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This study explores the possibility of formulation of a cold kit for fast and easy preparation of a PET radiopharmaceutical, 68Ga-NOTA-UBI (29-41) for clinical translation. In this study, Circular dichroism (CD) spectroscopy to study conformation of NOTA-UBI (29-41) and its comparison with conformation of UBI (29-41) was done. Pharmaceutical grade cold kits of NOTA-UBI (29-41) were formulated for radiolabeling with 68Ga and necessary quality control tests were carried out. 68Ga-NOTA-UBI (29-41) could be prepared in >90% radiochemical yield and radiochemical purity using cold kits of NOTA-UBI (29-41). In vitro and in vivo evaluation of 68Ga-NOTA-UBI (29-41) was done to demonstrate specificity of the agent for imaging infection. Kits were utilized for preparation of patient dose of 68Ga-NOTA-UBI (29-41). Simple instant thin layer chromatography (ITLC) method for estimating radiolabeling yield of 68Ga-NOTA-UBI (29-41) at hospital radiopharmacy was demonstrated. Clinical evaluation was done in patients with suspected infection. 148-185 MBq of 68Ga-NOTA-UBI (29-41) was injected intravenously in three patients. 68Ga-NOTA-UBI (29-41) uptake could clearly delineate infection foci from non target normal tissues. This is the first report on formulation of a cold kit of NOTA-UBI (29-41) for preparation of 68Ga labeled NOTA-UBI(29-41) at hospital radiopharmacy for infection imaging. Initial clinical evaluation reveal it to be a prospective agent for imaging infection.

Introduction Gallium-68 based infection imaging agents are in demand to detect infection foci with high spatial resolution and sensitivity. In this study, Ubiquicidin derived octapeptide, UBI (31–38) conjugated with macrocyclic chelator NOTA was radiolabeled with 68Ga to develop infection imaging agent. Methods Circular dichroism (CD) spectroscopy was performed to study conformational changes in UBI (31–38) and its NOTA conjugate in a “membrane like environment”. Radiolabeling of NOTA-UBI (31–38) with 68Ga was optimized and quality control analysis was done by chromatography techniques. In vitro evaluation of 68Ga-NOTA-UBI (31–38) in S. aureus and preliminary biological evaluation in animal model of infection was studied. Initial clinical evaluation in three patients with suspected infection was carried out. Results 68Ga-NOTA-UBI (31–38) was prepared in high radiochemical yields and high radiochemical purity. In vitro evaluation of 68Ga-NOTA-UBI (31–38) complex in S. aureus confirmed specificity of the agent for bacteria. Biodistribution studies with 68Ga-NOTA-UBI (31–38) revealed specific uptake of the complex in infected muscle compared to inflamed muscle with T/NT ratio of 3.24 ± 0.7 at 1 h post-injection. Initial clinical evaluation in two patients with histopathologically confirmed infective foci conducted after intravenous injection of 130–185 MBq of 68Ga-NOTA-UBI (31–38) and imaging at 45–60 min post-injection revealed specific uptake at the sites of infection and clearance from vital organs. No uptake of tracer was observed in suspected infection foci in one patient, which was proven to be aseptic and served as negative control. Conclusion This is the first report on 68Ga labeled NOTA-UBI (31–38) fragment for prospective infection imaging.

The aim of this study was to formulate an indigenous cold kit of Ubiquicidin, UBI (29-41), for easy preparation of (99m)Tc-UBI (29-41) to be used as an infection imaging agent. A two component kit with the peptide and SnCl2 as vial 1 and optimum amount of NaOH as vial 2 was successfully formulated as seen from the consistent radiochemical and pharmaceutical purity of the product over six consecutive batches of kits. The utility of the kit could be demonstrated through in-vitro and in vivo specificity of (99m)Tc-UBI (29-41).

