Kinetic analysis and optimisation of 18F-rhPSMA-7.3 PET imaging of prostate cancer.

PURPOSE: This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, 18F-rhPSMA-7.3, to optimise its use for imaging of prostate cancer. METHODS: Nine men, three with high-risk localised prostate cancer, three with treatment-naïve hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq 18F-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35-45, 60-88 and 90-118 min. Net influx rates (Ki) were calculated using Patlak plots. RESULTS: Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The 18F-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. Ki, SUV and lesion-to-reference ratio estimates showed good agreement. CONCLUSION: 18F-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, 18F-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer. TRIAL REGISTRATION: NCT03995888 (24 June 2019).

Quantitative and Qualitative Assessment of Urinary Activity of 18F-Flotufolastat-PET/CT in Patients with Prostate Cancer: a Post Hoc Analysis of the LIGHTHOUSE and SPOTLIGHT Studies.

PURPOSE: To evaluate the impact of urinary activity on interpretation of 18F-flotufolastat (18F-rhPSMA-7.3) PET/CT, we conducted a post hoc qualitative and quantitative analysis of scans acquired in two phase 3 studies of 18F-flotufolastat. PROCEDURES: Newly diagnosed or recurrent prostate cancer patients enrolled in LIGHTHOUSE (NCT04186819) or SPOTLIGHT (NCT04186845), respectively, underwent PET/CT 50-70 min after intravenous administration of 296 MBq 18F-flotufolastat. For the present analysis, 718 18F-flotufolastat scans (352 from LIGHTHOUSE and 366 from SPOTLIGHT) were re-evaluated by three board-certified nuclear medicine physicians. Reader 1 performed a quantitative assessment (SUVmax and SUVmean) of bladder activity in a circular region-of-interest over the maximum diameter of bladder activity in the transverse plane. All three readers qualitatively assessed the impact of any urinary activity in the bladder on image interpretation using a three-point scale (0 = no/minimal visible urinary activity, 1 = urinary activity visible but distinction between urine and disease possible and 2 = assessment inhibited by urinary activity) and the presence/absence of ureteric activity and halo artifacts. RESULTS: In total, 712/718 scans were evaluable. Reasons for exclusion were cystectomy, renal failure, or urinary catheter in situ (n = 2 each). The median bladder SUVmax and SUVmean were 17.1 and 12.5, respectively. By majority read, 682/712 (96%) patients had either no urinary activity (score = 0) or visible activity that could be distinguished from disease uptake (score = 1). In the minority of patients (24, 3.4%) where urinary activity did impact assessment (score = 2), the median bladder SUVmean was higher (20.5) than those scored 0 (3.8) or 1 (14.0). Ureteric activity was absent in 401 (56%) patients. Halo artifacts were observed in only two (0.3%) patients (majority read). CONCLUSIONS: 18F-Flotufolastat urinary activity did not influence disease assessment for the majority of patients. While this study was not designed as a head-to-head comparison, the median bladder SUVs are lower than previously reported values for other renally cleared PSMA-PET radiopharmaceuticals.

Uptake of 18F-rhPSMA-7.3 in Positron Emission Tomography Imaging of Prostate Cancer: A Phase 1 Proof-of-Concept Study.

Background: This study evaluated tracer uptake and lesion detectability with the novel radiopharmaceutical 18F-radiohybrid (rh)PSMA-7.3 in patients with prostate cancer (PCa). Materials and Methods: Ten patients (three with high-risk primary localized PCa [Cohort A], three with hormone-sensitive metastatic PCa [Cohort B], and four with castration-resistant metastatic PCa [Cohort C]) underwent whole-body 18F-rhPSMA-7.3 positron emission tomography (PET)/computed tomography (CT) and findings were correlated with standard-of-care imaging. 18F-rhPSMA-7.3 maximum standardized uptake value (SUVmax) and its possible association with Gleason score (GS)/International Society of Urological Pathology (ISUP) grade group (GG) and serum PSA levels were evaluated. Cohort A 18F-rhPSMA-7.3 findings were also correlated with histopathology, including prostate-specific membrane antigen (PSMA) staining. Results: 18F-rhPSMA-7.3 identified the primary tumor in 3/3 Cohort A patients and lymph node (LN) and/or bone lesions in 7/7 metastatic patients. All prostate lesions with GS ≥4 + 3/GG ≥3 were identified, but only 1/4 GS ≤3 + 4/GG ≤2 lesions. Prostate lesion SUVmax appeared positively associated with GS/GGs. Among metastatic patients, 18F-rhPSMA-7.3 identified all known pelvic and extrapelvic LN metastases and all known bone lesions. 18F-rhPSMA-7.3 detected possible additional nodal and bone lesions not reported in standard-of-care imaging in all metastatic patients. No association existed between bone or LN uptake and either GS/GG or PSA. Conclusions: 18F-rhPSMA-7.3 PET/CT showed good detection of primary and metastatic PCa lesions. In this small patient population, 18F-rhPSMA-7.3 identified intraprostatic lesions with GS ≥4 + 3/GG ≥3 with good accuracy.

