[en] Purpose: Genetic profiling of biopsied tissue is the basis for personalized cancer therapy. However biopsied materials may not contain sufficient amounts of DNA needed for analysis. We propose a method to determine the adequacy of specimens for performing genetic profiling by quantifying metabolic activity. Methods: We measured the response of two radiation detectors to the activity contained in the minimum amount of tumor cells needed for genetic profiling in biopsy specimens obtained under 2-deoxy-2-("1"8F)fluoro-D-glucose ("1"8F-FDG) PET/CT guidance. The expected tumor cell concentration in biopsy specimens was evaluated from the amount of DNA needed (∼100 µg) and the number of pathology sections typically used for the analysis. The average "1"8F-FDG uptake per cell was measured by incubating KPC-4662 pancreatic tumor cells and HT-29 colorectal adenocarcinoma tumor cells in "1"8F-FDG containing solution (activity concentrations between 0.0122 and 1.51 MBq/mL and glucose concentrations of 3.1 and 1 g/L) for 1 to 1.75 hours and then measuring the activity of a known number of cells. Measurements of surrogate specimens obtained using 18G needle biopsies of gels containing these cells in expected concentrations (∼10"4 µL"−"1) were performed using an autoradiography CCD based device (up to 20 min exposure) and a scintillation well counter (∼1 min measurements) about 3 and 5 hours after the end of incubation respectively. Results: At start of autoradiography there were between 0.16 and 1.5 "1"8F-FDG molecules/cell and between 1.14 and 5.43×10"7 "1"8F-FDG molecules/mL. For the scintillation well counter, sample to minimum-detectable-count rate ratios were greater than 7 and the counting error was less than 25% for ≤80 s measurement times. Images of the samples were identifiable on the autoradiograph for ∼10 min and longer exposure times. Conclusion: Scintillation well counter measurements and CCD based autoradiography have adequate sensitivity to detect the tumor burden needed for genetic profiling in 18G core needle biopsies. Supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 and by a sponsored research agreement with Biospace Lab S.A.

[en] Full text: Intrahepatic artery Lipiodol labeled with generator-produced, β-emitting 188Re (17 hr; Eβ=0.53-0.70 MeV; Range=4 mm) localizes in and may effectively treat inoperable liver tumors. Although 188Re emits an imageable 155-keV γ ray (15%), its 478- and 633-keV β rays (2.3%) complicate imaging. Our objective was to optimize 188Re image quality and conjugate-view accuracy for quantitative imaging-based patient-specific dosimetry for 188Re-Lipiodol. Using an ADAC dual-EpicO-circumflex-detector gamma camera, 188Re intrinsic and extrinsic (with LEGP, MEGP, and HEGP collimation) uniformities using either 99mTc intrinsic or 188Re extrinsic flood corrections were evaluated. 188Re conjugate view count rate vs. activity concentration linearity as a function of scattering/attenuating medium thickness was then evaluated with and without corrections for attenuation (a 188Re transmission image) and for scatter and septal penetration, subtracting a fraction of counts in a lower-energy (109-140 keV)- and a higher-energy (170-201 keV)-window image, respectively, from the 20% (140-171 keV) photopeak image. Our phantom consisted of 5 10-ml vials containing 25 to 400 μCi/ml of 188Re with 0 to 6 cm at different positions (∼5 cm apart) between the detectors (60 cm apart) and with a 0- to 6-cm thickness of non-radioactive water between the vials and each detector. With a 99mTc intrinsic correction, 188Re intrinsic uniformity was excellent (<3%) but extrinsic uniformity prohibitively poor (>10% and 'tubey'), and was poorer the lower the energy rating of the collimation. Uniformity with HEGP collimation and an extrinsic 188Re correction was acceptable (<5%). Attenuation-corrected count rate-vs-188Re activity concentration linearity for any given thickness of water was excellent (r>0.95) and the slope (cps/pixel/μCi/ml) was constant +25% (vs +10% for 99mTc) for 0- to 6-cm thicknesses of water. Regardless of the fraction of counts subtracted, neither scatter nor septal-penetration correction improved the slope constancy. Conclusion: Downscatter/septal penetration of the 478- and 633-keV 188Re γ-rays complicates imaging of its 155-keV γ-ray. Using HEGP collimation and an extrinsic 188Re flood correction, however, high-quality gamma camera imaging of 188Re is achievable. Reasonably accurate (+25%) conjugate-view activity quantitation (using only the photopeak energy window) can be performed and used for maximum-permissible-activity patient-specific dosimetry for 188Re-Lipiodol therapy. (author)

