Can positron emission tomography improve the quality of care for head-and-neck cancer patients?

PURPOSE: Fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is a functional imaging modality that measures the relative uptake of 18FDG with PET. The purpose of this review is to assess the potential contribution of FDG-PET scans to the treatment of head-and-neck cancer patients. METHODS AND MATERIALS: Data were assessed from the literature with attention to what additional information may be gained from the use of FDG-PET in four clinical settings: (1) detection of occult metastatic disease in the neck, (2) detection of occult primaries in patients with neck metastases, (3) detection of synchronous primaries or metastatic disease in the chest, and (4) detection of residual/recurrent locoregional disease. RESULTS: Although the data are somewhat conflicting, FDG-PET appears to add little additional value to the physical examination and conventional imaging studies (supplemented by biopsy when appropriate) for the detection of subclinical nodal metastases, unknown primaries, or disease in the chest. However, FDG-PET scans are quite useful in differentiating residual/recurrent disease from treatment-induced normal tissue changes. A positive FDG-PET scan at 1 month after radiotherapy is highly indicative of the presence of residual disease, and a negative scan at 4 months after treatment is highly predictive of tumor eradication. CONCLUSIONS: Large-scale studies using newer generation equipment and more defined methods are needed to more rigorously assess the potential of FDG-PET in the detection of subclinical primary or simultaneous secondary tumors and of nodal or systemic spread. Currently, however, FDG-PET can contribute to the detection of residual/early recurrent tumors, leading to the timely institution of salvage therapy or the prevention of unnecessary biopsies of irradiated tissues, which may aggravate injury.

Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.

In vivo and in vitro measurement of apoptosis in breast cancer cells using 99mTc-EC-annexin V.

OBJECTIVE: The purpose of this study was to develop an imaging technique to measure and monitor tumor cells undergoing programmed death caused by radiation and chemotherapy using 99mTc-EC-annexin V. Annexin V has been used to measure programmed cell death both in vitro and in vivo. Assessment of apoptosis would be useful to evaluate the efficacy and mechanisms of therapy and disease progression or regression. METHODS: Ethylenedicysteine (EC) was conjugated to annexin V using sulfo-N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-HCl as coupling agents. The yield of EC-annexin V was 100%. In vitro cellular uptake, pre- and post-radiation (10-30 Gy) and paclitaxel treatment, was quantified using 99mTc-EC-annexin V. Tissue distribution and planar imaging of 99mTc-EC-annexin V were determined in breast tumor-bearing rats at 0.5, 2, and 4 hrs. To demonstrate in vivo cell apoptosis that occurred during chemotherapy, a group of rats was treated with paclitaxel and planar imaging studies were conducted at 0.5-4 hrs. Computer outlined region of interest (ROI) was used to quantify tumor uptake on day 3 and day 5 post-treatment. RESULTS: In vitro cellular uptake showed that there was significantly increased uptake of 99mTc-EC-annexin V after irradiation (10-30 Gy) and paclitaxel treatment. In vivo biodistribution of 99mTc-EC-annexin in breast tumor-bearing rats showed increased tumor-to-blood, tumor-to-lung and tumor-to-muscle count density ratios as a function of time. Conversely, tumor-to-blood count density ratios showed a time-dependent decrease with 99mTc-EC in the same time period. Planar images confirmed that the tumors could be visualized clearly with 99mTc-EC-annexin. There was a significant difference of ROI ratios between pre- and post-paclitaxel treatment groups at 2 and 4 hrs post injection. CONCLUSION: The results indicate that apoptosis can be quantified using 99mTc-EC-annexin and that it is feasible to use 99mTc-EC-annexin to image tumor apoptosis.

Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial.