Safety, Biodistribution, and Radiation Dosimetry of 18F-rhPSMA-7.3 in Healthy Adult Volunteers.

This first-in-humans study investigated the safety, biodistribution, and radiation dosimetry of a novel 18F-labeled radiohybrid prostate-specific membrane antigen (rhPSMA) PET imaging agent, 18F-rhPSMA-7.3. Methods: Six healthy volunteers (3 men, 3 women) underwent multiple whole-body PET acquisitions at scheduled time points up to 248 min after the administration of 18F-rhPSMA-7.3 (mean activity, 220; range, 210-228 MBq). PET scans were conducted in 3 separate sessions, and subjects were encouraged to void between sessions. Blood and urine samples were collected for up to 4 h after injection to assess metabolite-corrected radioactivity in whole blood, plasma, and urine. Quantitative measurements of 18F radioactivity in volumes of interest over target organs were determined directly from the PET images at 8 time points, and normalized time-activity concentration curves were generated. These normalized cumulated activities were then inputted into the OLINDA/EXM package to calculate the internal radiation dosimetry and the subjects' effective dose. Results:18F-rhPSMA-7.3 was well tolerated. One adverse event (mild headache, not requiring medication) was considered possibly related to 18F-rhPSMA-7.3. The calculated effective dose was 0.0141 mSv/MBq when using a 3.5-h voiding interval. The organs with the highest mean absorbed dose per unit of administered radioactivity were the adrenals (0.1835 mSv/MBq), the kidneys (0.1722 mSv/MBq), the submandibular glands (0.1479 mSv), and the parotid glands (0.1137 mSv/MBq). At the end of the first scanning session (mean time, 111 min after injection), an average of 7.2% (range, 4.4%-9.0%) of the injected radioactivity of 18F-rhPSMA-7.3 was excreted into urine. Conclusion: The safety, biodistribution, and internal radiation dosimetry of 18F-rhPSMA-7.3 are considered favorable for PET imaging.

Initial results of hypoxia imaging using 1-alpha-D: -(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole ( 18F-FAZA).

PURPOSE: Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-alpha-D: -(5-deoxy-5-[(18)F]-fluoroarabinofuranosyl)-2-nitroimidazole ((18)F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. METHODS: Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of (18)F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal (18)F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. RESULTS: Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of (18)F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of (18)F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased (18)F-FAZA uptake in the primary lung tumour. No side effects of the administration of (18)F-FAZA were observed. CONCLUSION: This study suggests that (18)F-FAZA may be a very useful radiopharmaceutical to image hypoxia in the tumour types selected. Especially the high uptake by gliomas was encouraging. Given the good imaging properties, including acceptable T/B ratios in the tumour categories studied, (18)F-FAZA could be considered as a very promising agent for assessing the hypoxic fraction of these tumour types.

FDG-PET in the clinically negative neck in oral squamous cell carcinoma.

