Radioimmunoimaging of Non-Small Cell Lung Cancer with 111In- and 99MTc-Labeled Monoclonal Anti-Cea-Antibodies

Radiolabeled monoclonal anti-CEA antibodies were used for radioimmunolocalization (RIL) of non-small cell lung cancer; in 30 patients with ¹¹¹In labeled anti CEA F(ab')₂ fragment (BW 431/31) and in 16 with ^99mTc-labeled intact MoAb (BW 431/26). RIL results were compared with those of other imaging modalities. Paraffin sections from some patients were also studied immunohistochemically using anti-CEA antibody. Patients with ¹¹¹In labeled MoAB were imaged twice 1-4 days after injection and for image enhancement pulmonary and liver/spleen subtraction were performed. Twenty-seven of 28 primary tumors were positive and metastases were detected in all patients The total number of lesions was 78 of which 61 (78%) could be detected by RIL. For verification CT was applied to the study of 46 lesions detected by RIL. We found 6 unknown lesions subsequently verified histologically. Unsing subtraction techniques we detected 9 lesions in 4 patients, later verified as plumonary metastases, not detected in unprocessed images. Pleural, mediastinal and pericardial lesions were also better delineated in subtracted images than in unprocessed images. Imaging of non-small cell lung cancer with ^99mTc-labeled MoAB was performed twice 4-24 h after injection. RIL results were compared with other imaging methods; CT US, conventional radiography, and immunohistochemistry. Twelve out of 16 patients with suspected or known lung cancer had positive immunoscintigrams; 19 of 25 lesions could be detected by RIL. There were 5 false positive and 2 true negative findings. Immunoperoxidase (IP) stainings of paraffin sections of the tumours from 7 patients were performed using two different anti-CEA antibodies; BW 431/26 and ZCEA_l. None of the seven tumors examined by immunohistochemistry were negative when stained by BW 431/26, which was the antibody used for immunoscintigraphy.     

A new 111In-bleomycin complex for combined radiotherapy and chemotherapy

Six days after tumor transplantation three daily intraperitoneal doses of 0.9% NaCl, bleomycin (BLM), or a new 111In-bleomycin complex (BLMC, 15 microCi/g body weight) were administered to glioma-bearing mice. After therapy, tumors in mice treated with 111In-BLMC were smaller than those treated with BLM. Sixteen days after the first injection tumor size for 111In-BLMC-treated mice was 560 (240-1,030) mm3, 1,980 (1,400-3,290) mm3 for BLM (P less than 0.025), and 4,830 (2,580-9,180) mm3 for NaCl (0.1 less than P less than 0.2). Thirteen days after tumor transplantation glioma-bearing mice received single intratumor injection of 0.9% NaCl, BLM, or 111In-BLMC (1.5 mCi, carried by 0.5 mg BLM/g tumor weight). The average tumor size for 111In-BLMC was smaller than that for BLM by a factor of 2.5-3.7. Host weights for these two groups were similar, and morphologic abnormalities were not found in kidney or liver.     

Dual-isotope lymphoscintigraphy using albumin nanocolloid differentially labeled with 111In and 99mTc

The aim of this study was to develop and evaluate ¹¹¹In- and ^99mTc-labeled derivatives of albumin nanocolloid (NC) for dual-label lymphoscintigraphy to allow simultaneous comparison of lymphatic flow from different tissue planes draining a tumour bed for accurate identification of sentinel lymph nodes (SLN). Using the chelator, p-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (DOTA), ¹¹¹In-DOTA-NC and ^99mTc-DOTA-NC were compared in vitro with respect to stability of labeling, colloidal status and particle size, then in vivo by measuring their clearance rates from a subcutaneous injection depot. ¹¹¹In-DOTA-NC and ^99mTc-DOTA-NC were indistinguishable on the basis of in vitro criteria. Their in vivo clearance rates, however, were disparate (0.0015 to 0.075 min^-1 for ¹¹¹In and 0.0072 to 0.067 min^-1 for ^99mTc), ¹¹¹In being faster in three studies and markedly slower in three. This demonstrates that even when dual-labeled radiotracers behave identically in vitro, they will not necessarily do so in vivo. Further work is needed to develop dual-labeled NC.     