BACKGROUND: Prostate carcinoma is linked to osteoblastic metastasis. We therefore investigated the value of bone-targeted consolidation therapy in selected patients with advanced androgen-independent carcinoma of the prostate. METHODS: 103 patients received induction chemotherapy, consisting of ketoconazole and doxorubicin alternating with estramustine and vinblastine. After two or three cycles of induction chemotherapy, we randomly assigned 72 patients who were clinically stable or responders to receive doxorubicin with or without strontium-89 (Sr-89) every week for 6 weeks. FINDINGS: Overall 62 of the 103 (60%, 95% CI 50-70) patients had a 50% or greater reduction in serum prostate-specific antigen concentration that was maintained for at least 8 weeks, and 43 (42%, 32-52) had an 80% or greater reduction. 49 (52%) patients with bone pain at registration had complete resolution of pain. After follow-up of 67 patients until death, the estimated median survival for all 103 patients was 17.5 months (range 0.5-37.7). For the 36 patients randomly assigned to receive Sr-89 and doxorubicin, the median survival time was 27.7 months (4.9-37.7), and for the 36 who received doxorubicin alone it was 16.8 months (4.4-34.2) (p=0.0014). The hazard ratio was 2.76 (95% CI 1.44-5.29). INTERPRETATION: Bone-targeted consolidation therapy consisting of one dose of Sr-89 plus doxorubicin once a week for 6 weeks, when given to patients with stable or responding advanced androgen-independent carcinoma of the prostate after induction chemotherapy, improved overall survival.

Determination of glomerular filtration rate using a dual-detector gamma camera and the geometric mean of renal activity: correlation with the Tc-99m DTPA plasma clearance method.

PURPOSE: In this study, the authors studied the use of a dual-detector gamma camera to measure the glomerular filtration rate (GFR). METHODS: Thirty-three patients with a wide range of renal function participated in this study. The GFR was measured using a dual-detector gamma camera by calculating the geometric mean of activity from each kidney and using an outline background. These results were compared with the GFR estimates obtained from Tc-99m DTPA plasma clearance using a multiple blood sample method. RESULTS: Correlation was excellent between GFR estimated using the dual-detector gamma camera and GFR measured using the plasma clearance of Tc-99m DTPA with multiple blood samples (r = 0.89). The correlation was especially strong in children younger than 13 years (r = 0.94). CONCLUSION: Measuring the GFR using a dual-detector gamma camera and calculating the geometric mean of renal activity yields relatively accurate results.

Assessment of resistance to paclitaxel of murine tumors by (99m)Tc-MIBI/(201)Tl dual-radionuclide imaging.

This study investigated P-glycoprotein (Pgp) expression by murine tumors with and without resistance to paclitaxel and the role of (99m)Tc-2-methoxyisobutylisonitrile (MIBI)/(201)Tl imaging in predicting the effect of paclitaxel. Antitumor effect of paclitaxel and biodistribution of the radiopharmaceuticals were evaluated in mice bearing four tumor types. Pgp expression did not correlate with the antitumor efficacy of paclitaxel. Although the absolute uptake of (99m)Tc-MIBI did not correlate with Pgp expression, (99m)Tc-MIBI could predict paclitaxel sensitivity by its higher uptake.

Synthesis of [99mTc]ethylenedicysteine-colchicine for evaluation of antiangiogenic effect.

Angiogenesis is in part responsible for tumor growth and the development of metastasis. Radiolabeled angiongenesis inhibitors would be useful to assess tumor microvasculature density. Colchicine (COL), a potent antiangiogenic agent, is known to inhibit microtubule polymerization and cell arrest at metaphase. This study aimed to develop 99mTc-labeled COL (EC-COL) using ethylenedicysteine (EC) as a chelator to assess tumor microvascular density. EC was conjugated to trimethylcolchicinic acid using N-hydroxysuccinimide and 1-ethyl-3-dimethylaminopropyl carbodiimide as coupling agents with a yield of 50-60%. In vivo stability was analyzed in rabbit serum at 0.5-4 h. Tissue distribution and planar imaging studies of [99mTc]EC-COL were evaluated in breast tumor-bearing rats at 0.5, 2 and 4 h. The data was compared to that using [99mTc]EC (control). The radiochemical yield of [99mTc]EC-COL was greater than 95%. [99mTc]EC-COL was stable in rabbit serum. In vivo biodistribution of [99mTc]EC-COL in breast tumor-bearing rats showed increased tumor-to-blood (0.52+/-0.12 to 0.72+/-0.07) and tumor-to-muscle (3.47+/-0.40 to 7.97+/-0.93) ratios as a function of time. Conversely, tumor-to-blood values showed a time-dependent decrease with [99mTc]EC over the same time period. Planar images confirmed that the tumors could be visualized clearly with [99mTc]EC-COL from 0.5 to 4 h. [99mTc]EC-COL may be useful to assess antiangiogenic and therapeutic effects during chemotherapy.