OBJECTIVE: With improved diagnostic imaging techniques, it remains difficult to reduce occult metastatic disease in oral squamous cell carcinoma (SCC) to less than 20%. Therefore, supraomohyoid neck dissection (SOHND) still is a valuable staging procedure in these patients. METHODS: Patients with clinically and ultrasonographically staged cN0 SCC of the oral cavity underwent FDG-PET before SOHND. Histologic examination of neck dissection specimens was used as a "gold standard." RESULTS: Twenty-eight consecutive patients were included, representing 30 necks. Occult metastatic disease was found in 30% of SOHND specimens. Average diameter of metastatic deposits was 4.3 mm. Sensitivity, specificity, and accuracy of FDG-PET was 33%, 76%, and 63%, respectively. CONCLUSIONS: In patients with cN0 SCC of the oral cavity, FDG-PET does not contribute to the preoperative workup. FDG-PET does not replace SOHND as a staging procedure.

Targeting of biliary cancer with radiolabeled chimeric monoclonal antibody CG250.

OBJECTIVE: Carbonic anhydrase 9 recognized by chimeric monoclonal antibody cG250 is overexpressed on biliary cancers. The aim of this study was to determine the targeting of radiolabeled cG250 in patients with biliary cancer to explore a potential role of radioimmunotherapy. METHODS: Three (3) patients received a diagnostic dose 111In-cG250, and images were acquired 2 hours and 5 days after injection. Immediately after the last imaging session, 131I-cG250 was administered and images were acquired after 2 hours and 5 days. Visual and quantitative analyses was performed and tumor- to-background, tumor-to-normal liver-uptake ratios, and tumor uptake were calculated. RESULTS: Administration of 111In-cG250 in patients with biliary cancer did not reveal enhanced uptake in the cancer lesions on whole-body scans. The scans obtained after the 131I-cG250 administration showed slightly enhanced tumor uptake in 1 patient with cholangiocarcinoma stage II. In 2 patients with gallbladder carcinoma stage IV, neither 111In-cG250 nor 131I-cG250 showed targeting of known tumor lesions. Immunohistochemical analysis demonstrated CAIX expression in all 3 cases. There were no adverse events related to radiolabeled cG250 administration. CONCLUSIONS: 111In- or 131I-labeled cG250 is not suitable for biliary cancer targeting. Therefore, there is no basis to develop radioimmunotherapy based on radiolabeled cG250 in biliary cancer.

Final results of a phase I radioimmunotherapy trial using (186)Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma.

PURPOSE: Radioimmunotherapy (RIT) is an effective, new treatment modality for non-Hodgkin's lymphoma (NHL). The aim of this study was to determine the maximum tolerated dose and a first impression of the therapeutic potential of (186)Re-epratuzumab in patients with NHL. EXPERIMENTAL DESIGN: Patients with relapsed or refractory CD22-positive NHL of diverse histopathology and prior treatments received (99m)Tc-labeled epratuzumab (anti-CD22 IgG1), followed by RIT with (186)Re-epratuzumab 1 week later. Dose escalation of RIT was started at 0.5 GBq/m(2). Three patients were entered per dose level. If no dose-limiting toxicity occurred, the dose was increased by 0.5 GBq/m(2); otherwise three additional patients were included on that dose level. RESULTS: A total of 18 patients received a diagnostic dose of (99m)Tc-epratuzumab. Fifteen patients were actually treated with (186)Re-epratuzumab at four different dose levels, 0.5, 1.0, 1.5, and 2.0 GBq/m(2). During or after infusion of (186)Re-epratuzumab, no adverse reactions were seen. In all patients, a transient decrease of leukocyte and platelet levels was observed 1 month after treatment. At the 1.5-GBq/m(2) dose level, one grade 4 hematological toxicity was observed. At the highest dose level of 2 GBq/m(2), no grade 4 hematological toxicity was seen, but WBC and platelet counts of two of the three patients did not recover completely. One patient had a complete remission lasting 4 months. Four patients had a partial remission, lasting 3, 3, 6, and 14 months, respectively. Four patients had stable disease for 3, 3, 7, and 9 months, respectively. CONCLUSIONS: (186)Re-epratuzumab at a dose of 2.0 GBq/m(2) is well tolerated without major toxicity. A single dose of (186)Re-epratuzumab led to objective responses in 5 of 15 treated patients.

Phase I therapy study with (186)Re-labeled humanized monoclonal antibody BIWA 4 (bivatuzumab) in patients with head and neck squamous cell carcinoma.

