Samarium-153 chelate localization in malignant melanoma

153Sm, a radiolanthanide of half life 46.27 h, has a gamma emission of 0.103 MeV which is well suited to imaging, it is also a moderate energy beta emitter and tumour localization of various 153Sm chelates was evaluated in B16 murine melanoma to assess their endoradiotherapeutic potential. 153Sm was prepared from enriched 152Sm in the Australian Nuclear Science and Technology Organization reactor. 153Sm chelates were prepared from 153Sm-chloride and their chromatographic behaviour characterized. Tumour and organ uptake of 153Sm-chloride, 153Sm-citrate and the 153Sm chelates, DTPA, HEDTA, HIDA, BZ, PBH, PIH and NTA were measured at 1, 6, 24 and 48 h after intravenous administration to C57 black mice bearing either melanotic or amelanotic B16 melanoma of mean size 0.75 cm3. Histopathological examination of the tumours at each passaging assured comparability of the degree of melanogenesis and the absence of necrosis. 153Sm-chloride was immobile on chromatography and the rapid hepatic accumulation of both 153Sm-chloride and 153Sm-citrate was attributed to in vivo formation of a colloid. In contrast, 153Sm-DTPA, moving at the solvent front on chromatography, showed no reticuloendothelial accumulation in vivo and was rapidly excreted by the kidneys without tumour uptake. The other 153Sm chelates were of intermediate stability and all localized in both melanotic and amelanotic tumours, although to a significantly lesser degree than 67Ga-citrate. The relatively high 153Sm-HIDA activity in liver and 153Sm-NTA activity in bone impaired tumour definition, but on imaging of all the 153Sm chelates only 153Sm-DTPA failed to demonstrate the B16 melanoma and the best tumour delineation was obtained using 153Sm-HEDTA.     

Uptake of 123I-5-iodo-2-thiouracil, a possible radiopharmaceutical for noninvasive detection of ocular melanoma, in melanotic and amelanotic melanomas in hamsters

The uptake of 123I-5-iodo-2-thiouracil in melanotic and amelanotic melanoma implanted in Syrian golden hamsters was studied. A selective accumulation was found in the tumours. Uptake of 123ITU in melanotic melanomas was 4 to 5 times the uptake in amelanotic ones. For both tumours high ratios of tumours versus non-tumour were found. The high accumulation of 123ITU in both kinds of tumours and the high tumour versus non-tumour ratios suggest that 123ITU may be a promising radiopharmaceutical for the detection of ocular melanoma.     

NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours

Purpose The purpose of this study was to assess the potential and utility of ultra-high-resolution hypoxia imaging in various murine tumour models using the established hypoxia PET tracer [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO).Methods [¹⁸F]FMISO PET imaging was performed with the dedicated small-animal PET scanner NanoPET (Oxford Positron Systems) and ten different human tumour xenografts in nude mice as well as B16 melanoma tumours in syngeneic Balb/c mice. For comparison, [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) PET scans were also performed in the mice bearing human tumour xenografts.Results In 10 out of 11 experimental tumour models, [¹⁸F]FMISO PET imaging allowed clear-cut visualisation of the tumours. Inter- and intratumoural heterogeneity of tracer uptake was evident. In addition to average TMRR (tumour-to-muscle retention ratio including all voxels in a volume of interest (VOI)), the parameters TMRR_75% and TMRR₅ (tumour-to-muscle retention ratio including voxels of 75% or more of the maximum radioactivity in a VOI and the five hottest pixels, respectively) also served as measures for quantifying the heterogeneous [¹⁸F]FMISO uptake in the tumours. The variability observed in [¹⁸F]FMISO uptake was related neither to tumour size nor to the injected mass of the radiotracer. The pattern of normoxic and hypoxic regions within the human tumour xenografts, however, correlated with glucose metabolism as revealed by comparison of [¹⁸F]FDG and [¹⁸F]FMISO images.Conclusion This study demonstrates the feasibility and utility of [¹⁸F]FMISO for imaging murine tumour models using NanoPET.     