[en] Full text: We have proposed and evaluated an iodine biokinetic model to reconstruct the organ doses of hyperthyroid patients. The biokinetic model has compartments that represent thyroid, iodide, protein-bound iodine, salivary glands, stomach, small intestine, urine and feces. The model was developed using archival measurement data from 3138 patients treated with ¹³¹I between 1946 and 1965 in thirty different hospitals for hyperthyroidism and other thyroid conditions. These subjects represent a subset of a much larger population studied for many years as part of the Thyrotoxicosis Therapy Follow-up Study (TTFUS, about 35,000 patients). Our measurement database has results of individual measurements of ¹³¹I activities in the thyroid, blood (inorganic and organic iodine), and urine for the 3138 patients at various times after administration of ¹³¹I, though not all patients have complete data. Information is also available on the administered activity, as well as estimates of the thyroid mass of each patient. The model rate constants have been derived to date, for several hundred patients using the ¹³¹I measurements and using the SAAMII computer code to build the biokinetic model. The proposed model takes into account the available patient data along with normative data from the literature. For patients with complete data, the organ doses are calculated based on the administered activity and the predictions of the amounts of iodide and protein-bound-iodine present in each organ and tissue as well as the biological behavior of ¹³¹I in the body. Presently, we are estimating the absorbed doses to major organs and tissues of the body for all 3138 patients who will make it possible to estimate organ doses to all hyperthyroid patients in the TTFUS according to type of disease, level of severity, age and gender. This paper will describe the proposed systemic model that fits the available data and will present the estimated organ and tissue doses. (author)

[en] The objective of this work was to develop and then validate a stereotactic fiduciary marker system for tumor xenografts in rodents which could be used to co-register magnetic resonance imaging (MRI), PET, tissue histology, autoradiography, and measurements from physiologic probes. A Teflon ^TM fiduciary template has been designed which allows the precise insertion of small hollow Teflon rods (0.71 mm diameter) into a tumor. These rods can be visualized by MRI and PET as well as by histology and autoradiography on tissue sections. The methodology has been applied and tested on a rigid phantom, on tissue phantom material, and finally on tumor bearing mice. Image registration has been performed between the MRI and PET images for the rigid Teflon phantom and among MRI, digitized microscopy images of tissue histology, and autoradiograms for both tissue phantom and tumor-bearing mice. A registration accuracy, expressed as the average Euclidean distance between the centers of three fiduciary markers among the registered image sets, of 0.2±0.06 mm was achieved between MRI and microPET image sets of a rigid Teflon phantom. The fiduciary template allows digitized tissue sections to be co-registered with three-dimensional MRI images with an average accuracy of 0.21 and 0.25 mm for the tissue phantoms and tumor xenografts, respectively. Between histology and autoradiograms, it was 0.19 and 0.21 mm for tissue phantoms and tumor xenografts, respectively. The fiduciary marker system provides a coordinate system with which to correlate information from multiple image types, on a voxel-by-voxel basis, with sub-millimeter accuracy--even among imaging modalities with widely disparate spatial resolution and in the absence of identifiable anatomic landmarks

