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Peptide receptor radionuclide therapy (PRRT) is an effective treatment for metastatic neuroendocrine tumors. Delivering a sufficient tumor radiation dose remains challenging because of critical-organ dose limitations. Adding

Localization of the site of the unknown primary tumor is critical for surgical treatment of patients presenting with neuroendocrine tumor (NET) with metastases. Methods: Forty patients with metastatic NET and unknown primary site underwent 68Ga-DOTATOC PET/CT in a single-site prospective study. The 68Ga-DOTATOC PET/CT was considered true-positive if the positive primary site was confirmed by histology or follow-up imaging. The scan was considered false-positive if no primary lesion was found corresponding to the 68Ga-DOTATOC–positive site. All negative scans for primary tumor were considered false-negative. A scan was classified unconfirmed if 68Ga-DOTATOC PET/CT suggested a primary, however, no histology was obtained and imaging follow-up was not confirmatory. Results: The true-positive, false-positive, false-negative, and unconfirmed rates for unknown primary tumor were 38%, 7%, 50%, and 5%, respectively. Conclusion: 68Ga-DOTATOC PET/CT is an effective modality in the localization of unknown primary in patients with metastatic NET.

The worldwide incidence of head and neck cancer is estimated at approximately 643,000 ([1][1]). In the United States, approximately 53,640 new head and neck cancers will be diagnosed in 2013, with 11,520 deaths expected ([2][2]). The treatment choice for head and neck cancer depends on the primary

The purpose of this study was to conduct a phase I trial of 90Y-DOTATOC to determine the dose-toxicity profile in children and young adults with somatostatin receptor–positive tumors. Methods: A 3 × 3 design was used to determine the highest tolerable dose of 90Y-DOTATOC, with administered activities of 1.11, 1.48, and 1.85 GBq/m2/cycle given in 3 cycles at 6-wk intervals. An amino acid infusion was coadministered with the radiopharmaceutical for renal protection. Eligibility criteria included an age of 2–25 y, progressive disease, a positive lesion on 111In-diethylenetriaminepentaacetic acid-D-Phe1-octreotide scanning, a glomerular filtration rate of 80 mL/min/1.73 m2 or more, bone marrow cellularity of 40% or more or stored autologous hematopoietic stem cells, 60% or more on the Lansky Play Scale, and informed consent. Results: Seventeen subjects (age, 2–24 y) received at least 1 dose of 90Y-DOTATOC; diagnoses included neuroblastoma, embryonal and astrocytic brain tumors, paraganglioma, multiple endocrine neoplasia IIB, and neuroendocrine tumors. No dose-limiting toxicities and no individual dose reductions due to renal or hematologic toxicity were noted. No complete responses were observed; 2 subjects experienced partial response, 5 had minor responses, 6 experienced stable disease, 2 had progressive disease, and 2 withdrew. Conclusion: Peptide receptor radionuclide therapy with 90Y-DOTATOC is safe in children and young adults and demonstrated a 12% partial response plus 29% minor response rate in patients with somatostatin receptor–positive tumors. No dose-limiting toxicities were observed. The recommended phase II dosing is 3 cycles of 1.85 GBq/m2/dose of 90Y-DOTATOC coadministered with amino acids.

TO THE EDITOR: Therapeutic doses of cold fluorothymidine (FLT) used as antiviral therapy have been shown to cause renal, hepatic, and hematologic toxicity within 4 wk of treatment ( [1][1] ). This observed toxicity was of concern when investigational studies using 18F-FLT were initiated in the

The purpose of this study was to investigate the kinetic behavior of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) before and early after initiation of chemoradiation therapy in patients with squamous cell head and neck cancer.A total of 8 patients with head and neck cancer underwent (18)F-FLT PET scans (7 patients at baseline and after 5 d [10 Gy] of radiation therapy given with concomitant chemotherapy and 1 patient only at baseline). Dynamic PET images were obtained with concurrent arterial or venous blood sampling. Kinetic parameters including the flux constant of (18)F-FLT based on compartmental analysis (K-FLT), the Patlak influx constant (K-Patlak), and standardized uptake value (SUV) were calculated for the primary tumor and (18)F-FLT-avid cervical lymph nodes for all scans.Mean pretreatment values of uptake for the primary tumor and cervical nodes were 0.075 +/- 0.006 min(-1), 0.042 +/- 0.004 min(-1), and 3.4 +/- 0.5 (mean +/- SD) for K-FLT, K-Patlak, and SUV, respectively. After 10 Gy of radiation therapy, these values were 0.040 +/- 0.01 min(-1), 0.018 +/- 0.016 min(-1), and 1.8 +/- 1.1 for K-FLT, K-Patlak, and SUV, respectively. For all lesions seen on pretherapy and midtherapy scans, the correlation was 0.90 between K-FLT and K-Patlak, 0.91 between K-FLT and SUV, and 0.99 between K-Patlak and SUV.The initial (18)F-FLT uptake and change early after treatment in squamous head and neck tumors can be adequately characterized with SUV obtained at 45-60 min, which demonstrates excellent correlation with influx parameters obtained from compartmental and Patlak analyses.