Synthesis and evaluation of novel radioiodinated nicotinamides for malignant melanoma

INTRODUCTION: A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N-2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. METHODS: [(123)I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. RESULTS: The iodonicotinamides displayed low-affinity binding for sigma(1)-sigma(2) receptors (K(i)>300 nM). In biodistribution studies in mice, N-(2-(diethylamino)ethyl)-5-[(123)I]iodonicotinamide ([(123)I]1) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h ( approximately 8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N-alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [(123)I]1, while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [(123)I]1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [(123)I]1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. CONCLUSION: These findings suggest that [(123)I]1, which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours.     

In vivo imaging of tumour angiogenesis in mice with the α<Subscript>v</Subscript>β<Subscript>3</Subscript> integrin-targeted tracer <Superscript>99m</Superscript>Tc-RAFT-RGD

Purpose The molecular imaging of tumour neoangiogenesis currently represents a major field of research for the diagnostic and treatment strategy of solid tumours. Endothelial cells from tumour neovessels overexpress the α_vβ₃ integrin, which selectively binds to Arg-Gly-Asp (RGD)-containing peptides. We evaluated the potential of the novel radiotracer ^99mTc-RAFT-RGD for the non-invasive molecular imaging of α_vβ₃ integrin expression in mice models of tumour development. Methods ^99mTc-RAFT-RGD, ^99mTc-cRGD (specific control) and ^99mTc-RAFT-RAD (non-specific control) were injected intravenously to mice bearing B16F0 or TS/A-pc tumours. In vivo whole-body tomographic imaging and post-mortem biodistribution studies were performed 60 min following tracer injection. Adjacent tumour slices were used to compare the localisation of neovessels from immunostaining and the pattern of ^99mTc-RAFT-RGD uptake from autoradiographic ex vivo imaging. Results Biodistribution studies indicated that ^99mTc-RAFT-RGD tumour uptake was significantly higher than that of ^99mTc-RAFT-RAD in B16F0 (2.4±0.5 vs 1.0±0.1%ID/g, respectively) and in TS/A-pc tumours (2.7±0.8 vs 0.7±0.1%ID/g, respectively). Immunohistochemical and autoradiographic studies indicated that ^99mTc-RAFT-RGD intratumoural uptake preferentially occurred in angiogenic areas. Tomographic imaging allowed tumour visualisation following injection of ^99mTc-RAFT-RGD and ^99mTc-cRGD with similar tumour-to-contralateral muscle (T/CM) ratios in B16F0 and in TS/A-pc tumours whereas ^99mTc-RAFT-RAD T/CM ratios did not allow tumour imaging. In accordance with the higher level of α_vβ₃ integrin expression on TS/A-pc tumours than on B16F0 tumours as determined from western blot and immunoprecipitation analyses, the ^99mTc-RAFT-RGD T/CM ratio was significantly higher in TS/A-pc than in B16F0 tumours. Conclusion ^99mTc-RAFT-RGD allowed the in vivo imaging of α_vβ₃ integrin tumour expression.     

Limited sensitivity of iodine-123-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide whole-body scintigraphy in patients with malignant melanoma: a comparison with thallium-201 imaging

