Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities.

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [99mTc]Tc-Sestamibi, [99mTc]Tc-Tetrofosmin, and [99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [99mTc]Tc-Sestamibi and [99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in 99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.

Optimization of newly developed and lead shields thicknesses for protecting taxi drivers from 99mTc injected patients.

Presently, public members are exposed to sources of ionizing radiation, and health risks due to radiation exposures should be a concern. This study aims to calculate the whole-body cumulative radiation exposure of taxi drivers. Also, this study will provide the effect of using a simple lead shield and three types of glass shield AVT6, TZN-D, and SLGC-E5, by calculating the effective annual dose of the taxi drivers that work in medical centers. Two MIRD phantoms as a driver and patient, a sample body of a taxi, pure lead, and glass sheets as a shield, were simulated using the MCNP code. We assumed that the patients had undergone the brain, liver, and kidney SPECT imaging by injecting 99mTC-HMPAO, 99mTC-sulfur colloid, and 99mTC-DMSA with the activity of 740MBq, 185MBq, and 333MBq, respectively. These shields are simulated on two sides of the driver, in the back and right side. The annual effective dose was calculated for 0-3.5 g/cm2 area densities. It was observed that the 0.45, 1.09, 1.28, and 2.11 g/cm2 of Pb, TZN-D, AVT6, and SLGC-E5 respectively decrease the effective dose below the allowed limit. According to the results, using the lead shield, the effective dose was reduced by a factor up to 7.25 times. It is recommended that taxi drivers wear a 0.4 mm lead shield or its equivalent when they have Tc-99 m injected patients.

Influence of single photon emission computed tomography (SPECT) reconstruction algorithm on diagnostic accuracy of parathyroid scintigraphy: Comparison of iterative reconstruction with filtered backprojection.

BACKGROUND & OBJECTIVES: Preoperative localization of parathyroid lesions is essential for improving the results in patients with primary hyperparathyroidism. The purpose of this study was to evaluate retrospectively the value of technetium-99m (Tc-99m) methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) and to compare the diagnostic accuracy of iterative reconstruction (IR) and filtered backprojection (FBP) reconstruction algorithms about localization of parathyroid lesions. METHODS: Forty four patients with primary hyperparathyroidism, in whom histopathological correlation could be performed, were included in the study. Dual-phase Tc-99m parathyroid scintigraphy was performed 20 and 120 min after injection of 740 MBq Tc-99m MIBI in all patients. Tomographic images were acquired 120 min after the administration of radiopharmaceutical. The SPECT data were evaluated using an IR as well as a FBP algorithm. In 23 of 44 patients, SPECT acquisitions were performed in 64×64 matrix; in the remaining 21 patients, tomographic data were collected in 128×128 matrix. The imaging results were compared with pathological findings and sensitivities of both reconstruction algorithms, and planar views were calculated. RESULTS: Using planar MIBI scans, abnormal parathyroid glands were correctly localized in 75 per cent of the cases. Sensitivity increased to 77 per cent using SPECT with FBP and to 84 per cent with IR. When the sensitivities were calculated according to the acquisition matrix, these were 95 per cent (20/21) and 85 per cent (18/21) for IR and FBP, respectively in patients in whom 128×128 matrix was used. The sensitivities were lower in patients who were imaged with 64×64 matrix; these were calculated as 74 per cent (17/23) and 70 per cent (16/23) with IR and FBP, respectively. INTERPRETATION & CONCLUSIONS: Our findings showed that compared to planar scintigraphy, Tc-99m MIBI SPECT was more sensitive diagnostic modality in the detection of abnormal parathyroid tissues. Image quality and sensitivity may be improved further when larger matrices with IR are used instead of FBP algorithm.

The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer.