Evaluation of In-111 DTPA-paclitaxel scintigraphy to predict response on murine tumors to paclitaxel.

UNLABELLED: Our goal was to determine whether scintigraphy with 111In-DTPA-paclitaxel could predict the response to chemotherapy with paclitaxel. METHODS: Ovarian carcinoma (OCA 1), mammary carcinoma (MCA-4), fibrosarcoma (FSA) and squamous cell carcinoma (SCC VII) were inoculated into the thighs of female C3Hf/Kam mice. Mice bearing 8 mm tumors were treated with paclitaxel (40 mg/kg). The growth delay, which was defined as the time in days for tumors in the treated groups to grow from 8 to 12 mm in diameter minus the time in days for tumors in the untreated control group to reach the same size, was measured to determine the effect of paclitaxel on the tumors. Sequential scintigraphy in mice bearing 10 to 14 mm tumors was conducted at 5, 30, 60, 120, 240 min and 24 hrs postinjection of 111In-DTPA-paclitaxel (3.7MBq) or 111In-DTPA as a control tracer. The tumor uptakes (% injection dose/pixel) were determined. RESULTS: The growth delay of OCA 1, MCA-4, FSA and SCC VII tumors was 13.6, 4.0, -0.02 and -0.28 days, respectively. In other words, OCa 1 and MCA-4 were paclitaxel-sensitive tumors, whereas FSA and SCC VII were paclitaxel-resistant tumors. The tumor uptakes at 24 hrs postinjection of In-111 DTPA paclitaxel of OCA 1, MCA-4, FSA and SCC VII were 1.0 x 10(-3), 1.6 x 10(-3), 2.2 x 10(-3) and 9.0 x 10(-3) % injection dose/pixel, respectively. There was no correlation between the response to chemotherapy with paclitaxel and the tumor uptakes of 111In-DTPA-paclitaxel. CONCLUSIONS: Scintigraphy with 111In-DTPA-paclitaxel could not predict the response to paclitaxel chemotherapy. Although there was significant accumulation of the paclitaxel in the tumor cells, additional mechanisms must be operative for the agent to be effective against the neoplasm. 111In-DTPA-paclitaxel activity is apparently different from that of paclitaxel with Cremophor.

Noninvasive assessment of tumor hypoxia with 99mTc labeled metronidazole.

PURPOSE: The assessment of tumor hypoxia by imaging modality prior to radiation therapy would provide a rational means of selecting patients for treatment with radiosensitizers or bioreductive drugs. This study aimed to develop a 99mTc-labeled metronidazole (MN) using ethylene-dicysteine (EC) as a chelator and evaluate its potential use to image tumor hypoxia. METHODS: EC was conjugated to amino analogue of MN using Sulfo-N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-HCl as coupling agents, the yield was 55%. Tissue distribution of 99mTc-EC-MN was determined in breast tumor-bearing rats at 0.5, 2, and 4 hrs. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using 99mTc-EC (control), [18F]fluoromisonidazole (FMISO) and [(131)I] iodomisonidazole (IMISO). RESULTS: In vivo biodistribution of 9mTc-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to-muscle ratios as a function of time. Conversely, tumor-to-blood values showed time-dependent decrease with 9mTc-EC in the same time period. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with 99mTc-EC-MN from 0.5 to 4 hrs. There was no significant difference of tumor-to-blood count ratios between 99mTc-EC-MN and [(131)I]IMISO at 2 and 4 hrs postinjection. From 0.5 to 4 hrs, both 9mTc-EC-MN and [(131)I]MISO have higher tumor-to-muscle ratios compared to [18]FMISO. CONCLUSIONS: It is feasible to use 9mTc-EC-MN to image tumor hypoxia.

Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor-bearing rats.

The aim of this study was to develop an 111In-labeled diethylenetriamine pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adriamycin with DTPA anhydride in the presence of carbonyldiimidazole. After dialysis (MW cut off was 500), the product was freeze-dried (yield 40-50%). An in vitro cell culture study was performed using cells from the 13,762 Fischer rat mammary tumor line. Drug concentrations tested were 0.1-100 microM. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time interval, 10 microCi/rat, i.v.) with 13,762 cells (10(5) cells/rat, s.c.). Planar imaging and autoradiograms were obtained at the same intervals. In vitro cell culture assays showed an IC50 of 0.1 +/- 0.01 microM for ADR and 7.2 +/- 0.29 microM for DTPA-ADR, respectively. In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5, 2, 24 and 48 h were 0.55 +/- 0.17, 0.94 +/- 0.17, 3.06 +/- 0.53 and 3.66 +/- 0.35, respectively, whereas those for [111In]DTPA (control) were 1.19 +/- 0.69, 0.84 +/- 0.07, 0.56 +/- 0.10 and 0.60 +/- 0.03, respectively. The tumor uptake value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and autoradiograms showed good visability of tumors. Biodistribution, autoradiography and radionuclide imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h. These results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in the diagnosis of breast cancer and may predict a therapeutic effect prior to treatment.

Role of indium-111 labelled platelet scintigraphy in the management of thrombocytopenic patients with malignant neoplasms.

This study was done to investigate the role of indium-111 labelled platelet scintigraphy in the treatment of thrombocytopenia in patients with malignant neoplasms. The study involved 20 consecutive patients with thrombocytopenia associated with malignant neoplasms of hematological disorders and without evidence of underproduction of megakaryocytes due to chemotherapy or bone marrow infiltration by the malignancy. Splenic sequestration of platelets was evaluated by measuring splenic uptake of 111In-labelled platelets, and findings were correlated with the outcome of splenectomy and medication. Of the 20 patients, 13 had splenic sequestration of platelets. Seven of the 13 patients underwent splenectomy; six of these seven patients experienced a complete response. The other six patients received medication only and showed no response. Of the seven patients without splenic sequestration of platelets, five received medication, and four of them responded to it. 111In-labelled platelet scintigraphy has a role in selecting appropriate therapy and predicting its efficacy in patients with thrombocytopenia associated with malignant neoplasms.

Imaging tumor folate receptors using 111In-DTPA-methotrexate.

It is known that membrane folic acid receptors are responsible for cellular accumulation of folate and folate analogs, such as methotrexate, and overexpressed on various tumor cells. This study was aimed to develop an 111In labelled DTPA-methotrexate (DTPA-MTX) to image tumor folate receptors in vivo. DTPA-MTX was synthesized by reacting ethylenediamine with MTX. The resulting amino analogue of MTX was reacted with DTPA dianhydride in basic aqueous solution followed by dialysis. Tissue distribution was determined in breast tumor-bearing rats at 0.5, 2, 24, and 48 h (n = 3/time interval). To determine receptor-mediated process 111In-DTPA-MTX was co-administrated with varying blocking doses of cold folate to tumor-bearing rats. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using 111In-DTPA. In animal studies, tumor/blood count density ratios at 0.5-48 h gradually increased from 0.8 +/- 0.32 to 2.2 +/- 0.41 with 111In-DTPA-MTX. Conversely, these values showed time-dependent decrease from 1.19 +/- 0.69 to 0.56 +/- 0.10 with 111In-DTPA in the same time period. Tumor/muscle and tumor/blood count density ratios significantly decreased with high doses of folic acid co-administration. Planar images and autoradiograms confirmed that the tumors could be visualized acceptably with 111In-DTPA-MTX. The results indicate the feasibility of using 111In-DTPA-MTX to image tumors through a folate receptor-mediated process.