The aim of this prospective study was to assess the diagnostic value of iodine-123-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide (IBZM) whole-body imaging in comparison to thallium-201 scintigraphy in patients with metastatic malignant melanoma. Ten patients with suspected or proven locoregional metastases of malignant melanoma underwent whole-body scintigraphy both with ²⁰¹Tl and ¹²³I-IBZM prior to scheduled surgery. Whole-body scans and planar scintigrams were acquired at 5 min and 30 min after injection of 100 MBq ²⁰¹Tl and at 10 min, 2 h, 4 h and 24 h after injection of 185 MBq ¹²³I-IBZM. Ten out of 12 melanoma metastases, both melanotic and amelanotic as proven histologically, were detected by ²⁰¹Tl with a sensitivity of 83%. ¹²³I-IBZM showed tracer uptake only in 3 melanotic metastases (sensitivity: 25%) with a maximum tumor-to-background ratio within 4 h, while none of the amelanotic metastases was IBZM-positive. All lesions localized by ¹²³I-IBZM showed tracer uptake of ²⁰¹Tl as well, while ²⁰¹Tl-negative lesions were also negative with IBZM. Because of the poor results of IBZM, the study was terminated after an interim evaluation of 10 patients. ¹²³I-IBZM is a tracer with only moderate sensitivity in melanotic melanoma lesions, suggesting that this method has no clinical value as a routine investigation in melanoma patients. In comparison, our previous results with ²⁰¹Tl whole-body scintigraphy yielded a significantly higher sensitivity of about 80% in patients with locoregional melanoma metastases and may thus offer considerable potential in non-PET melanoma imaging. Received 13 June 1999 and in revised form 4 August 1999     

Potential radiopharmaceuticals for the detection of ocular melanoma

In order to investigate the possibility of using [1-¹¹C] labelled 3,4-dihydroxyphenylalanine (DOPA) and tyrosine as radiopharmaceuticals for the detection of eye melanoma, the biodistributions of the same 1- and 3-¹⁴C-labelled compounds were investigated in Syrian golden hamsters with Greene melanoma. The results of these investigations were compared with positron emission tomography (PET) images of ¹¹C labelled DOPA and tyrosine. The synthesis of these ¹¹C labelled compounds procures of DL mixture, from which D and L forms can be separated. One h after intravenous injection, both ¹⁴C labelled DL-, L-and D-DOPA showed a high uptake in tumour tissue, that of DL- and D-DOPA being the highest. These high uptakes, together with relatively low uptake in bone, skin and eye resulted in high tumour/non tumour ratio (for DL-DOPA 5.9, 4.5 and 6.6 respectively). Extraction of the tumour tissue with trichloroacetic acid showed that L-DOPA was mainly incorporated into melanin, whereas D-DOPA was not. Also, the uptake 1 h after intravenous injection of 1-¹⁴C-L- and DL-tyrosine into the tumour were high, but L- and DL- were less different; tumour/non tumour ratios were favorable. PET images of the tumour obtained 40–80 min after injection of the [1-¹¹C] labelled DOPA and tyrosine confirmed that melanoma detection was promising and that D-DOPA produced a better melanoma image than L-DOPA.     

Detection of malignant melanoma with iodine-123 iodoamphetamine

Iodoamphetamine (IMP) was shown by in vitro assay to have a high uptake by human melanotic melanoma cells, as compared to amelanotic melanoma cells. Eleven patients with proven malignant melanoma (MM) and 3 normal subjects were imaged at 2-4 hr and 16-24 hr after the i.v. injection 5 mCi (185 MBq) of [123I]IMP. One patient had a recurrent tumor that was subsequently shown to be squamous cell carcinoma. The index lesion was not visualized in the three patients with amelanotic melanomas. The index lesion/lesions were visualized in six of the seven other patients, except for 4/16 nodules in one patient. The seventh patient had a large, necrotic melanotic tumor that was not visualized, but an unsuspected lesion in the iliac nodes was detected. Multiple unsuspected lesions were detected in a second patient. While many lesions were seen at 2-4 hr, all lesions (other than a patient with small bowel disease) were seen best at 16-24 hr. No eye uptake was observed in any patient or control subject. Testicular uptake was seen in all males at 16-24 hr. Iodine-123 IMP appears to be a useful agent for the detection and follow-up of patients with melanotic MM.     

