From Bench to Bedside—The Bad Berka Experience With First-in-Human Studies

Precision oncology is being driven by rapid advances in novel diagnostics and therapeutic interventions, with treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations. Inherent in the theranostics paradigm is the assumption that diagnostic test results can precisely determine whether an individual is likely to benefit from a specific treatment. As part and integral in the current era of precision oncology, theranostics in the context of nuclear medicine aims to identify the appropriate molecular targets in neoplasms (diagnost…

Processing of Generator-Produced 68Ga for Medical Application

The (68)Ge/(68)Ga generator provides an excellent source of positron-emitting (68)Ga. However, newly available "ionic" (68)Ge/(68)Ga radionuclide generators are not necessarily optimized for the synthesis of (68)Ga-labeled radiopharmaceuticals. The eluates have rather large volumes, a high concentration of H(+) (pH of 1), a breakthrough of (68)Ge, increasing with time or frequency of use, and impurities such as stable Zn(II) generated by the decay of (68)Ga, Ti(IV) as a constituent of the column material, and Fe(III) as a general impurity.We have developed an efficient route for the processing of generator-derived (68)Ga eluates, including the labeling and purification of biomolecules. Prec…

Generator-Based Radiopharmaceuticals for PET Dosimetry Before, During, and After Endoradiotherapy

Generator-derived radionuclides for PET/CT imaging are promising for optimizing targeted radiotherapy by an individual patient-based approach, applying pre-therapeutic evaluation, dosimetric calculations, and for measuring treatment response after radionuclide therapy. To realize this vision, sophisticated nuclear chemistry and radiopharmaceutical chemistry should coincide with quantitative molecular imaging and dosimetric calculations.

Novel Monoclonal Antibody 138H11 Against Human γ-Glutamyl-Transferase: Classification, Histogenesis and Immunoscintigraphy of Renal Tumors

Monoclonal antibody (mAb) 138H11 was produced against human gamma-glutamyl transferase as a molecular probe for renal cancer. Immunohistochemical analyses of mAb 138H11 revealed its reaction with the brush border of normal kidney cortex as well as with clear cell and chromophilic renal carcinomas. In contrast, renal oncocytomas, chromophobic carcinomas, and Duct-Bellini carcinomas were negative for this antibody. These results support a new approach for the histogenesis and classification of renal tumors. Immunoscintigraphy of tumor bearing human kidneys, perfused with 99Tcm-labeled mAb 138H11 after nephrectomy, showed enrichment of 138H11 in three of three clear cell carcinomas that was up…

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases.

Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are ofte…

1st World Congress on Ga-68 and Peptide Receptor Radionuclide Therapy (PRRNT), June 23-26, 2011, Zentralklinik Bad Berka, Germany

Instant kit preparation of 68Ga-radiopharmaceuticals via the hybrid chelator DATA: clinical translation of [68Ga]Ga-DATA-TOC

Purpose The widespread use of 68Ga for positron emission tomography (PET) relies on the development of radiopharmaceutical precursors that can be radiolabelled and dispensed in a simple, quick, and convenient manner. The DATA (6-amino-1,4-diazapine-triacetate) scaffold represents a novel hybrid chelator architecture possessing both cyclic and acyclic character that may allow for facile access to 68Ga-labelled tracers in the clinic. We report the first bifunctional DATA chelator conjugated to [Tyr3]octreotide (TOC), a somatostatin subtype 2 receptor (SST2)-targeting vector for imaging and functional characterisation of SSTR2 expressing tumours. Methods The radiopharmaceutical precursor, DATA…

Generator-based PET radiopharmaceuticals for molecular imaging of tumours: on the way to THERANOSTICS.

Generator-derived radionuclides for PET/CT imaging are promising for optimizing targeted radiotherapy by an individual patient-based approach, applying pre-therapeutic evaluation, as well as dosimetric calculations, and for measuring treatment response after radionuclide therapy.

Development of a [177Lu]BPAMD Labeling Kit and an Automated Synthesis Module for Routine Bone Targeted Endoradiotherapy

Painful bone lesions, both benign and metastatic, are often managed using conventional analgesics. However, the treatment response is not immediate and is often associated with side-effects. Radionuclide therapy is used for pain palliation in bone metastases as well as some benign neoplasms. Endoradiotherapy has direct impact on the pain-producing bone elements, and hence, response is significant, with minimal or no side-effects. A new potential compound for endoradiotherapy is [(177)Lu]BPAMD. It combines a highly affine bisphosphonate, covalently bridged with DOTA through an amide bond, with the low-energy β(-) emitting therapeutic radiolanthanide (177)Lu. For routine chemical application,…

68Ga- und 177Lu-markierte Bisphosphonate als Knochenmetastasen-Theranostika

Der erhohte Metabolismus der Knochenmatrix kann zum einen mit der SPECT- und zum anderen mit der PET-Technik visualisiert werden. Als SPECT-Nuklid wird uberwiegend 99 mTc in Form von [99mTc]Bisphosphonat-Komplexen verwendet. Die PET bietet im Gegensatz zur SPECT eine hohere lokale und temporale Auflosung. Mit dem 68Ge/68Ga-Generatorsystem existiert ein mittlerweile bewahrtes PET-Pendant zum etablierten 99mTc-Generator. Neuartige Bisphosphonate (BP) in Kombination mit makrozyklischen Chelatoren sind derzeit weltweit Gegenstand der Forschung. Zur Komplexierung von Ga(III) werden haufig DOTA und NOTA sowie deren Derivate verwendet. Speziell im Fall von DOTA-Derivaten bieten DOTA-BP die Moglich…