Distribution of DNA strand breaks produced by iodine-123 and indium-111 in synthetic oligodeoxynucleotides

Antigene radiotherapy, a procedure based on delivery of short-range Auger-electron-emitting radioisotopes to target genes via sequence-specific triplex-forming oligonucleotides, has been successfully demonstrated in vitro using the well-studied radionuclide ¹²⁵I. To proceed with in vivo trials, Auger electron emitters with shorter half-lives than ¹²⁵I are required. Here we report a study of the efficiency and distribution of sequence-specific DNA strand breaks produced by decay of ¹²³I and ¹¹¹In. ¹²³I and ¹¹¹In were introduced into triplexand duplex-forming oligodeoxyribonucleotides (ODNs) through carbohydrate linkers of various lengths. Labeling with radioiodine was performed through tributylstannylbenzamide intermediates while ¹¹¹In was attached via DTPA. The Auger-emitter-labeled ODNs were hybridized to a single-stranded DNA target, to form duplexes. After decay accumulation, the target DNA samples were assayed for strand breaks using a sequencing gel-electrophoresis technique. For the first time, we observed footprints of DNA strand breaks produced by ¹²³I and ¹¹¹In. Most of the breaks were located within 10 nucleotides from the decay site. The yield of strand breaks per decay varies; decay of ¹¹¹In breaks DNA almost 10 times more effectively than decay of ¹²³I. Both ¹²³I and ¹¹¹In are less effective in breaking DNA strands than ¹²⁵I, which reflects the higher total energy of the Auger decay process of ¹²⁵I.     

Ellagic acid binding to DNA as a possible mechanism for its antimutagenic and anticarcinogenic action

Ellagic acid (EA), a plant phenol, is reported to possess antimutagenic and anticarcinogenic activity. In the present study, explants of esophagus, trachea, colon, forestomach and bladder from young male Sprague-Dawley rats were incubated in medium containing [³H]EA (4.5 μCi/ml) for 24 h at 37° C. DNA from these explants was extracted, purified and quantitated to determine [³H]EA binding to the DNA. Significant covalent binding of [³H]EA to DNA occurred in all the explants. Calf thymus DNA incubated in 0.05 M sodium phosphate buffer containing [³H]EA covalently bound [³H]EA in a concentration dependent manner. Furthermore covalent binding of [³H]EA to calf thymus DNA was inhibited by the addition of unlabeled EA that was concentration dependent over a range of 50–150 μM and by the addition of unlabeled adenosine, cytidine, guanosine or thymidine at a concentration of 1.0 mM. These results suggest that one of the mechanisms by which EA inhibits mutagenesis and carcinogenesis is by forming adducts with DNA, thus masking binding sites to be occupied by the mutagen or carcinogen.     

Cytotoxic effect of radiolabeled C5a on U937 cells in vitro

We studied whether the receptor (R) for C5a could be exploited to deliver the radiolabeled ligand into U937 cells. A doseresponse for uptake of ¹²⁵I-C5a was demonstrated. Incorporation of [³H]leucine by unstimulated or γ-INF-stimulated U937 cells treated with ¹²⁵I-C5a, was significantly lower compared with cells treated with ¹²⁵I alone. Trypan blue exclusion experiments indicated that γ-INF stimulated cells incubated with ¹²⁵I-C5a were less viable than cells exposed to ¹²⁵I or C5a alone. The results suggest that ¹²⁵I-C5a is internalized into myeloid cells via C5a-R and is more cytotoxic in vitro than the radiolabel alone, but only at/above a specific activity of 4 μCi/μg.     

Effects of a prospective antitumor agent, 1,4-bis(2''-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane diperchlorate, on cultured mammalian cells