Mechanism of 201Tl uptake in tumours

We have studied the mechanism of tumour uptake of ²⁰¹Tl by in vivo and in vitro studies. In a series of patients with breast cancer (n=26), lung cancer (n=56) and lymphoma (n=15), the time course of tumour uptake of ²⁰¹Tl paralleled that in the myocardium with almost identical times of peak uptake being obtained in tumours and myocardium. In a patient with hepatic metastases from colonic cancer undergoing laparotomy, ^99mTc labelled microspheres and ²⁰¹Tl were injected into the hepatic artery and biopsies of metastatic and normal liver tissue obtained. The tumour to normal liver activity ratios for ²⁰¹Tl were one tenth of those for ^99mTc microspheres. In the final part of the study, cells from a lung cancer tissue culture line were incubated for 30 min with ²⁰¹Tl with and without the addition of cardiac glycoside, which acts a sodium potassium pump blocker. The cells exposed to the cardiac glycoside showed markedly decreased uptake of ²⁰¹Tl compared to the cells not so exposed (0.6%±0.1% vs 11.8±0.7.2% of the administered dose). The mechanism of ²⁰¹Tl uptake of tumours is similar to that in the myocardium. Sodium potassium pump activity appears to be more important than tumour blood flow. ²⁰¹Tl uptake may provide a useful means of studying tumour viability.     

[<Superscript>18</Superscript>F]EF3 is not superior to [<Superscript>18</Superscript>F]FMISO for PET-based hypoxia evaluation as measured in a rat rhabdomyosarcoma tumour model

Purpose  The aim of this investigation was to quantitatively compare the novel positron emission tomography (PET) hypoxia marker 2-(2-nitroimidazol-1-yl)-N-(3[¹⁸F],3,3-trifluoropropyl)acetamide ([¹⁸F]EF3) with the reference hypoxia tracer [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO). Methods  [¹⁸F]EF3 or [¹⁸F]FMISO was injected every 2 days into two separate groups of rats bearing syngeneic rhabdomyosarcoma tumours. In vivo PET analysis was done by drawing regions of interest on the images of selected tissues. The resulting activity data were quantified by the percentage of injected radioactivity per gram tissue (%ID/g) and tumour to blood (T/B) ratio. The spatial distribution of radioactivity was defined by autoradiography on frozen tumour sections. Results  The blood clearance of [¹⁸F]EF3 was faster than that of [¹⁸F]FMISO. The clearance of both tracers was slower in tumour tissue compared with other tissues. This results in increasing T/B ratios as a function of time post tracer injection (p.i.). The maximal [¹⁸F]EF3 tumour uptake, compared to the maximum [¹⁸F]FMISO uptake, was significantly lower at 2 h p.i. but reached similar levels at 4 h p.i. The tumour uptake for both tracers was independent of the tumour volume for all investigated time points. Both tracers showed heterogeneous intra-tumoural distribution. Conclusions  [¹⁸F]EF3 tumour uptake reached similar levels at 4 h p.i. compared with tumour retention observed after injection of [¹⁸F]FMISO at 2 h p.i. Although [¹⁸F]EF3 is a promising non-invasive tracer, it is not superior over [¹⁸F]FMISO for the visualisation of tumour hypoxia. No significant differences between [¹⁸F]EF3 and [¹⁸F]FMISO were observed with regard to the intra-tumoural distribution and the extra-tumoural tissue retention.     

An evaluation of99mTc-HMPAO uptake in cerebral gliomas —a comparison with X-ray CT

Nineteen patients with biopsy-proven cerebral gliomas were studied with^99mTc-HMPAO single photon emission tomography (SPELT) imaging and X-ray computed tomography (CT). The uptake of^99mTc-HMPAO was correlated with tumour size and morphology as shown by X-ray CT, and overall patient survival. It appears that uptake of^99mTc-HMPAO is associated with larger, ill-defined tumours and was an adverse factor in patient survival. In those tumours with normal or increased uptake,^99mTc-HMPAO imaging is useful in distinguishing the tumour margin from surrounding oedema.     

