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BACKGROUND: Peptide receptor radionuclide therapy (PRRT) for metastatic or inoperable neuroendocrine tumours (NETs) is a systemic therapy which targets somatostatin receptors overexpressed by differentiated NETs for endoradiotherapy. This guideline has been compiled by the College of Nuclear Physicians of the Colleges of Medicine of South Africa, with endorsement by the South African Society of Nuclear Medicine and the Association of Nuclear Physicians to guide Nuclear Medicine Physicians in its application during the management of these patients. RECOMMENDATIONS: Patients with well- to moderately-differentiated NETs should be comprehensively worked-up to determine their suitability for PRRT. Treatment should be administered by a Nuclear Medicine Physician in a licensed, appropriately equipped and fully staffed facility. Patient monitoring is mandatory during and after each therapy cycle to identify and treat therapy-related adverse events. Patients should also be followed-up after completion of therapy cycles for monitoring of long-term toxicities and response assessment. CONCLUSION: PRRT is a safe and effective therapy option in patients with differentiated NETs. Its use in appropriate patients is associated with a survival benefit.

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 often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter 177Lu. This overview describes the possibility of diagnosing bone metastases using [68Ga]Ga-BPAMD (68Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [177Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new 68Ga- and 177Lu-labeled bisphosphonates offering improved pharmacological properties.

In breast cancer CA 15.3 is considered the tumour marker of choice. CA 15.3 is directly related to the disease extent and to hormone status (estrogen receptor ER+/ ER-, progesterone receptor PR+/PR-). This study was designed to assess the impact of disease extent, hormone receptor and HER2-status, and circulating blood volume on the area-under the ROC-curve of CA 15.3 to separate FDG PET positive from negative findings. Patients, methods: We retrospectively evaluated 379 FDG PET/CT examinations performed in 80 patients with breast cancer. Blood volumes were derived using the formulas by Nadler and multiplied by their corresponding CA 15.3 measurement. Results: ROC-curve analysis revealed an AUC of 0.695 (p = 0.0001) for CA 15.3 to separate FDG PET positive from negative findings. AUC measurements to separate normal scan findings from loco-regional disease and metastatic disease were 0.527 (p = 0.587) and 0.732 (p = 0.0001), respectively. AUC measurements for CA 15.3 to separate positive from negative FDG PET findings, in ER+ and ER-patients, were respectively 0.772 (p = 0.0001) and 0.596 (p = 0.143). AUC measurements for CA 15.3 to separate positive from negative FDG PET findings, in PR+ and PR-patients, were respectively 0.675 (p = 0.0001) and 0.694 (p = 0.0001). In HER2-positive and -negative patients, the AUC measurements were respectively 0.594 (p = 0.178) and 0.701 (p = 0.0001) to separate positive from negative FDG PET findings. Conclusion: The AUC for CA 15.3 measurements to separate FDG PET positive from negative findings in breast cancer patients with suspected recurrence proved to be directly related to the extent of the recurrent disease and hormone receptor status and inversely related to HER2-status. Correcting CA 15.3 measurements for blood volumes did not impact the AUC.

195mPt-cisplatin is regarded as a promising imaging agent for optimizing dosage in patients receiving cisplatin chemotherapy. We investigated the whole-body distribution and radiation dosimetry of 195mPt-cisplatin in humans. Methods: Whole-body scans were obtained up to 144 h after intravenous injection of 112.4 MBq 195mPt-cisplatin in each of five subjects. Blood samples were taken at various times up to 144 h after injection. Urine was collected up to 114 h after injection for calculation of renal clearance and wholebody clearance. Time/activity curves were generated by fitting the organ-specific geometric mean counts, obtained from regions of interest, on the respective images as a function of the time after injection. OLINDA software package was applied to calculate the absorbed radiation dose for various organs. Results: Most of the activity (32 ± 4%) was excreted in the urine during the first 5 h. The effective clearance half-life derived from extrapolation of the whole-body curve was 40 hours (1.7 days). On average, the highest dose was received by the kidneys (mean dose received 2.68 ± 1.5 mGy/MBq), followed by the spleen (mean dose received 1.6 ± 0.8 mGy/MBq) followed by the liver (mean dose received 1.45 ± 0.38 mGy/MBq). The estimated mean effective dose for the adult subject was 0.185 ± 0.034 mSv/MBq. Conclusion: 195mPt-cisplatin proved a safe radiopharmaceutical with a favourable biodistribution for early and delayed imaging of pathology above the diaphragm. The ED obtained was 0.185 ± 0.034 mSv/MBq. The highest organ dose was received by the kidneys (2.68 ± 1.5 mGy/MBq). http://nuk.schattauer.de/de/inhalt/archivestandard.html