(131)I-Metaiodobenzylguanidine (MIBG) and (90)Y-DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) have been used as radiotherapeutic agents for treating neuroendocrine tumors. The tumor dose delivered by these agents is often insufficient to control or cure the disease. However, these 2 agents used together could potentially increase tumor dose without exceeding the critical organ dose because the dose-limiting tissues are different. In this paper, we investigate the conditions in which combined-agent therapy is advantageous and we quantify the expected tumor-dose gain.A series of equations was derived that predicted the optimal combination of agents and the fractional increase in tumor dose available from combined-agent therapy with respect to either (131)I-MIBG or (90)Y-DOTATOC. The results obtained from these derivations were compared with direct dose calculations using published dosimetric organ values for (131)I-MIBG and (90)Y-DOTATOC along with critical organ-dose limits. Tumor dose was calculated as a function of the tumor-dose ratio, defined as the (90)Y-DOTATOC tumor dose per megabecquerel divided by the (131)I-MIBG tumor dose per megabecquerel. Comparisons were made between the dose delivered to tumor with single-agent therapy and the dose delivered to tumor with combined-agent therapy as a function of the tumor-dose ratio and the fraction of activity contributed by each agent.The dose model accurately predicted the optimal combination of agents, the range at which combined-agent therapy was advantageous, and the magnitude of the increase. For the published organ dosimetry and critical organ-dose limits, combined-agent therapy increased tumor dose when the tumor-dose ratio was greater than 0.67 and less than 5.93. The maximum combined-agent tumor-dose increase of 68% occurred for a tumor-dose ratio of 2.57, using 92% of the maximum tolerated (90)Y-DOTATOC activity supplemented with 76% of the maximum tolerated activity of (131)I-MIBG. Variations in organ dose per megabecquerel and dose-limiting values altered both the magnitude of the increase and the range at which combined-agent therapy was advantageous.Combining (131)I-MIBG and (90)Y-DOTATOC for radiotherapy of neuroendocrine tumors can significantly increase the delivered tumor dose over the dose obtained from using either agent alone. Prior knowledge of the normal-organ and tumor dosimetry of both agents is required to determine the magnitude of the increase.

Nuclear imaging techniques such as bone scans, metaiodobenzylguanidine (MIBG) scans, and (111)In-diethylenetriaminepentaacetic acid-octreotide scans have greatly increased the sensitivity and specificity of both diagnostic and follow-up protocols for pediatric solid tumors. Molecular targets that are specific for certain pediatric tumors are now being developed. Targets include cell membrane receptors targeted by specific ligands, subcellular organelles targeted by false transmitters, and cellular proteins targeted by antibodies. This review focuses on the use of MIBG (which is a false transmitter) and octreotide (which is a ligand for G protein receptor) in the diagnosis and treatment of solid tumors that affect children and young adults.

Because of the presence of cell membrane somatostatin receptors (SSTRs), many neuroendocrine tumors will bind analogs of somatostatin. (90)Y-Dodecanetetraacetic acid-Phe1-Tyr3-octreotide (SMT 487) is an SSTR radiopharmaceutical currently under investigation as a therapeutic option for neuroendocrine tumors. Although there are a variety of methods for evaluating response to a given cancer therapy, an important indicator of success is the impact on the clinical status of the patient. The purpose of this work was to develop a semiquantitative method and assess the clinical effectiveness of (90)Y-SMT 487 therapy in patients with neuroendocrine tumors.A scoring system was developed to evaluate clinical response that included the following parameters: weight, health status score (determined by the patient), Karnofsky score, and tumor-related symptoms.We applied this scoring system to 21 patients who had completed 3 cycles of therapy with (90)Y-SMT 487. Fourteen of the 21 showed a favorable clinical response, whereas 5 were clinically stable after treatment and 2 showed evidence of clinical progression. There was also a significant reduction in the amount of octreotide being used after completion of (90)Y-SMT 487 therapy in the 20 patients who were on this medication.Using this scoring method, (90)Y-SMT 487 appears effective in improving the clinical status of patients with (111)In-pentetreotide-positive neuroendocrine tumors.