The prostate-specific membrane antigen (PSMA) has received increased consideration during the past few years as an excellent target for both imaging and therapy of prostate cancer. After many years of outstanding preclinical research, the first significant step forward in clinical use was achieved in 2008 with the first human experience with the small-molecule PSMA inhibitors 123I-MIP-1972 and 123I-MIP-1095. A clinical breakthrough followed in 2011 with 68Ga-PSMA-11 for PET imaging and 131I-MIP-1095 for endoradiotherapy of metastatic prostate cancer. Since then, PET/CT with 68Ga-PSMA-11 has rapidly spread worldwide, and endoradiotherapy with PSMA ligands has been conducted at increasing numbers of centers. 68Ga-PSMA-11 is currently the subject of multicenter studies in different countries. Since 2013, 131I-related PSMA therapy has been replaced by 177Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter studies. Alternative PSMA ligands for both imaging and therapy are available. Among them is 99mTc-MIP-1404, which has recently entered a phase 3 clinical trial. This article focuses on the highlights of the development and clinical application of PSMA ligands.

Radioactive probe-guided parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: The value of gamma probes in the surgical treatment of secondary hyperparathyroidism (sHPT) was determined. METHOD: We retrospectively analyzed the clinical data of 48 sHPT patients between May 2007 and September 2011. Preoperative (99)Tc(m)- methoxyisobutyl isonitrile (MIBI) scintigraphy and high-frequency ultrasonography were used for parathyroid localization. Thirty-five patients (group I) underwent conventional neck exploration and open parathyroidectomy. Thirteen patients (group II) underwent gamma probe-guided total parathyroidectomy and parathyroid transplantation. The two groups were compared in terms of the number of parathyroid resections, operative time, and postoperative changes in the blood levels of parathyroid hormone (PTH), calcium, and phosphate. RESULTS: The clinical manifestations, PTH and calcium levels, age distribution, and clinical characteristics did not differ between the two groups. The accuracy of preoperative (99)Tc(m)-MIBI scintigraphy (89.74%) for the diagnosis of hyperparathyroidism did not differ from that of ultrasonography (81.25%). However, the accuracy of (99)Tc(m)-MIBI scintigraphy (66.67%) for localizing hyperfunctioning parathyroids was significantly lower than that of ultrasonography (76.86%). The operation time was significantly longer in group I (120+/-25) min than in group II (90+/-30) min. The accuracy of parathyroid specimens were obtained in group I (2.5+/-0.5) than in group II (3.5+/-0.5). Compared with group I, group II showed a significant increase (15.4%) in the number of parathyroid resections. The PTH, calcium, and phosphate levels significantly decreased postoperatively in all patients. CONCLUSION: Intraoperative gamma probe examination confirmed that the excised specimen was parathyroid tissue and improved the accuracy of parathyroid resection. The parathyroidectomy rate was increased by 15.4% due to the use of these probes. However, the probes did not detect all ectopic parathyroids, and further research is required to clarify the underlying reasons.

Radioactive probe-guided parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: The value of gamma probes in the surgical treatment of secondary hyperparathyroidism (sHPT) was determined. The aim of this study was to enhance the rate of successful total parathyroidectomy in patients with sHPT using intraoperative gamma probe investigations. METHODS: We retrospectively analyzed the clinical data of 48 sHPT patients between May 2007 and September 2011. Preoperative (99)Tc(m)- methoxyisobutyl isonitrile (MIBI) scintigraphy and high-frequency ultrasonography were used for parathyroid localization. Thirty-five patients (group I) underwent conventional neck exploration and open parathyroidectomy. Thirteen patients (group II) underwent gamma probe-guided total parathyroidectomy and parathyroid transplantation. The two groups were compared in terms of the number of parathyroid resections, operative time, and postoperative changes in the blood levels of parathyroid hormone (PTH), calcium, and phosphate. RESULTS: The clinical manifestations, PTH and calcium levels, age distribution, and clinical characteristics did not differ between the two groups. The accuracy of preoperative (99)Tc(m)-MIBI scintigraphy (89.74%) for the diagnosis of hyperparathyroidism did not differ from that of ultrasonography (81.25%). However, the accuracy of (99)Tc(m)-MIBI scintigraphy (66.67%) for localizing hyperfunctioning parathyroids was significantly lower than that of ultrasonography (76.86%). The operation time was significantly longer in group I ((120 ± 25) minutes) than in group II ((90 ± 30) minutes). The accuracy of parathyroid identification was significantly higher in group II (92.59%) than in group I (80.39%). On average, significantly fewer parathyroid specimens were obtained in group I (2.5 ± 0.5) than in group II (3.5 ± 0.5). Compared with group I, group II showed a significant increase (15.4%) in the number of parathyroid resections. The PTH, calcium, and phosphate levels significantly decreased postoperatively in all patients. CONCLUSIONS: Intraoperative gamma probe examination confirmed that the excised specimen was parathyroid tissue and improved the accuracy of parathyroid resection. The parathyroidectomy rate was increased by 15.4% due to the use of these probes. However, the probes did not detect all ectopic parathyroids, and further research is required to clarify the underlying reasons.