A 27-year-old neurologically disabled but fully conscious male zolpidem-responder patient was investigated for blood-brain barrier (BBB) dysfunction 5 years after a traumatic brain injury. A baseline single-photon emission computed tomography (SPECT) technetium-99m-labelled hexamethylpropylene amine oxime (99mTcHMPAO) brain scan was performed and the patient was administered 10 mg zolpidem daily. The patient was rescanned 2 weeks later when 99mTcHMPAO was injected 1 hour after zolpidem application. SPECT technetium-99m-labelled diethylene-triamine-pentacetic acid (99mTcDTPA) BBB scans were also performed before and after zolpidem treatment. There was decreased uptake of 99mTcHMPAO in the left frontoparietal brain region, left temporal region and left thalamus on baseline scanning; this improved within 1 hour after Zolpidem treatment at the follow-up scan. The 99mTcDTPA scan remained within normal limits before and after Zolpidem treatment. The patient's neurological disabilities, especially coordination, speech and gait, improved markedly. The Barthel index remained normal, but the Tinetti falls efficacy scale improved from 21/100 to 15/100. The results implied that the underlying cause for the patient's long-term neurological disability and brain suppression was not due to a long-term dysfunctional BBB.

Pheochromocytomas are catecholamine-producing neuroendocrine tumours that arise from the adrenal medulla or extramedullary pheochromoblasts with highly variable clinical presentation, including episodes of headache, sweating, palpitations and hypertension. Due to the non-specificity of the symptoms there is usually a delay between the onset of symptoms and the final diagnosis. To make a firm diagnosis, biochemical testing of the blood (catecholamines) or urine (metanephrines and VMA) are mandatory. Many stimuli increase circulating catecholamines and metabolites and must receive due attention to prevent false-positive results. Therapeutically, surgery is the gold standard. To minimise complications during and post surgery the lesion(s) should be carefully localised via imaging studies. Adequate pre- and postoperative medical treatment is important. The history, diagnosis and therapy of two patients - the one with a paraganglioma of the organ of Zuckerkandl, the other with a intra thoracic paraganglioma are presented. South African Family Practice Vol. 49 (5) 2007: pp. 42-45

Purpose Postoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41. Methods Patients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%). Results Significant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64–0.92) and 0.80 (95% CI: 0.64–0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal to 0.938 (95% CI: 0.80–1.00). Conclusion [18F]FDG PET/CT and MRI both possess equally satisfactory diagnostic performance in patients with suspected postoperative spine infection, the best diagnostic performance being obtained by combining MRI with [18F]FDG PET/CT. The diagnostic performance of SPECT/CT with 99mTc-UBI 29-41 was suboptimal in the postoperative clinical setting explored with the present study.

