Abstract  There have been extensive studies in sheep and cattle considering cobalt (Co) supplementation and its effects on vitamin B12 concentrations in the body. However, there are limited studies on goats. The aim of this study was to compare two different sources of Co (sulfate v. glucoheptonate) at two different concentrations (0.25 and 0.5 mg/kg dry matter) in goat kid nutrition, and to evaluate the effects of these supplements on performance, serum vitamin B12, blood biochemistry and rumen volatile fatty acids. For this purpose, 30 weaned male goat kids were randomly allotted to five treatments. Serum vitamin B12 increased during the trial in the Co-supplemented groups. Co supplementation increased serum glucose concentrations. On day 35, Co-supplemented groups had greater glucose concentrations compared with control. Propionic+iso-butyric acid concentrations increased only in the 0.5 mg Co glucoheptonate treatment (P<0.05). Our results suggest that, despite the two sources of Co proving mostly similar, the main advantage of Co glucoheptonate compared with Co sulfate was in the ruminal synthesis of vitamin B12. However, although providing Co at National Research Council recommendation levels maintained vitamin B12 above or at normal concentrations, Co supplementation of the Co sufficient basal diet increased vitamin B12 and glucose concentrations.

Abstract  PURPOSE: The purpose of this study was to design and evaluate a novel platform for labelling of Affibody molecules, enabling both recombinant and synthetic production and site-specific labelling with (99m)Tc or trivalent radiometals.

METHODS: The HER2-specific Affibody molecule PEP05352 was made by peptide synthesis. The chelator sequence SECG (serine-glutamic acid-cysteine-glycine) was anchored on the C-terminal to allow (99m)Tc labelling. The cysteine can alternatively serve as a conjugation site of the chelator DOTA for indium labelling. The resulting (99m)Tc- and (111)In-labelled Affibody molecules were evaluated both in vitro and in vivo.

RESULTS: Both conjugates retained their capacity to bind to HER2 receptors in vitro and in vivo. The tumour to blood ratio in LS174T xenografts was 30 at 4 h post-injection for both conjugates. Biodistribution data showed that the (99m)Tc-labelled Affibody molecule had a fourfold lower kidney accumulation compared with the (111)In-labelled Affibody molecule while the accumulation in other organs was similar. Gamma camera imaging of the conjugates could clearly visualise the tumours 4 h after injection.

CONCLUSION: Incorporation of the C-terminal SECG sequence in Affibody molecules provides a general multifunctional platform for site-specific labelling with different nuclides (technetium, indium, gallium, cobalt or yttrium) and for a flexible production (chemical synthesis or recombinant).

Abstract  Recently, complementary DNA (cDNA) encoding a p-aminohippurate (PAH) transporter designated rat organic anion transporter 1 (OAT1) was isolated. OAT1, a multispecific organic anion transporter at the basolateral membrane, is exclusively expressed in the middle segment of the proximal tubule in the rat kidney. It has been proposed that OAT1 is indirectly involved in PAH uptake via the Na(+) dicarboxylate cotransporter. In this study, in molecular biologic experiments using OAT1-expressing Xenopus laevis oocytes, we obtained evidence that (99m)Tc-mercaptoacetylglycylglycylglycine (MAG3) is transported via OAT1. METHODS: Capped OAT1 complementary RNA (cRNA) was synthesized from library plasmid cDNA linearized with BamHI using in vitro transcription. Defolliculated oocytes were injected with 10 ng of OAT1 cRNA. Two to 3 d after injection, uptake of (99m)Tc-MAG3 was measured using ND96 solution containing 18.5 kBq of (99m)Tc-MAG3. Before the uptake experiments, OAT1-expressing oocytes were preincubated for 2 h with 1 mmol/L glutarate (a dicarboxylate), to generate an outwardly directed glutarate gradient. Then, after incubation for 60 min at room temperature, radioactivity of oocytes was determined. For the inhibition experiments, uptake was assessed in the absence or presence of inhibitor: 2 mmol/L of PAH, o-iodohippurate (OIH), probenecid, 3,5-diiodo-4-pyridone-N-acetate (iodopyracet), furosemide, ethacrynic acid, glucoheptonate, maleic acid, L-Tyr, or tetraethylammonium (TEA) or 0.1 mmol/L of 2,4-dinitrophenol (DNP). RESULTS: Na(+) had a significant effect on (99m)Tc-MAG3 uptake (P < 0.05). Accumulated glutarate stimulated simultaneous (99m)Tc-MAG3 uptake and glutarate excretion (P < 0.001). The following compounds significantly inhibited (99m)Tc-MAG3 uptake: PAH, 8.5% +/- 16.2% of (99m)Tc-MAG3 uptake in the absence of an inhibitor; OIH, 26.4% +/- 21.7%; probenecid, 29.1% +/- 12.4%; iodopyracet, 15.8% +/- 7.9%; furosemide, 30.5% +/- 15.7%; ethacrynic acid, 21.6% +/- 10.6%; glucoheptonate, 35.6% +/- 22.6%; and maleic acid, 60.1% +/- 18.7%. (99m)Tc-MAG3 accumulation in Xenopus laevis oocytes was not significantly inhibited by TEA, L-Tyr, or DNP. CONCLUSION: The following substances had a cis-inhibitory effect on (99m)Tc-MAG3 transport: PAH, OIH, probenecid, iodopyracet, furosemide, ethacrynic acid, and glucoheptonate. Glutarate had a trans-stimulative effect on (99m)Tc-MAG3 transport. (99m)Tc-MAG3 acts as a substrate of OAT1, an organic anion/dicarboxylate exchanger.

