(153)Sm-EDTMP for pain relief of bone metastases from prostate and breast cancer and other malignancies.

Background And Aims: Approximately 85% of patients with cancer suffer severe metastatic bone pain for which radionuclide therapy has been employed for pain palliation. We undertook this study to evaluate the pain relief effect of (153)Sm-EDTMP in Mexican patients with severe and painful bone metastases from mainly prostate, breast, and renal cancer and other malignancies.

Methods: Patients (277) with intense sustained pain caused by bone metastases were referred to the Nuclear Medicine Department of the Oncology Hospital of the Mexican Social Security Institute.

¹⁵³Sm-HM for arthritic knee pain. Estimated dosimetry.

Osteoarthritis is the most common type of arthropathy and after cardiovascular diseases is the most disabling disease in developing countries. The dosimetry for the clinical application of 153-samarium-hydroxymacroaggregates (¹⁵³Sm-HM) for radiation synovectomy (RSV) and palliative treatment for arthritic pain, as far as we know, has not been reported. The aim of this research was to estimate the radiation dose necessary for synovial ablation and pain palliation with minimum risk to the patient.

Specificity and sensitivity of ⁹⁹mTc-EDDA/HYNIC-Tyr³-octreotide (⁹⁹mTc-TOC) for imaging neuroendocrine tumors.

Objectives: Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the ⁹⁹mTc-EDDA-HYNIC-Tyr³octreotide (⁹⁹mTc-TOC) to image and localize NETs and their metastases.

99mTc-N2S2-Tat (49-57)-bombesin internalized in nuclei of prostate and breast cancer cells: kinetics, dosimetry and effect on cellular proliferation.

Background: The gastrin-releasing peptide receptor (GRP-r) is overexpressed in prostate and breast cancers. technetium-99m-bombesin (Tc-BN) has been reported as a radiopharmaceutical with specific cell GRP-r binding. The HIV Tat (49-57)-derived peptide has been used to deliver a large variety of molecules to cell nuclei.

(99m)Tc-labelled gold nanoparticles capped with HYNIC-peptide/mannose for sentinel lymph node detection.

Unlabelled: The aim of this research was to prepare a multifunctional system of technetium-99m-labelled gold nanoparticles conjugated to HYNIC-GGC/mannose and to evaluate its biological behaviour as a potential radiopharmaceutical for sentinel lymph node detection (SLND).

Methods: Hydrazinonicotinamide-Gly-Gly-Cys-NH(2) (HYNIC-GGC) peptide and a thiol-triazole-mannose derivative were synthesized, characterized and conjugated to gold nanoparticles (AuNP, 20 nm) to prepare a multifunctional system of HYNIC-GGC-AuNP-mannose by means of spontaneous reaction of the thiol (Cys) present in HYNIC-GGC sequence and in the thiol-mannose derivative. The nanoconjugate was characterized by transmission electron microscopy (TEM), IR, UV-Vis, Raman, fluorescence and X-ray photoelectron spectroscopy (XPS).

Specificity of 99mTc-UBI for detecting infection foci in patients with fever in study.

Unlabelled: Fever of unknown origin (FUO) represents a challenge to clinical medicine, and bacterial cultures have been considered the 'gold standard' in discriminating between fevers resulting from bacterial infection and sterile inflammations. In nuclear medicine, a synthetic radiolabeled antimicrobial peptide (Tc-UBI) is used to image the molecular localization of infectious microorganisms.

Objective: The aim of this research was to determine the absolute and relative frequencies of Tc-UBI, by molecular imaging, to detect infection foci in patients with fever in study or FUO.

Therapeutic 188Re-lanreotide: determination of radiopharmacokinetic parameters in rats.

Objectives: The radiopharmacokinetic parameters of the therapeutic radiopharmaceutical (188)Re-lanreotide were compared in rats implanted with hepatocarcinoma tumours (n= 18) and healthy rats (n= 18).

Methods: Rats were injected with approximately 1.8 MBq (188)Re-lanreotide (0.

Clinical trial of specific imaging of infections.

Objective: For several decades Ga citrate, technetium-99m ((99m)Tc) or (111)In-labelled leukocytes have been used for imaging the inflammatory process. Unfortunately, these radiopharmaceuticals are not infection-specific markers. In preclinical settings, radiolabelled antimicrobial peptides (AMPs), such as UBI 29-41 seem to be highly infection-specific and even high doses of these peptides have shown neither toxicity nor side effects in animals.

Design, preparation, in vitro and in vivo evaluation of (99m)Tc-N2S2-Tat(49-57)-bombesin: a target-specific hybrid radiopharmaceutical.