Radionuclide procedures frequently are performed as part of the diagnostic workup of osteomyelitis. Bone scintigraphy accurately diagnoses osteomyelitis in bones not affected by underlying conditions. Degenerative joint disease, fracture, and orthopedic hardware decrease the specificity of the bone scan, making it less useful in these situations. Gallium-67 scintigraphy was often used as an adjunct to bone scintigraphy for diagnosing osteomyelitis. However, now it is used primarily for spinal infections when (18)F-FDG imaging cannot be performed. Except for the spine, in vitro-labeled leukocyte imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. Leukocytes accumulate in bone marrow as well as in infection. Performing complementary bone marrow imaging with (99m)Tc-sulfur colloid facilitates the differentiation between osteomyelitis and normal marrow and improves test overall accuracy. Antigranulocyte antibodies and antibody fragments, such as (99m)Tc-besilesomab and (99m)Tc-sulesomab, were developed to eliminate the disadvantages associated with in vitro-labeled leukocytes. These agents, however, have their own shortcomings and are not widely available. As biotin is used as a growth factor by certain bacteria, (111)In-biotin is useful to diagnose spinal infections. Radiolabeled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, can differentiate infection from sterile inflammation and may be useful to monitor response to treatment. (18)F-FDG is extremely useful in the diagnostic workup of osteomyelitis. Sensitivity in excess of 95% and specificity ranging from 75%-99% have been reported. (18)F-FDG is the radionuclide test of choice for spinal infection. The test is sensitive, with a high negative predictive value, and reliably differentiates degenerative from infectious vertebral body end-plate abnormalities. Data on the accuracy of (18)F-FDG for diagnosing diabetic pedal osteomyelitis are contradictory, and its role for this indication remains to be determined. Initial investigations suggested that (18)F-FDG accurately diagnoses prosthetic joint infection; more recent data indicate that it cannot differentiate infection from other causes of prosthetic failure. Preliminary data on the PET agents gallium-68 and iodine-124 fialuridine indicate that these agents may have a role in diagnosing osteomyelitis.

Background Previous studies demonstrated that 99m Tc-labeled-ubiquicidin 29–41 ( 99m Tc-UBI 29–41) imaging is an accurate method for detection of bacterial infections. This study was conducted to evaluate the clinical use of 99m Tc-UBI 29–41 for detection of mediastinitis after cardiac surgery. Methods Thirteen patients with suspected mediastinitis after cardiac surgery were included. Qualitative and semiquantitative analyses of 99m Tc-UBI 29–41 images were performed. Mediastinitis was confirmed by bacterial culture. Results Qualitative analysis correctly identified the infection in 5/6 patients with mediastinitis. For observer 1, there were five true-positive results, six true-negative results, one false-positive result and one false-negative result (sensitivity: 83%, specificity: 85%, positive predictive value: 83%, negative predictive value: 85%, and overall diagnostic accuracy: 84%). For observer 2, there were five true-positive results, five true-negative results, two false-positive results and one false-negative result (sensitivity: 83%, specificity: 71%, positive predictive value: 71%, negative predictive value: 83%, and overall diagnostic accuracy: 76%). Agreement between observers was 0.847 (SE=0.145, p =0.002). Semiquantitative analysis showed a higher mediastinum uptake of the 99m Tc-UBI 29–41 in patients with mediastinitis than that derived from patients without mediastinitis. Mean uptake of 99m Tc-UBI 29–41 was 60.4±10.3 counts/pixel and 47.4±5.5 counts/pixel, respectively ( p =0.01). At the threshold value of ≥57 counts/pixel using ROC analysis, the sensitivity, specificity, positive predictive value, negative predictive value and overall diagnostic accuracy for detecting patients with mediastinitis were 83, 100, 100, 87, and 92%, respectively ( p =0.02; 95% CI: 0.65–1.10%). Conclusions 99m Tc-UBI 29–41 imaging yielded fast and promising first results for patients with suspected mediastinitis after cardiac surgery and, as such, deserves further investigation.