Abstract  Presents abstracts of research related to alternative medicine. "Succimer Therapy for Congenital Lead Poisoning From Maternal Petrol Sniffing," "Toxicokinetics of Mercury Elimination by Succimer in Twin Toddlers," "Plasma Clearance of Lovastatin Versus Chinese Red Yeast in Healthy Volunteers."

Abstract  The stability of cefamandole nafate injection in various parenteral solutions and with secondary additives was investigated. Solutions of cefamandole nafate injection in the following. concentrations were prepared: (1) 285 mg/ml cefamandole activity in nine intramuscular solutions; (2) 2 or 20 mg/ml; or both, in 28 intravenous solutions; (3)2 and 5 mg/ml in peritoneal dialysis fluid (PDF) concentrates with 30 and 50% dextrose; (4) 2, 20, and 100 mg/ml with tobramycin sulfate, gentamicin sulfate, calcium gluceptate, and calcium gluconate; and 0) concentrations up to 285 mg/ml with various concentrations Tof lidocaine hydrochloride. The solutions were stored at 5 and A 25 °C and evaluated visually for incompatibility. Stability of cefamandole nafate was determined periodically by polarographic or turbidimetric assay. The extent of hydrolysis of the formyl ester of cefamandole in some solutions was also studied using high-pressure liquid chromatography. Greater than 90% cefamandoie potency was retained for at least three days at 25 °C and 10 days at 5 °C in all parenteral solutions except in 2 mg/ml in 5% dextrose, 5% dextrose and 0.15% potassium chloride, 5% dextrose and 0.45% sodium chloride, Plasma-Lyte, and 0.9% sodium chloride injections. Visual incompatibilities were observed in acetated Ringer's, 5% dextrose and 0.15% potassium chloride, lonosol B in 5% dextrose, Isolyte E with 5% dextrose, Isolyte M with 5% dextrose, Plasma-Lyte, Ringer's, and lactated Ringer's injections. Cefamandoie nafate was incompatible with all secondary additives except with certain concentrations of lidocaine hydrochloride. Cefamandoie nafate 2 mg/ml was compatible with the PDF concentrates for 24 hours at 25 °C. The dextrose content and the pHdf the parenteral solutions influenced the rate and extent of hydrolysis of the formyl ester of cefamandole. Cefamandole nafate was stable and compatible in 11 of the 37 parenteral solutions studied for at least three days at 25 °C and. 10 days at 5 °C. Considering the potential for microbial growth, however, storage limits of 24 and 96 hours at 25 and 5 °C, respectively, are recommended.

Abstract  We compared the maximal calcitonin secretion produced by pentagastrin, calcium, and glucagon for preoperative detection of medullary thyroid carcinoma in four subjects with normal or slightly increased plasma immunoreactive calcitonin (iCT) levels. In each case, pentagastrin administration produced higher peak iCT levels (5- to 36-fold increases over basal) than did calcium infusion (by 1.9- to 10.3-fold) and glucagon administration (by 3.6- to 27.4-fold). These preliminary studies suggest that pentagastrin is an effective agent for use in rapid stimulation tests designed to detectmedullary thyroid carcinoma in asymptomatic patients who have normal basal iCT concentrations.