Intraindividual comparison of <Superscript>68</Superscript>Ga-DOTA-TATE and <Superscript>18</Superscript>F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

Aim  To compare the diagnostic impact of ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). Methods  PET/CT using both ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Results  Patient-based sensitivities were 96% for ⁶⁸Ga-DOTA-TATE PET and 56% for ¹⁸F-DOPA PET. ⁶⁸Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by ¹⁸F-DOPA PET. Overall, ⁶⁸Ga-DOTA-TATE was superior to ¹⁸F-DOPA in 13 patients (two patients showed fewer positive tumour regions with ¹⁸F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of ¹⁸F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive ¹⁸F-DOPA uptake. In patients positive for ¹⁸F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). Conclusion  In this study ⁶⁸Ga-DOTA-TATE PET proved clearly superior to ¹⁸F-DOPA PET for detection and staging of NET. ¹⁸F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that ¹⁸F-DOPA PET should be employed in patients with NET with negative ⁶⁸Ga-DOTA-TATE PET and elevated plasma serotonin.     

Potential radiopharmaceuticals for the detection of ocular melanoma

The uptake and distribution of several 4-(substituted amino)-iodoquinolines, ¹³¹I-labelled, and of ⁶⁷Ga-citrate were investigated in Syrian golden hamsters with Greene melanomas. Because of its uptake in the melanoma (tumour/eye ratio 8.9), 4-(dimethylamino-ethylamino)-7-iodoquinoline (NM113) was selected for further investigations as a possible radiopharmaceutical for ocular scintigraphy when labelled with ¹²³I. High uptake of NM113 turned out to be incidental and could not be favourably influenced by several pharmacological pretreatments. Affinity for melanin, as shown in in vitro experiments, unfavourably influences NM113 tumour-to-eye ratios. In comparison with ⁶⁷Ga-citrate, the latter, with a high tumour-to-eye ratio (44.8 after 24 h) is more promising in patient studies in which NM113 ¹²³I was not.     

Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model

Purpose As primary osseous metastasis is the main adverse prognostic factor in patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour metastases has been established to examine the mechanisms of metastasis. The aim of this study was to evaluate the feasibility of diagnostic molecular imaging by small animal PET in this mouse model. Methods Human Ewing tumour cells were transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v. injection (n=17). The animals (mean weight 23.2 g) were studied 2–7 weeks after transplantation using a submillimetre resolution animal PET scanner. To assess glucose utilisation and bone metabolism, mice were scanned after intravenous injection of 9.6 MBq (mean) 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG) or 9.4 MBq (mean) [¹⁸F]fluoride. Whole-body PET images were analysed visually and semi-quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological uptake were identified with respect to the physiological organ uptake in corresponding regions. Results Subcutaneously transplanted Ewing tumours demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT 2.2). After i.v. transplantation, the pattern of metastasis was similar to that in patients with metastases in lung, bone and soft tissue. These metastases showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous metastases were additionally visible on [¹⁸F]fluoride PET by virtue of decreased [¹⁸F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically. Conclusion Diagnostic molecular imaging of Ewing tumours and their small metastases in an in vivo NOD/scid mouse model is feasible using a submillimetre resolution PET scanner.     

Correlation of [18F]FMISO autoradiography and pimonodazole immunohistochemistry in human head and neck carcinoma xenografts