The gastrin-releasing peptide receptor (GRP-r) is over-expressed in various human tumors. Recently, (99m)Tc-EDDA/HYNIC-Lys(3)-bombesin ((99m)Tc-BN) was reported as a radiopharmaceutical with specific cell GRP-r binding and images in breast cancer patients demonstrated distinct radioactivity accumulation in malignant tissue. The HIV Tat-derived peptide has been used to deliver a large variety of cargoes into cells.

Targeted imaging of gastrin-releasing peptide receptors with 99mTc-EDDA/HYNIC-[Lys3]-bombesin: biokinetics and dosimetry in women.

Background: The gastrin-releasing peptide receptor (GRP-R) is expressed in several normal human tissues and is overexpressed in various human tumors including breast, prostate, small-cell lung cancer and pancreatic cancer. Recently, 99mTc-EDDA/HYNIC-[Lys]-bombesin (99mTc-HYNIC-BN) was reported as a radiopharmaceutical with high stability in human serum, specific cell GRP-R binding and rapid cell internalization.

Aim: The aim of this study was to determine the biokinetics and dosimetry of 99mTc-HYNIC-BN and the feasibility of using this radiopharmaceutical to image GRP-R in four early breast cancer patients and seven healthy women.

Pharmacokinetics and dosimetry of 188 Re-pharmaceuticals.

The main objective of this review is to apportion current and new insight into the biodistribution, radiopharmacokinetics, dosimetry and cell targeting of rhenium-188 labeled radiopharmaceuticals used as therapeutic drugs. The emphasis lies on the generator obtained rhenium-188, its physical, therapeutic, dosimetric and coordinated compounds. Its use in radioimmunotherapy for lymphoma and other hematological diseases with monoclonal antibodies is discussed.

[Current developments in SPECT/CT systems using 99mTc-radiopharmaceuticals].

The 3 foundations of nuclear medicine are radiation conscious personnel, specific radiopharmaceuticals and equipment. The trend in molecular radiopharmacy is to develop new radiopharmaceuticals targeting peptides and receptors. 99mTc-radiopharmaceuticals give important clinical and molecular information especially in endocrinology, oncology and cardiology.

Biokinetics and dosimetry of 188Re-anti-CD20 in patients with non-Hodgkin's lymphoma: preliminary experience.

Background: Radioimmunotherapy is a molecular targeting treatment for high-risk leukemia and lymphoma. Rhenium-188-labeled anti-CD66 monoclonal antibody has been used successfully in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome. Our aim was to establish the biokinetics of (188)Re-anti-CD20 in patients and to evaluate its dosimetry as a target-specific radiopharmaceutical for non-Hodgkin's lymphoma (NHL) radioimmunotherapy.

Synthesis of oxytocin HYNIC derivatives as potential diagnostic agents for breast cancer.

Two synthetic procedures for HYNIC oxytocin labeling were developed: one based on an orthogonal protection approach and the other with prelabeled (Boc)HYNIC-(Fmoc) amino acids. Both procedures were compared and applied to the preparation of several HYNIC-oxytocin derivatives where ligand position and amino acid (lysine and phenylalanine) were varied. Additionally, an oxytocin derivative labeled with HYNIC in the alpha-amino group of the Cys1 residue was also prepared.

Biokinetics and dosimetry in patients of 99mTc-EDDA/HYNIC-Tyr3-octreotide prepared from lyophilized kits.

99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. The aim of this study was to establish a biokinetic model for 99mTc-HYNIC-TOC prepared from lyophilized kits, and to evaluate its dosimetry as a tumor imaging agent in patients with histologically confirmed neuroendocrine tumors. Whole-body images from eight patients were acquired at 5, 60, 90, 180 min and 24 h after 99mTc-HYNIC-TOC administration obtained from instant freeze-dried kit formulations with radiochemical purities >95%.

Preparation and evaluation of 99mTc-EDDA/HYNIC-[Lys 3]-bombesin for imaging gastrin-releasing peptide receptor-positive tumours.

Background: Bombesin is a peptide that was initially isolated from frog skin and which belongs to a large group of neuropeptides with many biological functions. The human equivalent is gastrin-releasing peptide (GRP), whose receptors are over-expressed in a variety of malignant tumours.

Aim: To prepare a HYNIC-[Lys 3]-bombesin analogue that could be easily labelled with 99mTc from lyophilized kit formulations and to evaluate its potential as an imaging agent for GRP receptor-positive tumours.

Radiopharmacokinetic and dosimetric parameters of 188Re-lanreotide in athymic mice with induced human cancer tumors.

Radiolabeled peptides, like the somatostatin analogs, have been used for peptide receptor-mediated radionuclide therapy (PRMRT) in metastatic neuroendocrine tumors. The eight amino acid peptide 3-(2-naphthalenyl)-D-alanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-cysteinyl-L-threoninamide,cyclic(2-->7)-disulfide (9Cl) (lanreotide) was found to bind to the five somatostatin tumor receptors. Lanreotide has been labeled via the bifunctional chelating agent, DOTA, to (111)In, and (90)Y.