Abstract  IPA COPYRIGHT: ASHP Surface recrystallization and changes in the matrix of the compact were examined by scanning electron microscopy following compaction of directly compressible aspirin, anhydrous calcium gluceptate, ferrous sulfate, metoclopramide HCl, methenamine and sucrose and storage of the compacts at 25DGC and 0 or 43% relative humidity. Crystal growth and surface restructuring were observed for all compounds, with particularly dramatic growth rates for aspirin, calcium gluceptate and metoclopramide.

Abstract  [99mTc]Technetium[2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1] oct-2-yl]-methyl] (2-mercaptoethyl) amino] ethyl] amino] ethane-thiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)] ([99mTc] TRODAT-1) is a useful imaging agent for central nervous system dopamine transporters. The purpose of this study was to characterize the in vivo binding potential and kinetic rate constants of this agent in nonhuman primates. A series of four SPECT scans were performed on each of two female baboons with a bolus injection of [99mTc]TRODAT-1 (717+/-78 MBq; 19.38+/-2.12 mCi). Dynamic images of the brain were acquired over 4 h using a triple-head camera equipped with fan-beam collimators. Arterial and venous blood were sampled frequently using a peristaltic pump throughout the duration of the study. Regions of interest were drawn on the corresponding MRI scan to which each functional image was coregistered. Using analytical solutions to the three-compartment model with the Levenberg-Marquardt minimization technique, each study was individually fitted to a kinetic parameter vector (method I). Additionally, within each subject, three corresponding intrasubject studies were fitted simultaneously to a single parameter vector by constraining the binding potential, distribution volume and dissociation rate constant to improve the identifiability of the parameter estimates (method II). The results clearly indicated that [99mTc] TRODAT-1 localized in the striatum with slower washout rate than other brain regions. A maximal target/nontarget ratio of 3.5 between striatum and cerebellum was obtained. SPECT image analysis of the striatum yielded unconstrained k3/k4 values of 3.4+/-1.4, 2.4+/-0.7, 3.0+/-1.5, and 4.0+/-10.3, with respective constrained (fixed k4) values of 2.9 +/- 0.4, 2.4 +/- 0.4, 1.7+/-0.4 and 1.8+/-0.4 in one baboon using method I. With method II, the corresponding simultaneously fitted values were 2.1+/-0.3 using no constraints and 2.2+/-0.2 using a fixed k4. The second baboon had similar results. These findings suggest that the binding potential and corresponding kinetic rate constants can be reliably estimated in nonhuman primates with dynamic SPECT imaging of the dopamine transporter using a technetium-based tropane analogue. Furthermore, method II parameter vectors compare favorably to those produced using method I based on SEEs.

Abstract    The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4- or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

Abstract  Two kinds of novel thymidine derivatives, N-thymidine-yl-N′-methyl-N′-{N′′-[2-sulfanyl-(ethylamino)acetyl]-2-aminoethylsulfanyl-1-hexanamide}-ethanediamine (TMHEA) and N-thymidine-yl-N′-methyl-N′-{N′′-[2-sulfanyl-(ethylamino)acetyl]-2-aminoethylsulfanyl-1-hexanamide}-hexanediamine (TMHHA) were prepared and successfully labeled with (99m)Tc in high labeling yields. The in vitro stability and in vivo biodistribution of (99m)Tc-TMHEA and (99m)Tc-TMHHA were investigated and compared. The biodistribution studies indicate that the radiotracer (99m)Tc-TMHEA displays selective tumor uptake, suggesting it is a potential tumor imaging agent.