The effects of 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane diperchlorate (CBH; NSC 57198) on cell viability, growth, progression through the cell cycle, survival, and differentiation were investigated in suspension cultures of murine lymphocytic leukemia (L1210) and erythroleukemic (FL) cells and normal human lymphocytes stimulated with phytohemagglutinin (PHA) and in adherent cultures of Chinese hamster ovary (CHO) cells. CBH was equally cytotoxic toward stationary and exponentially growing CHO cells. Cell viability was diminished by 50% following 24 hr exposure to approximately 50 μg CBH per ml. Treatment of quiescent human lymphocytes for 24 hr with up to 100 μg CBH per ml did not appreciably diminish cell viability though the subsequent stimulation of such lymphocytes with PHA was inhibited in a dose dependent fashion. L1210, FL cells, and PHA stimulated human lymphocytes were equally sensitive to CBH, 50% inhibition of growth was obtained following 24 hr treatment with 25 μg CBH per ml. Incubation for up to 48 hr with CBH did not result in differentiation of FL cells to mature hemoglobin containing cells. Constant exposure of L1210 cells and PHA-stimulated human lymphocytes to 10-50 μg CBH per ml resulted in accumulation of cells in G₂ + M phase; higher drug concentrations resulted in cell arrest in mid to late S phase and G₂ phase. A short 1-hr pulse of the drug resulted in a transient accumulation of L1210 cells in S and G₂ phases. However, cells recovered from a short pulse of drug and by 48 hr, both cell proliferation and the cell cycle distribution appeared normal. A detailed analysis of cell cycle progression of L1210 cells in the presence of the drug indicated that the duration of G₂ phase was extended at low concentrations (10 μg/ml) while the transit of cells through S was retarded with subsequent accumulation in late S and G₂ phase at higher (50 μg/ml) concentrations. Concomitant with cell arrest in S and G₂ phase an increase in cellular RNA content indicating unbalanced growth was observed. This state of unbalanced growth was reversible in cultures exposed to a 1-hr pulse of up to 100 μg CBH per ml; cellular RNA content returned to control values by 48 hr. No effect on nuclear chromatin as assayed by acid denaturation was observed. Though the exact mechanism of drug action is not known, the data are not incompatible with the drug acting as an alkylating agent.     

Somatostatin Receptor Scintigraphy of Carcinoid Tumours Using the [111In-Dtpa-D-Phe1]-Octreotide

Somatostatin-receptor scintigraphy using the ¹¹¹In-labelled somatostatin-analogue octreotide ([¹¹¹In-DTPA-D-Phe¹]-octreotide) was performed in 40 patients with carcinoid tumours. In 31/40 patients, this scintigraphy proved positive compared with the 33/40 patients whose tumours were disclosed on CT scans. In addition, 18 previously unidentified lesions were detected with this scintigraphy. Two of these lesions represented previously undetectable primary tumours. It is concluded that somatostatin receptor scintigraphy using [¹¹¹In-DTPA-D-Phe¹]-octreotide has a future role in the staging of patients with carcinoid disease.     

Radiation spectra of 111In, 113mIn and 114mIn

The radiation spectra of ¹¹¹In, ^113mIn, and ^114mIn are calculated with the Monte Carlo computer program IMRDEC. The relaxation probabilities are taken from the EADL file of the Lawrence Livermore National Laboratory. Because this file does not include data for some N and O transitions, these were additionally determined by applying the Kassis rule. Two schemes are applied to calculate the transition energies: 1) a simple (Z + 1)/Z scheme, and 2) accurate calculation solving the relativistic Dirac equations. It is shown that using the extended set of relaxation probabilities leads to generation of many additional low-energy Auger and CK electrons if the (Z + 1)/Z rule is applied. On the other hand, the emissions of almost all these electrons are rejected if their energies are calculated solving the Dirac equations taking into consideration realistic electron vacancies.     

Heterogeneity of peripheral blood T-cell colony-forming cells in patients with T-cell malignancies

Some peripheral blood clonogenic T-cells from patients with T-cell malignancies can generate colonies in methylcellulose in the absence of added growth factors or mitogen stimulation (T-CFC_S). T-CFC from these patients were also able to form colonies in semi-solid media in the presence of added growth factors (T-CFC_i. T-CFC_S, in contrast to T-CFC_i, were highly clonogenic cells possessing self-renewal capacity in the absence of added growth factors. T-CFC₅ were in cell cycle and more sensitive to Ara-C or ADM (D₁₀ = 0.009 and 0.025 μg/ml respectively) than T-CFCi (D₁₀ = 1 and 2 μg/ml respectively). Furthermore, T-CFC₅ were more radiosensitive (D_o < 1.1 Gy) than T-CFC. (D_o <5 Gy). T-cell precursors from patients with immature blast cells (E⁻, OKT3⁻, OKT6⁺, OKT10⁺) were independent of added growth factors for their in vitro proliferation whereas in cases with mature blast cells (E⁺, OKT3⁺) T-CFC were significantly more dependent. These observations strongly suggest that T-CFC₅ and T-CFC_i represent different cell subsets.