Synthesis, characterization, and biological evaluation of (99m) Tc(CO)3 -labeled peptides for potential use as tumor targeted radiopharmaceuticals.

During the past decade, several peptides containing Arg-Gly-Asp sequence have been conjugated with different chelating agents for labeling with various radionuclides for the diagnosis of tumor development. In this study, we report the synthesis of two tetrapeptides (Asp-Gly-Arg-His and Asp-Gly-Arg-Cys) and one hexapeptide [Asp-Gly-Arg-D-Tyr-Lys-His] by changing the amino acid sequence of the Arg-Gly-Asp motif. Peptide synthesis was initiated from aspartic acid. Aspartic acid placed at C-terminal end of the peptide chain can be conjugated with different drug molecules facilitating their transport to the site of action. The peptides were synthesized in excellent yield and labeled using freshly prepared [(99m) Tc(CO)3 (H2 O)3 ](+) intermediate. A complexation yield of over 97% was achieved under mild conditions even at low ligand concentrations of 10(-2)  m. Radiolabeled peptides were characterized by HPLC and were found to be substantially stable in saline, in His solution as well as in rat serum and tissue (kidney, liver) homogenates. Internalization studies using Ehrlich ascites carcinoma cell line showed rapid and significant internalization (30-35% at 30 min of incubation attaining maximum value of about 40-60% after 2-4 h incubation). A good percentage of quick internalization was also observed in αv ß3 -receptor-positive B16F10 mouse melanoma cell line (14-16% after 30 min of incubation and 25-30% after 2-4 h incubation). Imaging and biodistribution studies were performed in Swiss albino mice bearing Ehrlich ascites tumor in right thigh. Radiolabeled peptides exhibited fast blood clearance and rapid elimination through the urinary systems. (99m) Tc(CO)3 -tetra-Pep2 exhibited remarkable localization at tumor site (1.15%, 1.17%, and 1.37% ID/g at 2, 4, and 6 h p.i., respectively) which could be due to slow clearance of the radiolabeled peptide from blood in comparison with the other two radiolabeled peptides. However, (99m) Tc(CO)3 -hexa-Pep exhibited the highest tumor to muscle and tumor to blood ratios among the three. The preliminary results with these amino acid-based peptides are encouraging enough to carry out further experiments for targeting tumor.

An investigation of the early detection of radiation induced apoptosis by 99mTc-Annexin V and 201thallium-chloride in a lung cancer cell line.

This study aims to investigate the efficacy of in vitro Thallium-201 Chloride (Tl-201) and in vitro and in vivo Tc-99m HYNIC-coupled Annexin V (TAV) in the early detection of radiation induced apoptosis, a proxy indicator of radiation therapy (RT) efficacy. In vitro Tl-201 and TAV accumulation and efflux in non-small cell lung cancer were measured post irradiation at 5 different gamma ray doses. The replication rates (RR) of the cell lines were also measured. The same non-small cell lung cancer line was inoculated into the left femur. In vivo non-invasive Tl-201 and TAV tracer biodistribution studies were performed. Cell RR decrease with increased radiation dose was observed 48 hours after irradiation. Apoptotic cell number was found to have increased in response to 9 Gy and 12 Gy radiation dose. Tl-201 accumulation in the 9 Gy and 12 Gy irradiation groups was found to be higher than the lower irradiation groups. Quick Tl-201 efflux was observed in the 9 Gy and 12 Gy irradiated cells. At 48 hours after irradiation with 9 Gy and 12 Gy, Annexin V accumulation was found to be higher than in the control and 3-6 Gy groups. In vivo mouse model confirmed the increased TAV uptake in implanted tumors for relatively high 9 Gy irradiation as compared to non-irradiated controls. TAV may prove to be an effective radiotracer for early assessment of radiation therapy efficacy, via apoptosis, in human lung cancers.