Abstract  Mitomycin C (MMC) has been used as a component of many chemotherapeutic regimens and some toxic effects of this substance have been reported. As it has been reported that the toxicological effect of a drug can alter the biodistribution of radiopharmaceuticals and because patients on chemotherapeutic treatment can be submitted to a nuclear medicine procedure, we investigated whether MMC could affect the uptake of various technetium-99m (99mTc) radiopharmaceuticals used for renal evaluations. The purpose of this study was to suggest a model to evaluate the toxic effect of substances in specific organs. Three doses of MMC (0.45 mg) were administered to mice (N=15). One hour after the last dose, 99mTc radiopharmaceuticals, 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA) or 99mTc-glucoheptonic acid (99mTc-GHA), with activity of 7.4 MBq, were also administered in the treated group and in the control group (N=15). After another 0.5 h, the animals were sacrificed. The organs were isolated, the 99mTc radiopharmaceutical uptake in the organs quantified in a well counter and the percentages of radioactivity (%ATI) calculated. The results have shown that: (i) with 99mTc-DTPA, the %ATI increased in the pancreas, ovary, uterus, stomach, kidney, spleen, thymus, heart, lung, liver, thyroid and bone; (ii) with 99mTc-DMSA, the %ATI decreased in all the organs except for the brain; and (iii) with 99mTc-GHA, the %ATI increased in the liver and decreased in the stomach, thymus, heart and thyroid. The effects of this chemotherapeutic drug on the biodistribution of these radiopharmaceuticals were statistically significant (Wilcoxon test, p<0.05) and could be explained by the metabolization and/or therapeutic action of MMC. Studies with other radiopharmaceuticals are in progress.

Abstract    Issue Title: Abstracts of the Annual Congress of the EANM 2008, Munich, Germany

Abstract  Objective: To assess the trends in prescription drugs and the potential repercussions to newborns among pregnant women who attended prenatal consultations and gave birth in the Department of Gynaecology of Tokoin’s University Hospital, Lome (Togo). Methods: A retrospective study of the registers of prenatal visits and deliveries of the eligible population was performed. Results: In total, 184 different drugs were prescribed to 627 pregnant women attending prenatal consultations. The profile of pharmacotherapeutic groups prescribed was: anti-anaemics (33.33%), antimalarial drugs (24.75%), vitamins ± mineral salts, amino acids and appetite stimulants (14.96%) and antispasmodics and anti-emetics (7.22%). The median proportion of prescriptions for each pharmacotherapeutic group increased significantly from the first to third trimester (9.72, 25.17 and 64.00 respectively; P < 0.05). The median number of drugs prescribed did not vary significantly (P = 0.051) with the age groups, parity (P = 0.068) or obstetrical–gynaecological history (P = 0.401); it did, however, increase significantly with the medical–surgical history (P < 0.05). There were complications associated with deliveries that had no obvious cause related to drug prescription, including four cases of minor defects, 28 stillborns, 65 cases of low birth weight and 27 hospitalised newborns for neonatal diseases. Some interventions were needed for safeguarding the health of the mother, the foetus and the newborn. Conclusion: The trends in obtaining prescription drugs and the consumption of drugs by pregnant women can be assessed using multiple parameters. We limited our study to age groups, gestational age, parity and the medical history of the pregnant woman, profile of pharmacotherapeutic groups, median number of drugs prescribed and the potential risks of the drugs used. The results of our retrospective study were not alarming in terms of neonatal outcomes.

Abstract  Chemotactic peptides have been proposed as vehicles to image infection and inflammation. Previous studies have shown high uptake at the site of infection soon after injection, most likely because of specific binding to receptors on locally present leukocytes. To investigate this hypothesis, the in vivo behavior of a synthetic chemotactic peptide was compared to a control peptide of similar molecular weight with low receptor binding affinity. In addition, the potential to target to different infections and sterile inflammation was tested. Twenty-four hours after induction of Escherichia coli, Staphylococcus aureus and zymosan abscesses, rabbits were i.v. injected with either 1 mCi of 99mTc-labeled formyl-methionyl-leucyl-phenylalanyl-lysine-hydrazinonicotinamid e (99mTc-fMLFK-HYNIC) or 99mTc-labeled hydrazinonicotinamide-methionyl-leucyl-phenylalanyl-OMe (99mTc-HYNIC-MLFOMe, control peptide). Gamma camera images were obtained at 5 min and 1, 4, 8 and 20 hr postinjection. Biodistribution was determined at 20 hr postinjection. The blood clearances of 99mTc-fMLFK-HYNIC and 99mTc-HYNIC-MLFOMe were similar. With time, 99mTc-fMLFK-HYNIC was retained in the abscess (E. coli), whereas the control agent 99mTc-HYNIC-MLFOMe was cleared from the abscess (0.049 +/- 0.011 versus 0.005 +/- 0.0003% 1D/g at 20 hr postinjection; p < 0.0005). Abscess-to-contralateral muscle ratios of 99mTc-fMLFK-HYNIC rose to 36.8 +/- 4.3 at 20 hr postinjection. E. coli, S. aureus and zymosan abscesses were clearly visualized from 4 hr postinjection onward. Abscess-to-background ratios increased to values varying from 4.4 +/- 0.2 (zymosan) to 7.1 +/- 0.6 (S. aureus) at 20 hr postinjection. The uptake in S. aureus and zymosan abscesses did not differ significantly from the uptake in E. coli abscesses. fMLFK-HYNIC is retained in both acute infection and sterile inflammation by means of specific receptor binding if sufficient cellular infiltration is present.