99mTc-ethylenedicysteine-folate: a new tumor imaging agent. Synthesis, labeling and evaluation in animals.

It is known that membrane folic acid receptors are responsible for cellular accumulation of folate and folate analogs such as methotrexate and overexpressed on various tumor cells. However, these receptors are highly restricted in normal differentiated tissues. Results of limited in vitro and in vivo animal studies suggest that folate receptors could be a potential target for tumor imaging. This study aimed to develop a 99mTc-labeled folic acid using ethylenedicysteine (EC) as a chelator and evaluate its labeling efficiency and potential use as a tumor seeking agent. Tissue distribution of 99mTc-EC-folate was determined in breast tumor-bearing rats at 20 min, 1, 2, and 4 h (n = 3/time interval, 370 KBq/rat, i.v.). Blocking study was employed to determine receptor-mediated process; 99mTc-EC-folate was co-administrated with 50 and 150 mumol/kg of cold folic acid to tumor-bearing rats. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using 99mTc-EC (control). In animal studies, tumor/blood count density ratios at 20 min-4 h increased from 0.81 +/- 0.09 to 1.23 +/- 0.13 with 99mTc-EC-folate. Conversely, these values showed time-dependent decrease from 0.77 +/- 0.32 to 0.65 +/- 0.01 with 99mTc-EC in the same time period. Tumor/muscle and tumor/blood count density ratios significantly decreased with folic acid co-administrations. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with 99mTc-EC-folate.

Preliminary study of cardiac accumulation of F-18 fluorotamoxifen in patients with breast cancer.

The clinical meaning of cardiac uptake of [18F]fluorotamoxifen was assessed. Tamoxifen, a nonsteroidal antiestrogenic drug for treatment and prevention of breast cancer, has a cardioprotective, estrogen-like effect in postmenopausal women. We conducted a pilot study of [18F]fluorotamoxifen to evaluate its clinical usefulness in patients with breast cancer. Significant cardiac uptake of [18F]fluorotamoxifen in five patients was found in the pilot study. We performed positron emission tomography (PET) with [18F]fluorotamoxifen. The intracardiac distribution of [18F]fluorotamoxifen was observed and compared with the patients' clinical symptoms, past history, and results of the electrocardiogram (ECG). None of the patients had a prior history of ischemic heart disease. Various patterns of [18F]fluorotamoxifen distribution were seen in the heart: one patient showed homogeneous distribution; two had defects in the lateral wall; one had patchy distribution; and in one the uptake was questionable. Non-uniform cardiac uptake may be related to myocardial damage. Cardiac uptake of tamoxifen suggests that its cardioprotective benefits may be related not only to serum cholesterol reduction but also to a direct cardioprotective action. Further experimental studies are required to elucidate the pathophysiological mechanism of cardiac uptake of [18F]fluorotamoxifen.

Correlation between bone scan findings and collagenase activities in patients with breast cancer.

RATIONALE AND OBJECTIVES: This study correlates nuclear bone scan findings and measurements of type IV collagenases for the evaluation of bony metastasis in patients with proven breast cancer. METHODS: The authors retrospectively evaluated the final diagnosis of a bone scan and the results of an immunohistochemical staining for 92 kDa and 72 kDa type IV collagenases in, respectively, 30 and 30 patients with metastatic breast cancer, and, respectively, 27 and 26 patients with primary breast cancer. The immunohistochemical staining was performed with tissue specimens obtained from a primary or metastatic breast tumor lesion. The amounts of the enzyme were graded from 0 to 4 and scored by multiplication with the percentage of tumor cells. The confidence of bone scan interpretation also was scored from 1 to 5 with increasing probability. RESULTS: There was a significant difference in enzyme scores between patients with and without metastases. Patients with < 170 92 kDa (26 of 27), 72 kDa (26 of 26) type IV collagenase, showed no active bony, lung, or liver metastases. However, there were variable bone scan findings in patients with a > 200 enzyme score. CONCLUSIONS: Bone scan provides no additional benefit in breast cancer patients with a type IV collagenase score of < 170. A bone scan is necessary to confirm, localize, or followup bony metastases in patients with an enzyme score of > 200.