PhD (Pharmaceutics), North-West University, Potchefstroom Campus The Pheroid® drug delivery system can change the route of administration from the parenteral route to the oral route. This system is therefore investigated as a safe alternative formulation that can also contribute to better patient compliance. Pheroid® technology is currently on the verge of being applied in the clinical environment and an in-depth evaluation of this system’s toxicity is provided as an original research article (submitted to Toxicology Reports). This is a prerequisite for any registration as a new pharmaceutical entity. The oral formulation of 99mTechnetium methyl diphosphonate demonstrated potential in previous evaluations in Sprague Dawley rats as an alternative to intravenous injections of this radiopharmaceutical. This radiopharmaceutical was selected for evaluation based on clinical need (providing bone scans to patients contra-indicated for injections) as well as the high availability of 99mTc as radiotracer. A clinical trial was designed as a hybrid Phase I/II clinical trial with 16 volunteers. The trial was performed according to Good Clinical Practise regulations, and three patients were enrolled before the study was terminated due to lack of efficacy. Valuable information regarding the Pheroid® delivery system was gained and this application of Pheroid® will be refined and pursued further in the future. A review article is provided (submitted to the Journal of Controlled Release) regarding the application of drug delivery systems in nuclear medicine. This article provides insight into the shortcomings of nuclear medicine that can be addressed by the utilization of drug carrier systems such as Pheroid®. A preclinical evaluation of the pharmacokinetics (for a 5 hour period) as well as a basic toxicology analysis, of oral insulin (entrapped in Pheroid®) was performed on Cynomolgus monkeys. Insulin was formulated in pro-Pheroid® capsules as well as a Pheroid® emulsion and administered through the oral route. The efficacy was evaluated based on a drop in blood glucose levels. A blood clinical biochemistry analysis was also performed to gain information regarding the physiological impact of this system (with the entrapped insulin). The pro-Pheroid® formulations lacked efficacy, but the Pheroid® emulsion was effective and demonstrated a longer-acting effect when compared to the short acting subcutaneous control insulin. The positive results gained in this study indicate that further investigations should be launched. This thesis successfully demonstrated the safety of the Pheroid® delivery system for future applications, provided a summary regarding the nuclear application thereof and showed potential in second non-rodent model for the insulin Pheroid® formulation. Die Pheroid® geneesmiddelafleweringssisteem kan die roete van toediening van die parenterale roete tot orale roete verander. Hierdie sisteem word ondersoek as ʼn veilige alternatiewe formulering wat ook kan bydrae tot beter pasiënte aanvaarding van terapie. Pheroid® tegnologie is op die punt van implementering in die kliniese omgewing en ʼn in diepte evaluering van die sisteem se toksisiteit word verskaf as oorspronklike navorsingings artikel (ingestuur vir publikasie aan Toxicology Reports). Die toets van toksisiteit is ʼn voorvereiste vir enige registrasie as ʼn nuwe farmaseutiese entiteit. Die orale formulering van 99mTechnetium metieldifosfonaat in Pheroid® het voorheen in pre-kliniese toetse in Sprague Dawley rotte om ʼn effektiewe alternatief te wees vir intraveneuse inspuitings van hierdie radioaktiewemerker. Hierdie merker was gekies vir evaluasie op grond van kliniese aspekte (verskaf been skanderings aan pasiënte gekontradikteer vir intraveneuse toedienings bv. pediatriese pasiënte) asook die hoë beskikbaarheid van hierdie isotope (99mTc) in Suid-Afrika. Die kliniese proef was ontwerp as ʼn hibried fase I/II kliniese proef met 16 pasiënte wat gewerf moes word. Good Clinical Practise standaarde was gevolg en drie pasiënte het deelgeneem aan die proef tot die voortydige staking as gevolg van ʼn tekort aan effektiwiteit. Waardevolle inligting was gedurende hierdie evaluasie bekom en hierdie toepassing van Pheroid® sal verfyn en verder nagevolg word in die toekoms. ʼn Opsommende artikel (ingedien aan die Journal of Controlled Release) oor die toepassing van geneesmiddel afleweringssisteme in kerngeneeskunde word ook verskaf. Hierdie artikel beskryf die tekortkominge van kerngeneeskunde wat deur die toepassing van geneesmiddel draers soos Pheroid® opgelos kan word. ʼn Prekliniese evaluering van orale insulien (vasgevang in Pheroid®) was uitgevoer op Cynomolgus primate vir ʼn tydperk van 5 ure, asook ʼn basiese toksikologie analise. Hierdie hoofstuk word ook voorgedra as ʼn oorspronklike navorsingsartikel. Insulien was geformuleer in pro-Pheroid® kapsules asook ʼn Pheroid® emulsie en was toegedien deur die orale roete. Die effektiwiteit was gevalueer deur na die verlaging in bloedglukosevlakke te kyk. ʼn Evaluasie van die bloed se kliniese biochemie eienskappe was gedoen om verdere inligting te verskaf aangaande die fisiologiese effek van hierdie formulering (met die inuslien geïnkorporeer in Pheroid®. Die pro-Pheroid® formulering het nie effektiwiteit getoon nie, maar die Pheroid® emulsie was effektief en het ʼn langwerkende effek getoon in vergelyking met die kortwerkende subkutaneuse kontrole insulien. Die postiewe resultate wat in hierdie studie verkry is dui aan dat verdere ondersoeke onderneem moet word. Hierdie tesis het die veiligheid van Pheroid® bewys vir toekomstige toepassings daarvan, het ekstra inligting verskaf aangaande die kerngeneeskunde toepassing van Pheroid® asook potensiaal demonstreer in ʼn tweede nie-knaagdier model van die insulien Pheroid® formulering. National Research Foundation (NRF). Nuclear Technologies in Medicine and Biosciences Initiative (NTemBI) Doctoral