Abstract  The mangrove crab Ucides cordatus is a bioindicator of aquatic contamination. In this work, the iron availability and redox activity of saccharide-coated mineral iron supplements (for both human and veterinary use) and ferrocene derivatives in Saline Ucides Buffer (SUB) medium were assessed. The transport of these metallodrugs by four different hepatopancreatic cell types (embryonic (E), resorptive (R), fibrillar (F), and blister (B)) of U. cordatus were measured. Organic coated iron minerals (iron supplements) were stable against strong chelators (calcein and transferrin). Ascorbic acid efficiently mediated the release of iron only from ferrocene compounds, leading to redox-active species. Ferrous iron and iron supplements were efficient in loading iron to all hepatopancreatic cell types. In contrast, ferrocene derivatives were loaded only in F and B cell types. Acute exposition to the iron compounds resulted in cell viability of 70-95%, and to intracellular iron levels as high as 0.40 μmol L-1 depending upon the compound and the cell line. The easiness that iron from iron metallodrugs was loaded/transported into U. cordatus hepatopancreatic cells reinforces a cautionary approach to the widespread disposal and use of highly bioavailable iron species as far as the long-term environmental welfare is concerned.

Abstract  PURPOSE: To review early recommendations and propose guidelines for breastfeeding interruption after administration of radiopharmaceuticals, based on additional biokinetic and dosimetric data.

METHODS: Activity concentrations in breast milk from 53 breastfeeding patients were determined. The milk was collected at various times after administration of 16 different radiopharmaceuticals. The fraction of the activity administered to the mother excreted in the breast milk, the absorbed doses to various organs and tissues and the effective dose to the infant were estimated.

RESULTS: The fraction of the administered activity excreted per millilitre of milk varied widely from 10(-10) to 10(-3) MBq/MBq administered. For (99m)Tc-labelled radiopharmaceuticals, the total fraction of the administered activity excreted in the milk varied from 0.0057 % for (99m)Tc-labelled red blood cells (RBC) to 19 % for (99m)Tc-pertechnetate. The effective dose to an infant per unit activity administered to the mother ranged from 6.7 × 10(-6) mSv/MBq for (99m)Tc-labelled RBC to 3.6 × 10(-2) mSv/MBq for (99m)Tc-pertechnetate. For the other radiopharmaceuticals, the total fraction of administered activity excreted in the milk varied from 0.018 % ((51)Cr-EDTA) to 48 % ((131)I-NaI). The effective dose ranged from 5.6 × 10(-5) mSvinfant/MBqmother ((51)Cr-EDTA) to 106 mSvinfant/MBqmother ((131)I-NaI).

CONCLUSIONS: Based on an effective dose limit of 1 mSv to the infant and a typical administered activity, we recommend cessation of breastfeeding for (131)I-NaI and interruption of feeding for 12 h for (125)I-iodohippurate, (131)I-iodohippurate, (99m)Tc-pertechnetate and (99m)Tc-MAA. During this 12-h period all breast milk should be expressed at least three times and discarded. For the other radiopharmaceuticals included in this study, no interruption of breastfeeding is necessary.

Abstract  PurposeThe Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.MethodsThe SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary, or sooner, if indicated.ConclusionEach practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by entities not providing these services is not authorized.