Technetium-99m-labeled ceftizoxime loaded long-circulating and pH-sensitive liposomes used to identify osteomyelitis.

Osteomyelitis is an infectious disease located in the bone or bone marrow. Long-circulating and pH-sensitive liposomes containing a technetium-99m-labeled antibiotic, ceftizoxime, (SpHL-(99m)Tc-CF) were developed to identify osteomyelitis foci. Biodistribution studies and scintigraphic images of bone infection or non infection-bearing rats that had been treated with these liposomes were performed. A high accumulation in infectious foci and high values in the target-non target ratio could be observed. These results indicate the potential of SpHL-(99m)Tc-CF as a potential agent for the diagnosis of bone infections.

(99m)Tc(CO)(3)-Ibritumomab tiuxetan; a novel radioimmunoimaging (RII) agent of B cell non-Hodgkin's lymphoma (NHL).

To exploit the B-lymphocyte antigen-CD20 binding capacity of the Ibritumomab tiuxetan (IBTN) monoclonal antibody (mAb) for imaging, the over-expression of B cells in non-Hodgkin's lymphoma (NHL) (a myeloproliferative disorder of the lymphatic system) was investigated. In the current investigation, we present the labeling of the IBTN with technetium-99m ((99m)Tc) through [(99m)Tc(CO)(3)](+) precursor for radioimmunoimaging (RII) of the tumor prior to its treatment with (90)Y labeled IBTN. Labeled IBTN was radiobiologically characterized in terms of radiochemical purity, in vitro stability in human plasma, immunoreactivity, binding with Raji and Ramos cells and biodistribution in a female nude mouse (FNM) model. It was observed that the reduced IBTN (rIBTN) showed more promising radiobiologic characteristics than the nonreduced IBTN. Significantly higher transchelation was seen in excess cysteine compared with histidine. The radioconjugate showed higher saturated binding affinity with CD20 antigen. Significantly higher target (tumor) to background ratios were observed 1 h post-injection (p.i.). Based on radiochemical purity, in vitro stability, immunoreactivity, binding and biodistrubtion in the FNM model, we recommend the radiolabeling of the rIBTN using tricarbonyl technique as a potential RII agent.

Radiosynthesis and biological evaluation of the (99m)Tc-tricarbonyl moxifloxacin dithiocarbamate complex as a potential Staphylococcus aureus infection radiotracer.

In the present investigation, radiosynthesis of the (99m)Tc-tricarbonyl moxifloxacin dithiocarbamate complex ((99m)Tc(CO)(3)-MXND) and its biological evaluation in male Wister rats (MWR) artificially infected with Staphylococcus aureus (S. aureus) was assessed. The (99m)Tc(CO)(3)-MXND complex was radiochemically examined in terms of stability in saline and in serum and biologically its in-vitro binding with S. aureus and percent absorption in MWR models. Radiochemically the (99m)Tc(CO)(3)-MXND complex showed more than 90% stability in saline up to 240 min and in serum 14.95% undesirable species was appeared within 16h. In-vitro the (99m)Tc(CO)(3)-MXND complex showed saturated binding with S. aureus. In MWR artificially infected with live S. aureus the complex showed about six fold higher uptakes in the infected muscle as compared to the normal muscle. However, insignificant change in the uptake of (99m)Tc(CO)(3)-MXND complex in the infected and inflamed or normal muscle was observed in the MWR infected with heat killed S. aureus. The (99m)Tc(CO)(3)-MXND complex disappeared from the circulatory system and appeared in the urinary system within 60-90 min followed by excretion through normal route of urinary system. Based on the elevated and stable radiochemical succumb in saline, serum, saturated in-vitro binding with S. aureus and higher accumulation in the target organ of the MWR, we recommend the (99m)Tc(CO)(3)-MXND complex for radio-localization of the infection induced by S. aureus in human.