Purpose  Tumour cell hypoxia is a common feature in solid tumours adversely affecting radiosensitivity and chemosensitivity in head and neck squamous cell carcinomas. Positron emission tomography (PET) using the tracer [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO) is most frequently used for non-invasive evaluation of hypoxia in human tumours. A series of ten human head and neck xenograft tumour lines was used to validate [¹⁸F]FMISO as hypoxia marker at the microregional level. Methods  Autoradiography after injection of [¹⁸F]FMISO was compared with immunohistochemical staining for the hypoxic cell marker pimonidazole in the same tumour sections of ten different human head and neck xenograft tumour lines. The methods were compared: first, qualitatively considering the microarchitecture; second, by obtaining a pixel-by-pixel correlation of both markers at the microregional level; third, by measuring the signal intensity of both images; and fourth, by calculating the hypoxic fractions by pimonidazole labelling. Results  The pattern of [¹⁸F]FMISO signal was dependent on the distribution of hypoxia at the microregional level. The comparison of [¹⁸F]FMISO autoradiography and pimonidazole immunohistochemistry by pixel-by-pixel analysis revealed moderate correlations. In five tumour lines, a significant correlation between the mean [¹⁸F]FMISO and pimonidazole signal intensity was found (range, r ² = 0.91 to r ² = 0.99). Comparison of the tumour lines with respect to the microregional distribution pattern of hypoxia revealed that the correlation between the mean signal intensities strongly depended on the microarchitecture. Overall, a weak but significant correlation between hypoxic fractions based on pimonidazole labeling and the mean [¹⁸F]FMISO signal intensity was observed (r ² = 0.18, p = 0.02). For the three tumour models with a ribbon-like microregional distribution pattern of hypoxia, the correlation between the hypoxic fraction and the mean [¹⁸F]FMISO signal intensity was much stronger and more significant (r ² = 0.73, p < 0.001) than for the tumours with a more homogenous, patchy, microregional distribution pattern of hypoxia. Conclusion  Different patterns of [¹⁸F]FMISO accumulation dependent on the underlying microregional distribution of hypoxia were found in ten head and neck xenograft tumours. A weak albeit significant correlation was found between the mean [¹⁸F]FMISO signal intensity and the hypoxic fraction of the tumours. In larger clinical tumours, [¹⁸F]FMISO–PET provides information on the tumour oxygenation status on a global level, facilitating dose painting in radiation treatment planning. However, caution must be taken when studying small tumour subvolumes as accumulation of the tracer depends on the presence of hypoxia and on the tumour microarchitecture. An erratum to this article can be found at     

Tumour uptake of thallium-201 chloride

The uptake of ²⁰¹Tl-chloride in tumours has recently been investigated in several authors' laboratories. We are reporting studies on the uptake in malignant melanoma in mice. Generally, we confirm the published data qualitatively in finding higher uptake in tumour than in muscle. We confirm the rapid blood clearance and high kidney concentration, but we did not measure the myocardial uptake. We observed the concentrations in kidney muscle and tumour to rise during the first four hours while that in the liver fell from one hour onwards. We did not observe markedly higher uptake in melanin rich tumour than in other tumours.     

Blood flow–metabolic relationships are dependent on tumour size in non-small cell lung cancer: a study using quantitative contrast-enhanced computer tomography and positron emission tomography

Purpose The purpose of this study was to undertake dual assessment of tumour blood flow and glucose metabolism in non-small cell lung cancer (NSCLC) using contrast-enhanced computed tomography (CE-CT) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in order to assess how the relationships between these parameters vary with tumour size and stage.Methods Tumour blood flow and glucose metabolism were assessed in 18 NSCLCs using quantitative CE-CT and FDG-PET respectively. Contrast enhancement and FDG uptake were both normalised to injected dose and patient weight to yield correspondingly the standardised perfusion value (SPV) and standardised uptake value (SUV). Tumour area was measured from conventional CT images.Results The ratio of SUV to SVP and the metabolic–flow difference (SUV–SVP) correlated with tumour size (r=0.56, p=0.015 and r=0.60 and p=0.008 respectively). A metabolic–flow difference of greater than 4 was more common amongst tumours of stages III and IV (odds ratio 10.5; 95% confidence limits 0.24–32.1). A significant correlation between SUV and SPV was found only for tumours smaller than 4.5 cm² (r=0.85, p=0.03).Conclusion Blood flow–metabolic relationships are not consistent in NSCLC but depend upon tumour size and stage. Quantitative CE-CT as an adjunct to an FDG study undertaken using integrated PET-CT offers an efficient way to augment the assessment of tumour biology with possible future application as part of clinical care.     