[en] Full text: The aim of this study was to establish the safety and efficacy of the new radiopharmaceutical, Re-188 Lipiodol in the treatment of liver cancer. Eleven patients of liver cancer (HCC-8, Metastases from carcinoma of colon-2 and Carcinoid-1) were treated with Rhenium -188 Lipiodol. Nine patients were classified as ECOG- 1 and two were classified as ECOG- 3. Four patients received second dose of Rhenium-188 Lipiodol. Labeling of Rhenium-188 with Lipiodol was carried out according to a protocol developed under the CRP. Radioactivity (Dose range= 170-4181 MBq) was administered through the trans-arterial route by either selective (70%) or ultra-selective (30%) hepatic arteriography. Dosimetric evaluations were carried out using a spreadsheet developed under the CRP. All patients were followed up for periods ranging from 1-23 months (average = 9 months) after treatment, by clinical examination, liver function tests, hematological examinations and CT scans of liver. Rhenium-188 Lipiodol treatment was well tolerated by all patients. No immediate systemic complications were noted within 72 hrs. of therapy. Three patients developed mild fever in the immediate post-therapy period, which subsequently subsided and 1 patient developed interstitial non-specific pneumonitis at 8 weeks of second therapy, which resolved completely after 10 days of treatment with corticoids. Follow-up CT scans revealed significant reduction in tumor size in seven patients (30-75%). Tumor size remained unaltered in one, while in one disease progression was noted. Best results were seen in patients with HCC who demonstrated excellent tumor concentration of radioactivity. Four patients died, 3 patients of HCC who immuno-histochemical analysis the presence of tumors was had extensive disease (tumor size more than 1000 gms.) died within a period of one month after therapy. One patient with a lesion of 7 cm and Child B suffered progressive liver failure two months after treatment. One patient of carcinoid tumor, in whom there was 20% regression in tumor size, survived for a period of seven months following treatment. All six surviving patients showed significant response (both anatomic as well as functional) to treatment. Patients with HCC with longer follow up who received 1 dose required second dose at 9 months and patients who received 2 doses between 8 and 12 weeks showed stable size until 14 months. From our study, it can be concluded that Rhenium-188 Lipiodol is a promising and safe radiopharmaceutical for the treatment of liver cancer. Further studies to establish the efficacy of treatment are being carried out through a prospective Phase-II multi-center trial on a large number of patients. (author)

[en] This paper describes the results of a Phase I study conducted by the International Atomic Energy Agency (Vienna) to determine the safety of trans-arterial Re-188 Lipiodol (radio-conjugate) in the treatment of patients with inoperable hepatocellular carcinoma (HCC). Rhenium-188 Lipiodol conjugate was prepared using a HDD (4-hexadecyl 1-2, 9, 9-tetramethyl-4, 7-diaza-1, 10-decanethiol) kit developed in Korea, and lipiodol. Sixteen patients received one treatment of radio-conjugate. The level of radio-conjugate administered was based on radiation absorbed dose to critical normal organs, calculated following a 'scout' dose. The organs at greatest risk for radiation toxicity were the normal liver, the lung and the bone marrow. A specially designed EXCEL Spreadsheet was used to determine maximum tolerated dose (MTD), defined as the amount of radioactivity calculated to deliver no more than 12 Gy to lungs or 30 Gy to liver or 1.5 Gy to bone marrow. These doses have been found to be safe in multiple trials using external beam therapy and systemically administered radiopharmaceuticals. Patients were followed for at least twelve weeks after therapy, until recovery from all toxicity. Some patients were re-treated if there was no evidence of disease progression. The clinical parameters which were evaluated included toxicity; response as determined by contrast-enhanced CT; palliation of symptoms, and overall survival at six months; and quality of life parameters, including performance status (Karnofsky) and hepatic function (Child's classification). All sixteen patients had both the 'scout' dose and the treatment dose. In the majority of patients, from the 'scout' dose studies, the radiation absorbed dose to normal liver was the limiting factor to the treatment dose, where the maximum tolerated dose (MTD) was determined by the radiation dose to liver, or by dose to lung. Radiation dose to bone-marrow was negligible and was thus not factor for the MTD calculations. Side-effects were minimal and usually presented as right hypochondrial discomfort and low-grade fever. Liver function tests at 24 and 72 hours showed no significant changes and complete blood counts at one week, four weeks and 12 weeks showed no changes (no bone-marrow suppression). The results of this Phase I study show that Rhenium-188 Lipiodol is a safe and cost-effective radiopharmaceutical for treatmenting of primary HCC via the transarterial route, and the new therapeutic procedure should be subjected to further evaluation to determine its efficacy. (author)