PURPOSE: In previous studies, we have shown the potential of radioimmunotherapy (RIT) with (186)Re-labeled chimeric monoclonal antibody (MAb) U36 for treatment of head and neck cancer. A limitation of this anti-CD44v6 MAb, however, appeared to be its immunogenicity, resulting in human antichimeric antibodies in 40% of the patients. Aiming for a less immunogenic anti-CD44v6 MAb, the humanized MAb BIWA 4 (bivatuzumab) was introduced. In the present Phase I RIT study, we determined the safety, maximum tolerated dose (MTD), pharmacokinetics, immunogenicity, and therapeutic potential of (186)Re-labeled BIWA 4 in patients with squamous cell carcinoma of the head and neck. EXPERIMENTAL DESIGN: Twenty patients with inoperable recurrent and/or metastatic head and neck squamous cell carcinoma received a single dose of (186)Re-labeled BIWA 4 in radiation dose-escalation steps of 20, 30, 40, 50, and 60 mCi/m(2). Three patients received a second dose at least 3 months after the initial dose. After each administration, whole-body images as well as planar and tomographic images of the head and neck region were obtained, and the pharmacokinetics and the development of human antihuman antibody responses were determined. Radiation absorbed doses were calculated for whole body, red marrow, organs, and tumor. RESULTS: First and second administrations were all well tolerated, and targeting of tumor lesions proved to be excellent. The only significant manifestations of toxicity were dose-limiting myelotoxicity consisting of thrombo- and leukocytopenia and, to a lesser extent, oral mucositis (grade 2). Grade 4 myelotoxicity was seen in two patients treated with 60 mCi/m(2). The MTD was established at 50 mCi/m(2), at which level dose-limiting myelotoxicity was seen in one of six patients. Stable disease, varying between 6 and 21 weeks, was observed in three of six patients treated at the MTD level. The median tumor dose, recalculated to MTD level, was 12.4 Gy. The absorbed dose in red marrow was 1.82 +/- 0.11 cGy/mCi for males and 2.35 +/- 0.10 for females. Two patients experienced a human antihuman antibody response. Pharmacokinetics showed consistency across patients and within the three patients receiving (186)Re-BIWA 4 on two occasions. CONCLUSIONS: This study shows that (186)Re-labeled BIWA 4 can safely be administered, also in a repeated way. The MTD was established at 50 mCi/m(2). In comparison with the previously described anti-CD44v6 MAb U36, the humanized MAb BIWA 4 seems to be less immunogenic. The fact that antitumor effects were seen in incurable patients with bulky disease justifies the evaluation of RIT with (186)Re-labeled BIWA 4 in an adjuvant setting.

Dosimetric analysis of radioimmunotherapy with 186Re-labeled bivatuzumab in patients with head and neck cancer.

UNLABELLED: From December 1999 until July 2001, a phase I dose escalation study was performed with (186)Re-labeled bivatuzumab, a humanized monoclonal antibody against CD44v6, on patients with inoperable recurrent or metastatic head and neck cancer. The aim of the trial was to assess the safety and tolerability of intravenously administered (186)Re-bivatuzumab and to determine the maximum tolerated dose (MTD) of (186)Re-bivatuzumab. The data were also used for dosimetric analysis of the treated patients. Dosimetry is used to estimate the absorbed doses by nontarget organs, as well as by tumors. It can also help to explain toxicity that is observed and to predict organs at risk because of the therapy given. METHODS: Whole-body scintigraphy was used to draw regions around sites or organs of interest. Residence times in these organs and sites were calculated and entered into the MIRDOSE3 program, to obtain absorbed doses in all target organs except for red marrow. The red marrow dose was calculated using a blood-derived method. Twenty-one studies on 18 patients, 5 female and 16 male, were used for dosimetry. RESULTS: The mean red marrow doses were 0.49 +/- 0.03 mGy/MBq for men and 0.64 +/- 0.03 mGy/MBq for women. The normal organ with the highest absorbed dose appeared to be the kidney (mean dose, 1.61 +/- 0.75 mGy/MBq in men and 2.15 +/- 0.95 mGy/MBq in women; maximum kidney dose in all patients, 11 Gy), but the doses absorbed are not expected to lead to renal toxicity. Other organs with doses exceeding 0.5 mGy/MBq were the lungs, the spleen, the heart, the liver, the bones, and the testes. The doses delivered to the tumor, recalculated to the MTD level of 1.85 GBq/m(2), ranged from 3.8 to 76.4 Gy, with a median of 12.4 Gy. A good correlation was found between platelet and white blood cell counts and the administered amount of activity per kilogram of body weight (r = -0.79). CONCLUSION: Dosimetric analysis of the data revealed that the range of doses to normal organs seems to be well within acceptable and safe limits. Tumor doses ranged from 4 to 76 Gy. Given the acceptable tumor doses, (186)Re-labeled bivatuzumab could be a good candidate for future adjuvant radioimmunotherapy in patients with minimal residual disease.