The mechanism of 67Ga uptake in animal and human tumours

The subcellular distribution of ⁶⁷Ga has been studied by differential centrifugation in 3 transplantable mouse tumours, 3 transplantable rat tumours, 1 dog tumour, 3 human tumour xenografts and 2 human tumours in situ at various times after injection of the citrate complex. From 24 h post injection the nuclide was located predominantly in lysosomal structures in all the tumours studied. Studies in two murine tumours showed marked differences in the rate of lysosomal accumulation of ⁶⁷Ga. In the ADJ/PC6 plasmacytoma lysosomal uptake of ⁶⁷Ga had reached a plateau within 15 min while in the S180 tumour lysosomal accumulation of the nuclide occurred over the first 24 h. Normal mouse liver showed a similar pattern to this latter tumour. It is postulated that these variations in the rate of lysosomal accumulation of ⁶⁷Ga reflect differences in the permeability of the lysosomal membrane. While large amounts of ⁶⁷Ga were found in the crude nuclear fraction of some tumours this was attributed to unbroken cells as studies with purified nuclei from 7 different tumours indicated that between 2 and 14% of the total tumour ⁶⁷Ga was associated with the nuclei.     

1-[<Superscript>11</Superscript>C]-acetate PET imaging in head and neck cancer—a comparison with <Superscript>18</Superscript>F-FDG-PET: implications for staging and radiotherapy planning

Purpose The aim of this study was to evaluate the feasibility of using 1-[¹¹C]-acetate positron emission tomography (ACE-PET) to detect and delineate the gross tumour volume of head and neck cancer before radiotherapy, and to compare the results with those obtained using ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) PET. Methods Ten patients with histologically verified squamous cell carcinoma were investigated by FDG-PET and dynamic ACE-PET prior to radiotherapy. The two scans were performed on the same day or on consecutive days, except in one patient in whom they were done 5 days apart. Diagnostic CT or MRI was performed in all patients. The image data sets were analysed both visually and semi-quantitatively. All primary tumours and metastases were delineated automatically by using the 50% threshold of maximum radioactivity corrected for background. The mean standardised uptake value (SUV) and the tumour volumes were evaluated and compared. Results All ten primary tumours were detected by ACE-PET, while nine primaries were detected by FDG-PET and CT and/or MRI. The ACE SUV tended to be lower than the FDG SUV (5.3±2.7 vs 9.6±7.0, p=0.07). The tumour volumes delineated with ACE were on average 51% larger than the FDG volumes (p<0.05). ACE-PET identified 20/21 lymph node metastases, while only 13/21 lesions were detected by FDG-PET and 16/21 lesions by CT or MRI. Conclusion ACE-PET appears promising for the staging of head and neck cancer. The biological information provided by both FDG and ACE must be carefully validated before it can be used in clinical routine for radiation treatment planning. More studies are needed to evaluate the differences in volumes and to confirm the clinical potential of both FDG and ACE-PET, especially in radiotherapy. The first two authors contributed equally to this paper.     

The optimum time for tumour imaging with thallium-201

Following the intravenous injection of 75 MBq ²⁰¹Tl-chloride we have assessed the uptake kinetics in the myocardium and in the primary tumour in 56 patients with lung cancer, 26 with breast cancer and 13 with mediastinal lymphoma. The time of maximal tumour uptake ranged from 8–20 min post-injection and did not differ significantly between lung cancer (mean±SD=11.9±3.34 min), breast cancer (11.21±1.88 min) and lymphoma (11.76±3.25 min). The time of maximum cardiac uptake of ²⁰¹Tl was 11.61±3.25 min. There was no significant washout of ²⁰¹Tl from the tumours in the first hour after injection in the various malignant lesions studied. The time of maximal tumour to background activity was 18.3±0.59 min for lung cancer, 13.0±1.16 min for breast cancer and 16.7±1.04 min for lymphoma.The time course of ²⁰¹Tl uptake in the tumours suggests that the mechanism of uptake is similar to that in the myocardium. The optimal time of ²⁰¹Tl tumour imaging is from 20–60 min following injection and did not differ in various tumours studied.