The phenotype of pooled induced and spontaneous T-cell colonies was highly individualized. However, colonies contained a significant proportion of relatively immature T-cells as assessed by the proportion of OKT6⁺, OKT10⁺, OKT3⁺ and E⁺ cells. The phenotype of colony cells was quite similar to that observed on fresh leukemic cells suggesting a defect of the in vitro differentiation of both T-CFC₅ and T-CFC_i.     

Antiproliferative Activity of Mammalian Lignan Derivatives Against the Human Breast Carcinoma Cell Line, ZR-75-1

The effect of each of twelve mammalian lignun derivatives on the growth of human mammary tumor ZR-75-1 cells was examined. At a concentration less than 10 μ g/ml, tumor cell growth was inhibited from 18-68%. The effect of 2,3-dibenzylbutane-1,4-diol (hattalin) was found to be strongest, inhibiting growth by 50% at a concentration (EC₅₀ of 2.1 μ g/ml. Hattalin inhibited membrane Na^%, K^%-ATPase of canine kidney cortex. It also inhibited the ATPase of the plasma membrane fraction from both cultured cells and a section of human breast cancer tissue at a concentration ranging from 0.5 to 2.0 mM. However, only a few percent of membrane ATPase from either ZR-75-1 cells or breast carcinoma tissue was inhibited by 2.0 mM of ouabain, suggesting that the target ATPase of hattalin was other than ouabainsensitive ATPase. The relative incorporation of [³H]thymidine per 1 10⁵ cells into the acid-precipitable fraction of ZR-75-1 cells was not affected by 1-50 μg/ml of hattalin, while a marked decrease resulted from 1-10 μg/ml of 5-fluorouracil (5-FU). These results suggest that the suppressive effect of hattalin on tumor cell growth my not occur through inhibition of DNA synthesis but rather partly by inhibition of the plasma membrane ATPase other than Na^% and K^% -dependent ones.     

Heterogeneous Effects of G-CSF and GM-CSF on Cell Growth and Ara-C Cytotoxicity in Childhood Leukemias Which Express Myeloid Markers

It is uncertain if acute lymphoblastic leukemia (ALL) cells expressing myeloid makers can respond to granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF). We investigated the effects of G-CSF (0.01 μg/ml) and GM-CSF (0.01 μg/ml) on [³H]thymidine (TdR) uptake, and the cytotoxicity of l-β-D-arabinofuranosylcytosine (ara-C) in leukemia cells from 17 pediatric patients. ALL cells without myeloid markers did not respond to G-CSF or GM-CSF. On the other hand, these cytokines enhanced the [³H]TdR uptake and cell growth, not only of AML cells but also of ALL cells expressing myeloid antigens. However, G-CSF and GM-CSF did not always enhance the growth inhibitory effect of the cell cycle specific drug ara-C when the cells were co-cultured with the drug. There was no relationship between cell growth and the amount of [³H]TdR incorporation or the intracellular ara-CTP level. These results indicate the heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C sensitivity in childhood leukemia cells.     

Treatment with High Dose [111In-DTPA-D-PHE1]-Octreotide in Patients with Neuroendocrine Tumors: Evaluation of Therapeutic and Toxic Effects

Carcinoid tumors and endocrine pancreatic tumors often express somatostatin receptors (sst). Tumor spread may be visualized by sst scintigraphy using [¹¹¹In-DTPA-D-Phe¹]-octreotide. In this study, tumor targeting therapy with [¹¹¹In-DTPA-D-Phe¹]-octreotide at high doses (6 GBq every third week) was used to treat patients with sst-expressing tumors. Five patients entered the protocol and three were evaluable for response, while all could be evaluated for toxicity. Two patient responded with a significant reduction in tumor markers (>50%). The third patient showed increasing levels of tumor markers. Side effects were expressed as depression of bone-marrow function. In one patient a grade 4 reduction in platelet count was observed requiring several thrombocyte transfusions. In another two patients platelet counts decreased significantly. We conclude that treatment with [¹¹¹In-DTPA-D-Phe¹]-octreotide can be used in patients with neuroendocrine tumors but blood parameters have to be carefully monitored to avoid severe side effects.     

Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours

Peptide Receptor Radionuclide Therapy (PRRT) with radiolabelled somatostatin analogues is a promising treatment option for patients with inoperable or metastasised neuroendocrine tumours. Symptomatic improvement may occur with all of the various ¹¹¹In, ⁹⁰Y, or ¹⁷⁷Lu-labelled somatostatin analogues that have been used. Since tumour size reduction was seldom achieved with ¹¹¹Indium labelled somatostatin analogues, radiolabelled somatostatin analogues with beta-emitting isotopes like ⁹⁰Y and ¹⁷⁷Lu were developed. Reported anti-tumour effects of [⁹⁰Y-DOTA⁰,Tyr³]octreotide vary considerably between various studies: Tumour regression of 50% or more was achieved in 9 to 33% (mean 22%). With [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate treatments, tumour regression of 50% or more was achieved in 28% of patients and tumour regression of 25 to 50% in 19% of patients, stable disease was demonstrated in 35% and progressive disease in 18%. Predictive factors for tumour remission were high tumour uptake on somatostatin receptor scintigraphy and limited amount of liver metastases. The side-effects of PRRT are few and mostly mild, certainly when using renal protective agents: Serious side-effects like myelodysplastic syndrome or renal failure are rare. The median duration of the therapy response for [⁹⁰Y-DOTA⁰,Tyr³]octreotide and [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate is 30 months and more than 36 months respectively. Lastly, quality of life improves significantly after treatment with [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate. These data compare favourably with the limited number of alternative treatment approaches, like chemotherapy. If more widespread use of PRRT is possible, such therapy might become the therapy of first choice in patients with metastasised or inoperable gastroenteropancreatic neuroendocrine tumours. Also the role in somatostatin receptor expressing non-GEP tumours, like metastasised paraganglioma/pheochromocytoma and non-radioiodine-avid differentiated thyroid carcinoma might become more important.     

Increased binding of benzo[a]pyrene metabolites to lymphocytes from patients with lung cancer

This study was performed to determine whether lymphocytes from individuals with lung cancer were more likely to bind benzo[a]pyrene (BP) metabolites in an in vitro test. The in vitro system consisted of peripheral blood lymphocytes incubated with increasing concentrations of [³H]benzo[a]pyrene in the presence of β-naphthoflavone-induced rat liver microsomes and a NADPH-generating system. The radioactivity bound to a TCA-precipitate of the lymphocytes was determined. The apparent affinity (K_m) and maximal binding (V_max) of this binding were calculated from double reciprocal plots of the data. Seven patients with primary lung cancer (squamous cell carcinoma and undifferentiated small cell carcinoma), none of whom had smoked for at least 2 months, were studied as were 10 lung cancer free smokers, and the results compared with 13 age- and sex-matched controls. In lymphocytes from patients with primary lung cancer, V_max of radiolabel bound to TCA-precipitable material was almost double that of non-smoking controls (205 ± 19.2 pmol · 2h · 10⁶ cells vs. 121 ± 10.8 pmol · 2h · 10⁶ cells, mean ± S.E.M., P < 0.01). Among individuals without lung cancer, smokers did not differ from non-smokers. In addition, there was no difference in K_m of radiolabel binding to lymphocytes from patients in all 3 groups. It is concluded that binding of carcinogenic metabolites to cell components is increased in patients with lung cancer. Further studies are required to determine whether this increased binding is related to individual susceptibility of some smokers to lung cancer.     

Enhanced killing of human small cell lung cancer by hyperthermia and indium-111-bleomycin complex.

Indium-111-bleomycin complex (111In-BLMC) is a radiopharmaceutical agent that produces tumor regression in mouse glioma in vivo and kills human small cell lung cancer (SCLC) cells in vitro. The interaction between hyperthermia and 111In-BLMC against human SCLC (N417) cells was studied for bleomycin (BLM) (15 micrograms/ml) or 111In-BLMC (40-50 microCi carried by 15 micrograms BLM/ml) for 5 min or 1.5, 2, or 4 hr at 37 degrees C or 43 degrees C exposures. Cell survival was determined by colony formation in soft agarose. There was a synergistic effect for 111In-BLMC and hyperthermia for cell killing. At 37 degrees C, the percent survival of N417 cells for BLM alone was 25.9%, and for 111In-BLMC it was 13.2%; at 43 degrees C, survival was 5.3% for BLM alone and 1.2% for 111In-BLMC by a 4 hr treatment. Effectiveness was greater when 111In-BLMC was combined with hyperthermia.     