An efficient, reproducible and fast preparation of 188Re-anti-CD20 for the treatment of non-Hodgkin's lymphoma.

Background: Therapies using Y-anti-CD20 or I-anti-CD20 have demonstrated their efficacy in patients with B-cell non-Hodgkin's lymphoma. Re is a radionuclide useful for radioimmunotherapy.

Aim: To develop a procedure for efficient labelling of anti-CD20 with Re from lyophilized formulations to achieve high radiochemical yield, high specific activity and preservation of the molecular recognition after a simple kit reconstitution without further purification.

Cytotoxic and genotoxic effect of the [166Dy]Dy/166Ho-EDTMP in vivo generator system in mice.

Multiple myeloma and other hematological malignancies have been treated by myeloablative radiotherapy/chemotherapy and subsequent stem cell transplantation. [(166)Dy]Dy/(166)Ho-ethylenediaminetetramethylene phosphonate (EDTMP) forms a stable in vivo generator system with selective skeletal uptake in mice; therefore, it could work as a potential and improved agent for marrow ablation. Induced bone marrow cytotoxicity and genotoxicity are determined by the reduction of reticulocytes (RET) and elevation of micronucleated reticulocyte (MN-RET) in peripheral blood and ablation by bone marrow histological studies.

Molecular recognition and stability of 99mTc-UBI 29-41 based on experimental and semiempirical results.

99mTc-UBI 29-41 is an antimicrobial peptide fragment that directly radiolabeled with 99mTc shows high in vitro and in vivo stability, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites. Molecular mechanics (MM) calculation has been an essential tool in explaining experimental results associated with molecular recognition and stability. This work is an attempt to explain the 99mTc-UBI 29-41 specificity for bacteria and to understand from a structural point of view, the experimental results indicative of a molecular recognition and stability not well favored for two other cationic peptides (99mTc-Tat-1-Scr and 99mTc-Tat-2-Scr ) used as control.

Preparation of (166)Dy/(166)Ho-EDTMP: a potential in vivo generator system for bone marrow ablation.

Background And Aim: Bone-seeking radiopharmaceuticals have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other haematological malignancies. The aim of this research was to examine the feasibility of labelling ethylenediaminetetramethylenephosphonate (EDTMP) with Dy/Ho as an in vivo generator system and to evaluate whether the in vitro and in vivo stability of Dy-EDTMP and Ho-EDTMP complexes is maintained when the daughter Ho is formed.

Methods: Dy was obtained by neutron irradiation of enriched Dy2O3 in a TRIGA Mark III reactor.

Biokinetics of (99m)Tc-UBI 29-41 in humans.

Antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. (99m)Tc-UBI labeled by a direct method has shown high in vitro and in vivo stability, specific uptake at the site of infection, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites in mice. The aim of this study was to establish a (99m)Tc-UBI biokinetic model and evaluate its feasibility as an infection imaging agent in humans.

Lys and Arg in UBI: a specific site for a stable Tc-99m complex?

The aim of this study was to help establish if ubiquicidin peptide 29-41 fragment (UBI) contains a specific site for 99mTc labeling by a new direct method under alkaline conditions. Since this peptide does not have cysteine residues, it is possible that neighboring arginine and lysine in the peptide amino acid sequence (Thr-Gly-Arg-Ala-Lys-Arg-Arg-Met-Gln-Tyr-Asn-Arg-Arg) could be a specific coordination site to form a stable 99mTc-UBI complex. Following direct labeling, the in vitro stability of 99mTc-UBI was compared to UBI radiolabeled by one indirect method using HYNIC/tricine and HYNIC/tricine/EDDA.

In vitro and in vivo assessment of 99mTc-UBI specificity for bacteria.

Technetium-99m labeled ubiquicidin peptide 29-41 ((99m)Tc-UBI) is a cationic human antimicrobial peptide fragment that has been shown to bind bacteria in vitro and accumulates at sites of infection in experimental animals. To help determine if (99m)Tc-UBI is bound to the bacterial cell envelope by a simple nonspecific electrostatic interaction, a comparative study of the in vitro binding of (99m)Tc-UBI and two different (99m)Tc labeled cationic peptides ((99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr) to bacteria and to two tumor cell line (LS174T and ACHN) was performed. The in vivo specificity of (99m)Tc-UBI for infection in mice was also evaluated using dual labels in the same animal and comparing the target/non-target ratio for (67)Ga-citrate and (99m)Tc-UBI at sites of induced infection and sterile inflammation.