Preclinical evaluation of DO3P-AME-DO3P: a polyazamacrocyclic methylene phosphonate for diagnosis and therapy of skeletal metastases.

A phosphonate derivative 10'-bis(acetamido)-ethane-bis[1,4,7-tri(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane] (DO3P-AME-DO3P), was synthesized with 90% yield in high purity. It was labeled with (99m)Tc in 97.5% efficiency and specific activity of 112-250 MBq/µmol. The binding affinity of (99m)Tc-DO3P-AME-DO3P towards bone minerals was tested in vitro by using hydroxy apatite as a bone model with absorption of 93% during the first hour of the experiment. Receptor binding assay on human bone cell line SAOS-2 demonstrated K(d) value of 1.07 nM. Cell binding studies of DO3P-AME-DO3P on osteoblasts and osteoclasts cells performed in vitro displayed preferential affinity of the compound towards osteoclast (167.95 ± 3.56% dose/mg protein). The serum stability of (99m)Tc complex was found to be 96.8% after 24 h. Blood kinetics of (99m)Tc-DO3P-AME-DO3P performed on normal rabbits showed fast clearance with t(1/2)(F) = 15 min ± 0.014 min and t(1/2)(S) = 4 h 3 min ± 0.09 min. Biodistribution studies carried out in normal BALB/c mice showed bone-to-blood ratio of 20 and bone-to-muscle ratio of 33. The bone tissue demonstrated highest concentration of bound radioactivity with 10.73% ID/g at 1 h post injection. The protonation and stability constants were determined by pH-potentiometry titrations. The stability constants of DO3P-AME-DO3P with Lu(III), Sm(III), and Ho(III) were 19.7, 21.8, and 20.2 determined by "out of cell" method. The excellent bone seeking properties of DO3P-AME-DO3P make it a candidate of choice for SPECT imaging and preferential uptake of the compound in osteoclasts in comparison to osteoblasts; BMM and BMC can be used to understand the pathway of pathogenesis of osteoporosis and skeletal metastases.

Evaluating 99mTc Auger electrons for targeted tumor radiotherapy by computational methods.

PURPOSE: Technetium-99m (99mTc) has been widely used as an imaging agent but only recently has been considered for therapeutic applications. This study aims to analyze the potential use of 99mTc Auger electrons for targeted tumor radiotherapy by evaluating the DNA damage and its probability of correct repair and by studying the cellular kinetics, following 99mTc Auger electron irradiation in comparison to iodine-131 (131I) beta minus particles and astatine-211 (211At) alpha particle irradiation. METHODS: Computational models were used to estimate the yield of DNA damage (fast Monte Carlo damage algorithm), the probability of correct repair (Monte Carlo excision repair algorithm), and cell kinetic effects (virtual cell radiobiology algorithm) after irradiation with the selected particles. RESULTS: The results obtained with the algorithms used suggested that 99mTc CKMMX (all M-shell Coster-Kroning--CK--and super-CK transitions) electrons and Auger MXY (all M-shell Auger transitions) have a therapeutic potential comparable to high linear energy transfer 211At alpha particles and higher than 131I beta minus particles. All the other 99mTc electrons had a therapeutic potential similar to 131I beta minus particles. CONCLUSIONS: 99mTc CKMMX electrons and Auger MXY presented a higher probability to induce apoptosis than 131I beta minus particles and a probability similar to 211At alpha particles. Based on the results here, 99mTc CKMMX electrons and Auger MXY are useful electrons for targeted tumor radiotherapy.

Olmesartan, an angiotensin II receptor blocker, restores cerebral hypoperfusion in elderly patients with hypertension.