Radioimmunodetection and radioimmunotherapy of head and neck cancer.

Radiolabeled monoclonal antibodies (MAbs) can add a dimension to diagnostic imaging and staging of metastatic head and neck cancer, as well as in eradication of this disease. The vast majority of malignancies arising in the oral cavity, pharynx and larynx are squamous cell carcinomas. This common cellular origin makes it attractive to search for appropriate tumor-associated antigens, which are preferentially expressed in these neoplasms. Radiolabeled MAbs directed against these antigens can be used for tumor detection and selective therapy, known as radioimmunoscintigraphy and radioimmunotherapy, respectively. The combination of MAbs with positron emission tomography (PET) is an attractive novel option to improve tumor detection and to facilitate MAb quantification in a therapeutic setting. Basic aspects of tumor targeting with MAbs, as well as a review of the clinical trials reported in the literature, including own results, are presented.

Biodistribution of 131I-, 186Re-, 177Lu-, and 88Y-labeled hLL2 (Epratuzumab) in nude mice with CD22-positive lymphoma.

UNLABELLED: Radioimmunotherapy (RIT) is a new and effective treatment modality in patients with non-Hodgkin's lymphoma. The monoclonal antibody (mAb) hLL2 (epratuzumab), a humanized mAb directed against the CD22 antigen, and which internalizes, can be labeled with various radionuclides. The biodistribution of hLL2 labeled with (131)I, (186)Re, (177)Lu, and (88)Y was studied in nude mice with subcutaneous human lymphoma xenografts in order to determine the most suitable of these four radionuclides for RIT with hLL2. METHODS: Human Ramos lymphoma xenografts were transplanted in cyclophosphamide-pretreated athymic BALB/c mice. Four groups of mice were injected intravenously with (131)I-, (186)Re-, (88)Y-, or (177)Lu-labeled hLL2, respectively. To determine the nonspecific tumor uptake, two groups of mice received (88)Y-labeled or (131)I-labeled control antibody, cG250. The biodistribution of the radiolabel was determined 1, 3, and 7 days postinjection (p.i.). RESULTS: Radiolabeled hLL2 had a higher tumor uptake than the nonspecific mAb at all time-points, irrespective of the radiolabel used. Tumor accretion of (88)Y- and (177)Lu-hLL2 was higher than tumor uptake of (131)I- and (186)Re-hLL2. Activity in the bone, represented by the femur without bone marrow, was higher for (177)Lu- and (88)Y-hLL2 than for (131)I- and (186)Re-hLL2 on day 7 p.i. CONCLUSION: The use of the residualizing radiolabels (88)Y and (177)Lu in combination with a mAb directed against an internalizing antigen resulted in higher uptake and better retention of the radiolabel in the tumor.

Enhancing tumor implantation and growth rate of Ramos B-cell lymphoma in nude mice.

The ability of a human B-cell lymphoma cell line to grow subcutaneously as tumors in nude mice was investigated. The effect of pretreating mice with cyclophosphamide or whole-body irradiation (WBI) was compared with no pretreatment of the mice. Both methods of pretreatment resulted in a higher tumor implantation rate, compared with that for non-pretreated controls. In mice that underwent WBI-pretreatment, a tumor implantation rate of 100% was observed, whereas mice pretreated with cyclophosphamide had a tumor implantation rate of 80%. In non-pretreated control mice, an implantation rate of only 50% was observed. Three weeks after injection, tumor size was significantly larger in mice of the pretreated groups, compared with that in mice of the group that did not receive pretreatment. Furthermore, particularly in the group pretreated with WBI, the tumors grew more synchronously, compared with tumors in the control group. Results of this study indicate that pretreatment with cyclophosphamide or WBI improves the tumor implantation rate of Ramos cells in nude mice, providing a workable animal model for studying human B-cell lymphoma.

