radiopharmaceutical for routine renal dynamic studies. Although the biological behavior of 99mTc-EC seems to be different from that of OIH, their clearances demonstrate high correlation. Technetium-99m-EC provides excellent quality images and has high potential in the evaluation of quantitative renal functions.

Brain SPECT evaluation of the visual cortex in amblyopia.

UNLABELLED: In amblyopia, the number of visual cortical neurons are reduced and abnormal or absent sensitivity to retinal light stimulation of the amblyopic eye is demonstrated. Ten amblyopic patients were studied to evaluate the response of the visual cortex to visual stimulation. METHODS: All patients with unilateral amblyopia received 500-550 MBq 99mTc-HMPAO during visual stimulation. Strobe light flashing was used as the stimulus for five patients and a checkerboard pattern reversal was used in the other five patients, closing one eye. For both groups a 2-Hz frequency was used. One week later, the same procedure was repeated with the opposite eye closed. SPECT images were reconstructed with prefiltering techniques and sliced along the orbitomeatal line. RESULTS: For all patients, the amblyopic eye demonstrated less radioactivity in the visual cortex than in the normal eye. The mean cerebral-to-cerebellar ratios were 0.95 +/- 0.05 and 1.09 +/- 0.07 for amblyopic and normal eyes, respectively (p < 0.0001). CONCLUSION: Visual cortex response of the amblyopic eye to light stimulation was severely reduced when compared to the normal eye.

Clinical comparison of technetium-99m-EC, technetium-99m-MAG3 and iodine-131-OIH in renal disorders.

UNLABELLED: Technetium-99m-ethylenedicysteine has recently been developed for renal function studies. The pharmacokinetics of 99mTc-EC were studied by constant infusion technique and compared with 99mTc-MAG3 and 131I-OIH in 11 patients with various renal disorders. METHODS: After giving a 7.4 MBq 131I-OIH and 90-110 MBq 99mTc-EC or 99mTc-MAG3 bolus, a constant infusion (1MBq/ml 99mTc-agent and 0.07 MBq/m 131I-OIH was started. Sixteen blood and five urine samples were obtained over three hr. RESULTS: The renal clearance of 99mTc-EC was higher than that of 99mTc-MAG3. The 99mTc-EC/OIH and 99mTc-MAG3/OIH ratios were 0.75 +/- 0.05 and 0.55 +/- 0.10 (p = 0.00087), respectively. The distribution volume of 99mTc-EC was also higher than that of 99mTc-MAG3 (15722 +/- 4644 and 9509 +/- 2788 ml/1.73m2, respectively; p = 0.072). The 99mTc-EC/OIH and 99mTc-MAG3/OIH distribution volume ratios were 1.03 +/- 0.14 and 0.55 +/- 0.10, respectively (p = 0.0003). The 60-min excretion values of 99mTc-EC and 99mTc-MAG3 were compared to that of OIH. The 99mTc-EC/OIH and 99mTc-MAG3/OIH excretion ratios were 0.96 +/- 0.06 and 1.07 +/- 0.10, respectively (p = 0.162). The protein binding of 99mTc-EC and OIH were found to be 34% +/- 4 and 66% +/- 5, respectively (p < 0.0001). The red cell binding of 99mTc-EC was negligible (3% +/- 1.2) in comparison to OIH (27% +/- 3; p < 0.0001). CONCLUSION: This limited study demonstrates the pharmacokinetic and renal clearance properties of 99mTc-EC. This agent has good potential for renal function evaluation.

Phosphorus-32-chromic phosphate for ovarian cancer: I. Fractionated low-dose intraperitoneal treatments in conjunction with platinum analog chemotherapy.

UNLABELLED: For many years, 32P-chromic phosphate (32P-CP) intraperitoneal instillations and platinum analogue chemotherapy have been used to treat disseminated ovarian cancer. To investigate possible enhancement of 32P-CP irradiation due to the concomitant administration of chemotherapy, in vitro studies were undertaken. Based on those laboratory investigations, a clinical regimen of combined 32P-CP and platinum analogue chemotherapy was developed. METHODS: In vitro enhancement of 32P-CP cytotoxicity by cisplatin was studied in cultured human ovarian adenocarcinoma (CHOA) cell lines and in a fibroblast cell strain. In addition, ovarian cancer cells obtained from the malignant abdominal ascites and pleural effusions of 10 individual patients were also studied ex vivo. As part of routine clinical care, 30 patients with disseminated ovarian adenocarcinoma underwent up to eight monthly cycles of platinum analogue chemotherapy with concomitant intraperitoneal instillation of 5 mCi of 32P-CP at each monthly chemotherapy cycle. RESULTS: There was an enhanced and possibly supra-additive effect of cisplatin on the cytotoxicity from 32P-CP irradiation. For the 30 patients, the survival rate at 3 yr was 63%. CONCLUSION: Phosphorus-32 CP low-dose intraperitoneal treatments in conjunction with platinum analogue chemotherapy is a promising approach for the treatment of disseminated intraperitoneal ovarian cancer.