Effect of recombinant alpha-interferon on pharmacokinetics, biodistribution, toxicity, and efficacy of 131I-labeled monoclonal antibody CC49 in breast cancer: a phase II trial.

Preclinical studies have demonstrated that recombinant IFN-alpha (rIFN-alpha) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors. To determine whether rIFN-alpha could enhance TAG-72 expression in vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-alpha (3 x 10(6) units/m2 for 14 days) beginning on day 1 (group 1 = 7 patients) or on day 6 (group 2 = 8 patients). On day 3, all patients received a 10-20-mCi tracer dose of 131I-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m2 of 131I-CC49 on day 6. Whole body and single-photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases. Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients. Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment. For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 +/- 4.7 versus 51.5 +/- 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 +/- 0.35 versus 1. 07 +/- 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-alpha was found to enhance TAG-72 expression in tumors from patients receiving rIFN-alpha (group 1) by 46 +/- 19% (P < 0.05) compared to only 1.3 +/- 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-alpha-treated patients. One partial and two minor tumor responses were seen. In summary, rIFN-alpha treatment altered the pharmacokinetics and tumor uptake of 131I-CC49 in patients at the expense of increased toxicity.

Evaluation of [131I]iodoerythronitroimidazole as a predictor for the radiosensitizing effect.

The aim of this study was to evaluate whether radiolabeled iodoerythronitroimidazole (IETNIM) could predict the radiosensitization effect on tumors. Tumor-bearing mice were irradiated at a dose of 25, 31 and 37 Gy after the injection of IETNIM. They were also exposed to 37 Gy radiation at 35, 70, 140 and 240 min after the i.p. injection of IETNIM. After the irradiation, tumor growth assays were conducted and the effect of IETNIM as a radiosensitizer was estimated as enhancement factor (EF). Tumor uptake was measured at 35, 70, 140 and 240 min after i.p. injection of [131I]IETNIM, which were the same intervals used in the radiosensitization study. EF of IETNIM in mice treated with 25, 30 and 37 Gy irradiation was 0.72, 0.98 and 1.28, respectively. EF of IETNIM in mice irradiated at 35, 70, 140 and 240 min after the injection was 1.50, 1.69, 1.46 and 1.08, which corresponded to the tumor uptake and blood clearance of [131I]IETNIM. [131I]IETNIM may be a suitable radiopharmaceutical to predict the radiosensitization effect of misonidazole analogs on tumors.

Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine PET in detection of malignant tumors.

UNLABELLED: Two commonly used tumor-seeking agents for PET are 2-deoxy-2-18F-fluoro-D-glucose (FDG) and L-methyl-11C-methionine (Met). This study compared FDG and Met in detecting residual or recurrent malignant tumors in the same patients. METHODS: Thirty-four lesions in 24 patients with clinically suspected recurrent or residual tumors were studied with PET using Met as well as FDG. FDG scans were conducted 1 hr after the completion of PET with Met. The color-coded superimposed images of standardized uptake values (SUVs) and transmission data were produced, and the peak SUVs in the lesions were then evaluated. Lesions above 2.5 SUV were interpreted as positive results for active tumor. RESULTS: The sensitivity of FDG-PET and Met-PET were 64.5% (20/31 lesions) and 61.3% (19/31 lesions), respectively. The mean SUV of FDG in residual or recurrent malignant tumors (n = 31) was significantly higher than that of Met but there was a significant correlation (r = 0.788, p < 0.01) between FDG and Met SUVs in all lesions (n = 34). CONCLUSION: PET using FDG and Met appear equally effective in detecting residual or recurrent malignant tumors although FDG uptakes were slightly higher than Met uptakes. Both showed a limited diagnostic sensitivity for small (< 1.5 cm) tumors.