Comparative biodistribution of potential anti-glioblastoma conjugates [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF in normal mice

EGF-receptors (EGFR) are overexpressed in gliomas, as well as in tumors of breast, lung, and urinary bladder. For this reason, EGFR may be an attractive target for both visualization and therapy of malignant tumors using radioactive nuclides. Natural ligand of EGFR, epidermal growth factor (EGF) is a small 53-amino-acid protein. Low molecular weight of EGF may enable better intratumoral penetration in comparison to antibodies. [111In]DTPA-EGF was proposed for the targeting of glioblastoma and breast cancer, and its tumor-seeking properties were confirmed in animal studies. The aim of this study was to evaluate how the substitution of heptadentate DTPA for octadentate benzyl-DTPA (Bz-DTPA) effects the biodistribution of indium-labeled human EGF (hEGF) in normal NMRI mice. [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF, obtained by the coupling of ITC-benzyl-DTPA to hEGF, were injected into the tail vein. At 0.5, 1, 4, and 24 hours postinjection, the animals were sacrificed, and radioactivity in different organs was measured. The blood clearance of both conjugates was fast. The uptake of both conjugates in the liver, spleen, stomach, pancreas, intestines, and submaxillary gland was most likely receptor-mediated. The uptake in a majority of organs was similar. However, indium uptake in the case of [111In]DTPA-hEGF was significantly higher in the kidneys and bones. In conclusion, [111In]Bz-DTPA-hEGF seems to have more favourable in vivo distribution in comparison to [111In]DTPA-hEGF.     

Woodchuck p-glycoprotein found in virus-induced hepatocellular carcinomas binds anticancer drugs

Virally-induced hepatocellular carcinomas (HCC) are intrinsically resistant to cancer chemotherapy partly due to increased expression of p-glycoprotein (pgp). In this study, we determined that pgp expressed in woodchuck HCC had binding properties were similar to the drug resistant human pgp. Pgp drug binding properties were characterized by photoaffinity labeling with the calcium channel blocker [³H]azidopine (AZD). AZD bound pgp in HCC but not in non-tumor liver samples, and binding was confirmed by competition with Adriamycin (IC₅₀ = 10 μM) and actinomycin D (IC₅₀ = 1 μM). In summary, WHV-induced HCC overexpress a pgp which binds anticancer drugs suggesting a common pathway for drug resistance.     

Biodistribution data from 100 patients i.v. injected with 111In-DTPA-D-Phe1-octreotide

The aim of this study was to obtain accurate data on the biodistribution of ¹¹¹In-DTPA-D-Phe¹-octreotide in tumour and normal tissues to facilitate dosimetric evaluations. Patients with carcinoid tumours, medullary thyroid carcinoma (MTC), differentiated thyroid tumours, endocrine pancreatic tumour (EPT), breast carcinoma, and various other tumour types were i.v. injected with ¹¹¹In-DTPA-D-Phe-1-octreotide. Tumour and normal tissue samples were collected during surgery 1-35 days later, and the ¹¹¹In activity concentration determined. Results showed large inter- and intra-individual variations. The ¹¹¹Inconcentration was in general higher in carcinoids and some EPT (range 0.33-77% IA/kg) than in MTC and other tumours (0.017-7.8% IA/kg). Tumour-to-blood ratios (T/B) higher than 100 were found in most patients with carcinoids, EPT, renal carcinoma, and neuroendocrine carcinoma (max value 1500), while T/B was below 80 in most other tumours. Normal-tissue-to-blood ratios were in general≤10 but higher values were found in liver, kidneys, and spleen. The results presented are important for dosimetric calculations, when radiolabelled octreotide is used for diagnostic or therapeutic purposes.     

A Pet System Based on 2-18Fdg Production with a Low Energy Electrostatic Proton Accelerator and a Dual Headed Pet Scanner

We have developed a comparatively inexpensive PET system, based on a rotating scanner with two scintillation camera heads, and a nearby low energy electrostatic proton accelerator for production of short-lived radionuclides. Using a 6 MeV proton beam of 5 μA, and by optimization of the target geometry for the ¹⁸O(p, n)¹⁸F reaction, 750 MBq of 2-¹⁸FDG can be obtained. The PET scanner shows a spatial resolution of 6 mm (FWHM) and a sensitivity of 80 s^-1kBq^-1ml^-1 (3 kcps/μCi/ml). Various corrections are included in the imaging process, to compensate for spatial and temporal response variations in the detector system. Both filtered backprojection and iterative reconstruction methods are employed. Clinical studies have been performed with acquisition times of 30-40 min. The system will be used for clinical experimental research with short- as well as long-lived positron emitters. Also the possibility of true 3D reconstruction is under evaluation.