We evaluated the effects of olmesartan, an angiotensin II receptor blocker (ARB), on cerebral blood flow (CBF) in elderly and hypertensive subjects. Ten subjects with first- or second-degree essential hypertension (mean age, 70.5 years) underwent brain single-photon emission tomography (SPECT) scanning with (99m)Tc-ethyl cysteinate dimer before and after a 24-week course of olmesartan. Mean systolic blood pressure (SBP) was 156.2+/-9.9 mm Hg, and mean diastolic blood pressure (DBP) was 89.1+/-5.5mm Hg. No subject had any abnormalities on neurologic examination or previous history of stroke or cardiovascular disease. Before olmesartan administration, the hypertensive subjects had approximately 15% less whole brain CBF compared with age-matched normotensive controls. Regional CBF was decreased by 11%-20% in the frontal, parietal, temporal, and posterior lobes. Olmesartan treatment significantly decreased SBP to 130.4+/-4.2mm Hg (P < .001) and DBP to 78.2+/-7.0mm Hg (P < .001). After 24 weeks of olmesartan treatment, CBF of whole brain and regional CBF of the frontal, parietal, and temporal lobe were similar to those of control subjects. Our brain SPECT data indicate that olmesartan restores brain hypoperfusion in elderly and hypertensive patients without organic damage. This ARB may have a favorable potential for cerebrovascular circulation, in addition to a blood pressure-lowering effect.

Studies on the development of 99mTc-labeled biphosphonate alginate beads.

The preparation of alginate-dextran pyrophosphate/biphosphonate loaded beads, were labeled with technetium-99m ((99m)Tc) and rhenium-188 ((188)Re). The radiolabelled phosphonic acid derivatives,are well-known bone imaging agents and have also been used for bone pain palliation treatment. The alginates have been used extensively as an excipient in drug products due to their thickening, gel forming and stabilizing behavior. The aim of this study was the preparation of alginate polymeric beads with and without dextran coating, to be used for imaging and possible treatment. We studied (99m)Tc-labelled biphosphonate alginates. We reported our results on the basis of size, swelling capacity and the coating material. The size effect of loading, decreases size and increases loading capacity of alginate beads. Pyrophosphate (PYP) loaded beads had 95% swelling, while ethylene diamine tetramethylene phosphonic acid (EDTMP) loaded beads had 90% (swelling). However combination of both (PYP+EDTMP) loaded beads had 95% swelling. Sustained drug release study indicated different ratios of EDTMP, PYP and EDTMP+PYP loaded beads on different days. Total drug extracted from 30 g beads was 1365.45 µg, 5352.86 µg and 711.8 µg, from EDTMP, PYP and EDTMP+PYP respectively during 15 days of studies. Binding with PYP and EDTMP was 98% and 99% respectively. In conclusion, (chemical and physical characteristics of (99m)Tc-biphosphonate and other alginate beads that we have prepared suggest that the alginate beads could be used for diagnostic and therapeutic purposes.).

Bifunctional bisphosphonate complexes for the diagnosis and therapy of bone metastases.

Easily synthesised and structurally well-defined novel imaging/therapeutic radiopharmaceutical agents for bone metastases are described.

The use of technetium-99m radiolabeled human antimicrobial peptides for infection specific imaging.

Bacterial resistance to conventional antibiotics poses a challenge medicine to search for alternatives. Cationic antimicrobial peptides (AMPs) are promising for the development of a new class of antibiotics. This review focuses on the use of technetium-99m labeled synthetic AMPs, derived from human natural cationic AMPs, for target-delivery to and in vivo detection of infection sites caused by (drug-resistant) micro-organisms. The scintigraphic approach has proven to be a reliable method for evaluating AMPs in pharmacological studies and for optimizing target-delivery of radiolabeled AMPs to pathological sites in animals and humans. In addition, the effect of alterations in amphipathicity, amino acid substitution, and dimerization on the biological performance of AMPs is reported. Radiolabeled AMPs offer good perspectives for diagnosis of infections, for monitoring therapy, and, most importantly, for the ability to discriminate between infections and sterile inflammatory processes.