Abstract  The usual means of assessing the health of newly received beef cattle susceptible to bovine respiratory disease (BRD) are subjective, typically involving visual evaluation aided by minimal clinical measurements. Recent evidence based on the occurrence of pneumonic lung lesions at slaughter indicates a need for more accurate methods of diagnosing BRD. Inadequate passive immune transfer at birth may be an important risk factor in susceptibility to BRD, suggesting the need for management to improve passive transfer success rates. Preweaning management and vaccination practices offer opportunities for beef cattle producers to improve the immune status of newly weaned calves and decrease postweaning BRD. Feeding diets with higher levels of concentrate typically improves performance by newly weaned or received cattle, as does feeding diets supplemented with protein; however, limited data suggest that increasing concentrate and protein in receiving diets increases the rate and severity of subjectively determined BRD morbidity. Research with receiving diet concentrate/protein level relative to humoral and cell-mediated immune function coupled with indicators of health and performance is needed. Supplemental B vitamins are sometimes useful in receiving diets, but the effects have been variable, presumably reflecting differences in stress and associated feed intake responses. Vitamin E added to receiving diets to supply > or = 400 IU/animal daily seems beneficial for increasing gain and decreasing BRD morbidity; however, further dose titration experiments are needed. Supplemental Zn, Cu, Se, and Cr can alter immune function of newly received calves, and some field trials have shown decreases in BRD morbidity rate with supplementation; however, several experiments have shown no performance or health/immune benefits from supplementation of these trace minerals. Formulation of receiving diets should take into account decreased feed intake by highly stressed, newly received beef cattle and known nutrient deficiencies, but fortification of such diets with trace minerals beyond the levels needed to compensate for these effects is difficult to justify from present data.

Abstract  After several decades of debate, it is now widely acknowledged that apoptosis, also known as programmed cell death, is central to homoeostasis and normal development and physiology in all multicellular organisms, including humans. The dysregulation of apoptosis can lead to the destruction of normal tissues in a variety of disorders, including autoimmune and neurodegenerative diseases (too much apoptosis) or the growth of tumors (too little apoptosis). In addition, effective therapy of tumors requires the iatrogenic induction of programmed cell death by radiation, chemotherapy, or both. Given the central role of apoptosis, it would be desirable to have a noninvasive imaging method to serially detect and monitor this process in cancer patients undergoing conventional radiation and chemotherapy treatments as well as for the development and testing of new drugs. In this article, the latest modalities and contrast agents described in the literature for the imaging of apoptosis in vivo are reviewed. First, the most recent developments in the biochemical characterization of the many intracellular pathways involved in this complex process are discussed. Next, a variety of new radionuclide tracers, including radiolabeled annexin V and caspase inhibitors for PET and SPECT, are described. Finally, the use of MRI, MR spectroscopy, and ultrasound as possible alternative imaging modalities for the imaging of apoptosis is addressed. [PUBLICATION ABSTRACT] After several decades of debate, it is now widely acknowledged that apoptosis, also known as programmed cell death, is central to homoeostasis and normal development and physiology in all multicellular organisms, including humans. The dysregulation of apoptosis can lead to the destruction of normal tissues in a variety of disorders, including autoimmune and neurodegenerative diseases (too much apoptosis) or the growth of tumors (too little apoptosis). In addition, effective therapy of tumors requires the iatrogenic induction of programmed cell death by radiation, chemotherapy, or both. Given the central role of apoptosis, it would be desirable to have a noninvasive imaging method to serially detect and monitor this process in cancer patients undergoing conventional radiation and chemotherapy treatments as well as for the development and testing of new drugs. In this article, the latest modalities and contrast agents described in the literature for the imaging of apoptosis in vivo are reviewed. First, the most recent developments in the biochemical characterization of the many intracellular pathways involved in this complex process are discussed. Next, a variety of new radionuclide tracers, including radiolabeled annexin V and caspase inhibitors for PET and SPECT, are described. Finally, the use of MRI, MR spectroscopy, and ultrasound as possible alternative imaging modalities for the imaging of apoptosis is addressed.

Abstract  The early assessment of a solid tumor's response to conventional or new drug therapy to complement or replace current RECIST (or other clinical) criteria remains an elusive goal. The work horse PET tracer 18 F-FDG, may represent the most immediate method to track individual tumor response to therapy for many types of cancer. Newer radiotracers such as radiolabeled annexin V, have also shown the ability to selectively localize to tumor cells undergoing apoptosis (programmed cell death) in response to successful treatment in vivo. In this article we will review therapy reduced tumor apoptosis and the radiotracers used to date to image this process in both animal models and clinical trials.