Radioiodinated metaiodobenzylguanidine treatment of neuroendocrine tumors in adults.

Metaiodobenzylguanidine (MIBG), radioiodinated with (131)I, has been available for 25 years. Its role in the United States is limited to diagnostic imaging, whereas its therapeutic application in patients with neuroendocrine tumors for whom surgical treatment would not lead to a cure, has been approved in Europe. (131)I-MIBG treatments can be a valuable addition to the current gamut of treatment options for patients with metastatic neuroendocrine tumors, especially given the limited role for other systemic treatments, such as chemotherapy. There are basically two treatment strategies: one or two high-dose treatments or continuous low-dose treatments. (131)I-MIBG could induce symptomatic relief in the vast majority of patients treated, both following high-dose treatment and low-dose maintenance treatment. Biochemical responses can be observed in about half of the patients, whereas radiographic responses are described in roughly one third of the patients. Several articles suggested a survival benefit to patients treated with (131)I-MIBG. Side-effects of the treatment mainly consist of myelotoxicity, nausea, and hypothyroidism. Future developments are focused on the use of high-specific-activity (131)I-MIBG in high doses. The role of (131)I-MIBG in relation to other treatments remains to be established, although treatment (131)I-MIBG seems to be at least as effective as other systemic treatments, with limited side-effects.

A randomised controlled trial assessing the effect of oral diazepam on 18F-FDG uptake in the neck and upper chest region.

OBJECTIVE: A distinctive pattern of physiological symmetrical uptake of 18F-fluorodeoxyglucose (18F-FDG) in the neck and upper chest region is a phenomenon that is sometimes observed on positron emission tomography (PET) scans of some oncologic patients. Initially, it was assumed to be muscle uptake secondary to patient anxiety or tension, which could be prevented by diazepam treatment. However, PET-computed tomography data have shown that 18F-FDG uptake is not restricted to the musculature but is also localised within the non-muscular soft tissue, such as brown adipose tissue. The efficacy of benzodiazepine treatment to reduce this uptake has not been well established. Therefore, a randomised controlled trial was conducted to decide whether diazepam would decrease physiological 18F-FDG uptake in the neck and upper chest region (FDG-NUC). METHODS: A randomised, double-blind, placebo-controlled trial was conducted to assess the effect on FDG-NUC of 5 mg diazepam, given orally 1 h before 18F-FDG injection. Patients younger than 40 years, having or suspected to have a malignancy, were eligible for inclusion. The primary endpoint was FDG-NUC, as assessed by visual analysis of whole-body PET scans by two independent observers. The secondary endpoint was clinical relevance of FDG-NUC. RESULTS: Fifty-two patients were included between September 2003 and January 2005. Twenty-eight patients (54%) received placebo; 24 (46%) received diazepam. FDG-NUC was seen in 25% of the patients in the diazepam group versus 29% in the placebo group. This difference was not statistically significant. CONCLUSION: No beneficial effect of administration of diazepam could be established. Pre-medication with benzodiazepines to diminish physiological uptake of 18F-FDG in the neck and upper chest region is not indicated.

Antibody-guided radiation therapy of cancer.

Radioimmunotherapy (RIT) using radiolabeled monoclonal antibodies (MAbs) directed against tumor-associated antigens has evolved from an appealing concept to one of the standard treatment options for patients with non-Hodgkin's lymphoma (NHL). Inefficient localization of radiolabeled MAbs to nonhematological cancers due to various tumor-related factors, however, has refrained RIT from outgrowing the experimental stage in solid tumors. Still, small volume or minimal residual disease has been recognized as a potentially suitable target for radiolabeled antibodies. Several strategies are being explored aimed at improving the targeting of radiolabeled MAbs to solid tumors thus improving their therapeutic efficacy. In this review, a historical overview of the application of RIT is given and various aspects of the application of radiolabeled MAbs as anti-cancer agents are discussed. Finally, the clinical results of RIT of NHL, colorectal cancer, ovarian cancer, breast cancer, and renal cell cancer are reviewed.